HK1116491A

HK1116491A - New heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists

Info

Publication number: HK1116491A
Application number: HK08106960.5A
Authority: HK
Inventors: Edwards Louise; Isaac Methvin; Johansson Martin; Kers Annika; Malmberg Johan; Mcleod Donald; Minidis Alexander; Staaf Karin; Slassi Abdelmalik; Stefanac Tomislav; Stormann Thomas; Wensbo David; Xin Tao; Arora Jalaj
Original assignee: Astrazeneca Ab
Priority date: 2004-02-18
Filing date: 2008-06-23
Publication date: 2008-12-24

Description

Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists

This application is a divisional application of a patent application entitled "novel heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists" with international application date being 15/2/2005 (international application number PCT/US2005/004774) and with national phase entry application number 200580004306.3.

Technical Field

[0001] The present invention relates to a novel class of compounds, pharmaceutical formulations comprising such compounds and the use of such compounds in therapy. The invention also relates to processes for preparing these compounds and to novel intermediates prepared therein.

Background

[0002] Glutamate is the major excitatory neurotransmitter in the mammalian Central Nervous System (CNS). Glutamate exerts its effects on central neurons by binding and subsequently activating cell surface receptors. These receptors are divided into two major classes, the ionized and metabotropic glutamate receptors, based on the structural characteristics of the receptor proteins, the manner in which they transduce signals into cells, and pharmacological characteristics.

[0003] Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors that activate a variety of intracellular second messenger systems upon binding to glutamate. Activation of mGluRs in intact mammalian neurons will elicit one or more of the following responses: activation of phospholipase C; enhanced inositol Phosphate (PI) hydrolysis; intracellular calcium release; activation of phospholipase D; activation or inhibition of adenylate cyclase; an increase or decrease in cyclic adenosine monophosphate (cAMP) formation; activation of ornithyl cyclase; an increase in cyclic guanosine monophosphate (cGMP) formation; activation of phospholipase a 2; an increase in arachidonic acid release; and an increase or decrease in potential or ligand-gated ion channel activity. Schoepp et al, Trends pharmacol. sci.14: 13(1993), Schoepp, neurohem. int.24: 439(1994), Pin et al Neuropharmacology 34: 1(1995), Bordi and Ugolini, Prog Neurobiol.59: 55.

[0004] Molecular cloning has identified eight distinct mGluR subtypes, designated mGlu1 through mGluR 8. Nakanishi, Neuron 13: 1031(1994), Pin et al Neuropharmacology 34: 1(1995), Knoppfel et al J.Med.chem.38: 1417(1995). Greater receptor diversity is generated by the expression of alternative conjugated forms of certain mGluR subtypes. Pin et al PNAS 89: 10331(1992), Minakami et al BBRC 199: 1136(1994), Joly et al J.Neurosci.15: 3970(1995).

[0005] Metabotropic glutamate receptors are subdivided into three groups, group I, group II and group III mGluRs, based on amino acid sequence homology, the second messenger system used by the receptors, and pharmacological properties. Group I mglurs include mGluR1, mGluR5, and their optionally conjugated variants. Binding of agonists to these receptors results in activation of phospholipase C and subsequent mobilization of intracellular calcium.

Neurological, psychiatric and pain disorders

[0006] Elucidation of the physiological role of group I mGluRs suggests that activation of these receptors causes neuronal excitation. Many studies have demonstrated that group I mGluRs agonists will be able to produce postsynaptic excitation once applied to neurons in the hippocampal plaques, cerebral cortex, cerebellum, thalamus and other central nervous regions. Evidence suggests that this predisposition is due to direct activation of postsynaptic mGluRs, but activation of presynaptic mGluRs has also been proposed to result in increased neurotransmitter release. Baskys, Trends pharmacol. sci.15: 92(1992), Schoepp, neurohem. int.24: 439(1994), Pin et al Neuropharmacology 34: 1(1995), Watkins et al Trends Pharmacol. Sci.15: 33(1994).

[0007] Metabotropic glutamate receptors are involved in many of the normal activities of the mammalian CNS. Activation of mGluRs has been shown to be essential for the induction of hippocampal plaque length-enhancing effects and cerebellar length-inhibiting effects. Bashir et al Nature 363: 347(1993), Bortolotto et al Nature 368: 740(1994), Aiba et al Cell 79: 365(1994), Aiba et al Cell 79: 377(1994). The role of mGluR activation in nociception and analgesia has also been demonstrated, Meller et al Neuroreport 4: 879(1993), Bordi and Ugolini, Brain Res.871: 223(1999). In addition, activation of mglurs has been suggested to play a regulatory role in a variety of other normal activities, including synaptic transmission, neuronal development, neuronal apoptosis, synaptic adaptation, spatial sensation, olfactory memory, central control of cardiac activity, alertness, motor control, and control of the vestibulo-ocular reflex. Nakanishi, Neuron 13: 1031(1994), Pin et al Neuropharmacology 34: 1, Knoppel et al J.Med.chem.38: 1417(1995).

[0008] Moreover, group I metabotropic glutamate receptors and mGluR5 are particularly implicated in playing a role in a variety of pathophysiological processes and disorders affecting the CNS. Including stroke, head trauma, hypoxic and ischemic injury, hypoglycemia, epilepsy, neurodegenerative diseases such as Alzheimer's disease and pain. Schoepp et al trends pharmacol. sci.14: 13(1993), Life Sci.54, Cunningham et al: 135(1994), Hollman et al ann.rev.neurosci.17: 31(1994), Pin et al Neuropharmacology 34: 1(1995), Knopfel et al J.Med chem.38: 1417(1995), zooren et al Trends Pharmacol sci.22: 331(2001), Gasparini et al curr. opin. pharmacol.2: 43(2002), Neugebauer Pain 98: 1(2002). Most of the pathologies in these disorders are believed to be due to glutamate-induced hyperexcitation of CNS neurons. Since group I mGluRs are able to increase glutamate-mediated neuronal excitation by postsynaptic mechanisms and by increasing presynaptic glutamate release, their activation may contribute to pathological conditions. Therefore, selective antagonists of group I mGluR receptors may be of therapeutic benefit, particularly as neuroprotective agents, analgesics, or anticonvulsants.

[0009] Recent advances in elucidating the neurophysiological roles of metabotropic glutamate receptors in general, and group I metabotropic glutamate receptors in particular, have established these receptors as promising drug targets in the treatment of acute and chronic neurological and psychiatric disorders, and chronic and acute pain conditions. Because of their physiological and pathophysiological importance, there is a need to develop new potent mGluR agonists and antagonists that are highly selective for mGluR subtypes, particularly the group I receptor subtype, and most particularly the mGluR5 subtype.

Gastrointestinal diseases

[0010] The Lower Esophageal Sphincter (LES) is prone to intermittent relaxation. The mechanical obstruction is temporarily eliminated at this time, with the result that gastric juices flow into the esophagus, hereinafter referred to as "gastrointestinal reflux".

[0011] Gastroesophageal reflux disease (GERD) is the most widespread upper gastrointestinal disorder. Current drug therapies are directed to reducing gastric acid secretion, or neutralizing acid in the esophagus. An important mechanism of gastrointestinal reflux is thought to be low lower esophageal sphincter tone. However, as Holloway & Dent (1990) gastroenterol. clin. n. amer.19, pages 517-535, it was shown that most reflux episodes are during Transient Lower Esophageal Sphincter Relaxations (TLESRs), i.e. relaxations not triggered by swallowing. It has also been shown that gastric secretion is generally normal in patients with GERD.

[0012] The novel compounds of the present invention can be used to inhibit Transient Lower Esophageal Sphincter Relaxations (TLESRs), thereby treating gastroesophageal reflux disease (GERD).

[0013] The word "TLESR" herein, transient lower esophageal sphincter relaxations, is in accordance with Mittal, r.k., Holloway, RH., Penagini, r., Blackshaw, l.a., Dent, j., 1995; gastroenterology 109, pages 601-610.

[0014] The term "gastrointestinal reflux" is defined herein as the flow of fluid out of the stomach into the esophagus, as the mechanical obstruction is temporarily eliminated.

[0015] The term "GERD" herein, gastroesophageal reflux disease, according to van heirwarden, m.a., Smout a.j.p.m., 2000; diagnosines of reflexie.Bailliere's Clin.gastroenterol.14, pages 759-774.

[0016] Because of their physiological and pathophysiological importance, there is a need to develop new potent mGluR agonists and antagonists that are highly selective for mGluR subtypes, particularly group I receptor subtypes.

[0017] It is an object of the present invention to provide compounds which are active at metabotropic glutamate receptors (mGluRs), particularly the mGluR5 receptor.

Summary of The Invention

[0018] The present invention provides compounds of formula Ia

Wherein:

[0019]p is selected from hydrogen, C_3-7An alkyl or a 3-8 membered ring comprising one or more atoms independently selected from C, N, O and S, which ring may optionally be fused to a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S;

[0020]R¹selected from: hydrogen, hydroxy, halogen, nitro, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_1-6Alkyl radical, OC_1-6Alkyl radical, C_2-6Alkenyl radical, OC_2-6Alkenyl radical, C_2-6Alkynyl, OC_2-6Alkynyl, C_0-6Alkyl radical C_3-6Cycloalkyl radical, OC_0-6Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl, OC_0-6Alkylaryl, CHO, (CO) R⁵，O(CO)R⁵，O(CO)OR⁵，O(CN)OR⁵，C_1-6Alkyl OR⁵，OC_2-6Alkyl OR⁵，C_1-6Alkyl (CO) R⁵，OC_1-6Alkyl (CO) R⁵，C_0-6Alkyl group CO₂R⁵，OC_1-6Alkyl group CO₂R⁵，C_0-6Alkylcyano, OC_2-6Alkylcyano radical, C_0-6Alkyl radical NR⁵R⁶，OC_2-6Alkyl radical NR⁵R⁶，C_1-6Alkyl (CO) NR⁵R⁶，OC_1-6Alkyl (CO) NR⁵R⁶，C_0-6Alkyl radical NR⁵(CO)R⁶，OC_2-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)NR⁵R⁶，C_0-6Alkyl SR⁵，OC_2-6Alkyl SR⁵，C_0-6Alkyl (SO) R⁵，OC_2-6Alkyl (SO) R⁵，C_0-6Alkyl SO₂R⁵，OC_2-6Alkyl SO₂R⁵，C_0-6Alkyl (SO)₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)NR⁵R⁶，C_0-6Alkyl radical NR⁵(SO₂)R⁶，OC_2-6Alkyl radical NR⁵(SO₂)R⁶，C_0-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，OC_2-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，(CO)NR⁵R⁶，O(CO)NR⁵R⁶，NR⁵OR⁶，C_0-6Alkyl radical NR⁵(CO)OR⁶，OC_2-6Alkyl radical NR⁵(CO)OR⁶，SO₃R⁵And a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S, wherein the ring may be substituted with one or more A;

[0021]M¹selected from the group consisting of a bond, C_1-3Alkyl radical, C_2-3Alkenyl radical, C_2-3Alkynyl, C_0-4Alkyl (CO) C_0-4Alkyl radical, C_0-3Alkyl OC_0-3Alkyl radical, C _0-3Alkyl (CO) NR⁵，C_0-3Alkyl (CO) NR⁵C_0-3Alkyl radical, C_0-4Alkyl radical NR⁵，C_0-3Alkyl group SC_0-3Alkyl radical, C_0-3Alkyl (SO) C_0-3Alkyl or C_0-3Alkyl (SO)₂)C_0-3An alkyl group;

[0022]R²selected from hydrogen, hydroxy, C_0-6Alkyl cyano, oxo, ═ NR⁵，＝NOR⁵，C_1-4Alkyl halides, halogens, C_1-4Alkyl, O (CO) C_1-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, OC_1-4Alkyl radical, C_1-4Alkyl radicalOR⁵And C_0-4Alkyl radical NR⁵R⁶；

[0023]X¹、X²And X³Independently selected from CR, CO, N, NR, O and S;

[0024]r is selected from hydrogen, C_0-3Alkyl, halogen, C_0-3Alkyl OR⁵，C_0-3Alkyl radical NR⁵R⁶，C_0-3Alkyl (CO) OR⁵，C_0-3Alkyl radical NR⁵R⁶And C_0-3An alkylaryl group;

[0025]M²selected from the group consisting of a bond, C_1-3Alkyl radical, C_3-7Cycloalkyl radical, C_2-3Alkenyl radical, C_2-3Alkynyl, C_0-4Alkyl (CO) C_0-4Alkyl radical, C_0-3Alkyl OC_0-3Alkyl radical, C_0-3Alkyl radical NR⁵C_1-3Alkyl radical, C_0-3Alkyl (CO) NR⁵，C_0-4Alkyl radical NR⁵，C_0-3Alkyl group SC_0-3Alkyl radical, C_0-3Alkyl (SO) C_0-3Alkyl and C_0-3Alkyl (SO)₂)C_0-3An alkyl group;

[0026]R³selected from hydrogen, hydroxy, C_0-6Alkyl cyano, oxo, ═ NR⁵，＝NOR⁵，C_1-4Alkyl halides, halogens, C_1-4Alkyl, O (CO) C_1-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, OC_1-4Alkyl radical, C_1-4Alkyl OR⁵And C_0-4Alkyl radical NR⁵R⁶；

[0027]X⁴Selected from: c_0-4Alkyl radical R⁵，C_0-4Alkyl (NR)⁵R⁶)，C_0-4Alkyl (NR)⁵R⁶)＝N，NR⁵C_0-4Alkyl (NR)⁵R⁶)＝N，NOC_0-4Alkyl radical, C_1-4Alkyl halides, C, O, SO，SO₂And S;

[0028] q is a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S, wherein the groups are optionally fused to a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S, which fused ring may be substituted with one or more a;

[0029]R⁴Selected from: hydrogen, hydroxy, C_0-6Alkyl cyano, oxo, ═ NR⁵，＝NOR⁵，C_1-4Alkyl halides, halogens, C_1-4Alkyl radical, OC_1-4Alkyl radical, OC_0-6Alkylaryl, O (CO) C_1-4Alkyl radical, C_0-4Alkyl (S) C_0-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, C_1-4Alkyl OR⁵，C_0-4Alkyl radical NR⁵R⁶And a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O or S, wherein the ring may be substituted with one or more A;

[0030]R⁵and R⁶Independently selected from: hydrogen, hydroxy, C_1-6Alkyl radical, C_0-6Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl group, C_0-6An alkylheteroaryl group and a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S, wherein R is⁵And R⁶May together form a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S;

[0031]wherein any one R¹、R²、R³、R⁴、R⁵And R⁶C under definition_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_2-6Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl and C_0-6The alkylheteroaryl groups may all be substituted by one or more a;

[0032]a is selected from: hydrogen, hydroxy, oxo, halogenNitro radical, C_0-6Alkylcyano radical, C_1-4Alkyl radical, C_0-4Alkyl radical C_3-6Cycloalkyl radical, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_2-6Alkenyl radical, OC_1-6Alkyl radical, C_0-3Alkylaryl group, C_0-6Alkyl OR ⁵，OC_2-6Alkyl OR⁵，C_1-6Alkyl SR⁵，OC_2-6Alkyl SR⁵，(CO)R⁵，O(CO)R⁵，OC_2-6Alkylcyano radical, C_0-6Alkyl group CO₂R⁵，OC_1-6Alkyl group CO₂R⁵，O(CO)OR⁵，OC_1-6Alkyl (CO) R⁵，C_1-6Alkyl (CO) R⁵，NR⁵OR⁶，C_0-6Alkyl radical NR⁵R⁶，OC_2-6Alkyl radical NR⁵R⁶，C_0-6Alkyl (CO) NR⁵R⁶，OC_1-6Alkyl (CO) NR⁵R⁶，OC_2-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)NR⁵R⁶，O(CO)NR⁵R⁶，NR⁵(CO)OR⁶，C_0-6Alkyl (SO)₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)NR⁵R⁶，C_0-6Alkyl radical NR⁵(SO₂)R⁶，OC_2-6Alkyl radical NR⁵(SO₂)R⁶，SO₃R⁵，C_1-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)R⁵，C_0-6Alkyl (SO)₂)R⁵，C_0-6Alkyl (SO) R⁵，OC_2-6Alkyl (SO) R⁵And a 5 or 6 membered ring comprising one or more atoms independently selected from C, N, O and S;

[0033] m is selected from 0, 1, 2, 3 and 4; and is

[0034] n is selected from 0, 1, 2 and 3,

[0035] or a salt thereof.

[0036] The present invention provides compounds of formula I

Wherein

[0037] P is selected from thienyl, pyridyl, thiazolyl, furyl, pyrrolyl and phenyl wherein the phenyl ring is substituted in the 3 position or disubstituted in the 2 and 5 positions;

[0038]R¹attached to P via a carbon atom of the P ring, R¹Selected from: hydrogen, hydroxy, halogen, nitro, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_1-6Alkyl radical, OC_1-6Alkyl radical, C_2-6Alkenyl radical, OC_2-6Alkenyl radical, C_2-6Alkynyl, OC_2-6Alkynyl, C_0-6Alkyl radical C_3-6Cycloalkyl radical, OC_0-6Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl, OC_0-6Alkylaryl, CHO, (CO) R⁵，O(CO)R⁵，O(CO)OR⁵，O(CN)OR⁵，C_1-6Alkyl OR⁵，OC_2-6Alkyl OR⁵，C_1-6Alkyl (CO) R⁵，OC_1-6Alkyl (CO) R⁵，C_0-6Alkyl group CO₂R⁵，OC_1-6Alkyl group CO₂R⁵，C_0-6Alkylcyano, OC_2-6Alkylcyano radical, C_0-6Alkyl radical NR⁵R⁶，OC_2-6Alkyl radical NR⁵R⁶，C_1-6Alkyl (CO) NR⁵R⁶，OC_1-6Alkyl (CO) NR ⁵R⁶，C_0-6Alkyl radical NR⁵(CO)R⁶，OC_2-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)NR⁵R⁶，C_0-6Alkyl SR⁵，OC_2-6Alkyl SR⁵，C_0-6Alkyl radical(SO)R⁵，OC_2-6Alkyl (SO) R⁵，C_0-6Alkyl SO₂R⁵，OC_2-6Alkyl SO₂R⁵，C_0-6Alkyl (SO)₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)NR⁵R⁶，C_0-6Alkyl radical NR⁵(SO₂)R⁶，OC_2-6Alkyl radical NR⁵(SO₂)R⁶，C_0-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，OC_2-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，(CO)NR⁵R⁶，O(CO)NR⁵R⁶，NR⁵OR⁶，C_0-6Alkyl radical NR⁵(CO)OR⁶，OC_2-6Alkyl radical NR⁵(CO)OR⁶，SO₃R⁵And a 5 or 6 membered ring comprising one or more atoms independently selected from C, N, O and S;

[0039]M¹is a bond;

[0040]X¹selected from C, CO, N, O and S;

[0041]X²selected from C, N, O and S;

[0042]X³is i) selected from N, O and S, or

[0043]ii) when X²Selected from N, O or X at S³Selected from N, O, S and C, and when X³When is C, X³The substituent R on (A) is H;

[0044]r is selected from hydrogen, C_0-3Alkyl, halogen, C_0-3Alkyl OR⁵，C_0-3Alkyl radical NR⁵R⁶，C_0-3Alkyl (CO) OR⁵And C_0-3An alkylaryl group;

[0045]M²selected from the group consisting of a bond, C_1-3Alkyl radical, C_2-3Alkynyl, C_0-4Alkyl (CO) C_0-4Alkyl radical, C_0-3Alkyl OC_0-3Alkyl radical, C_0-3Alkyl radical NR⁵C_1-3Alkyl radical, C_0-3Alkyl (CO) NR⁵，C_0-4Alkyl radical NR⁵，C_0-3Alkyl (SO) C_0-3Alkyl and C_0-3Alkyl (SO)₂)C_0-3An alkyl group;

[0046]R³selected from hydroxy, C_0-6Alkyl cyano, oxo, ═ NR⁵，＝NOR⁵，C_1-4Alkyl halides, halogens, C_1-4Alkyl, O (CO) C_1-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, OC_1-4Alkyl radical, C_1-4Alkyl OR⁵And C_0-4Alkyl radical NR⁵R⁶；

[0047]X⁴Is selected from C_0-4Alkyl radical R⁵R⁶，C_3-7Cycloalkyl radical, C_1-4Alkyl (NR)⁵R⁶)，NR⁵，C_0-4Alkyl (NR)⁵R⁶)＝N，NR⁵C_0-4Alkyl (NR)⁵R⁶)＝N，NOC_0-4Alkyl radical, C_1-4Alkyl halo, O, SO₂And S, wherein M²And X⁴The bond in between is a single bond;

[0048]q is i) selected from triazolyl, imidazolyl, oxadiazolyl, imidazolinonyl, oxazolonyl, thiazolonyl, tetrazolyl and thiadiazolyl, wherein any substitutable nitrogen atom in the ring is substituted on said nitrogen atom by R ⁴Substituted, any suitable carbon atom being optionally substituted by R⁴Substitution; and is

[0049]R⁴Selected from: c_0-6Alkyl cyano, ═ NC_1-4Alkyl, ═ NOR⁵，C_1-4Alkyl halides, halogens, C_1-6Alkyl radical, OC_1-4Alkyl radical, C_2-4Alkenyl radical, C_0-2Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl group, C_0-6Alkylheteroaryl, OC_0-6Alkylaryl, OC_0-6Alkyl heteroaromatic compoundsBase, NC_0-6Alkylaryl, NC_0-6Alkyl heteroaryl radical, C_0-6Alkyl Oaryl, C_0-6Alkyl O heteroaryl, C_0-6alkyl-N-aryl, C_0-6Alkyl N heteroaryl, OC_0-6Alkyl Oaryl, OC_0-6Alkyl O heteroaryl, OC_0-6Alkyl N aryl, OC_0-6Alkyl N heteroaryl, NC_0-6Alkyl Oaryl, NC_0-6Alkyl O heteroaryl, NC_0-6alkyl-N-aryl, NC_0-6Alkyl N heteroaryl, O (CO) C_1-4Alkyl radical, C_0-4Alkyl (CO) OC_1-4Alkyl radical, C_1-4Alkyl (S) C_0-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, C_1-4Alkyl OR⁵，C_0-4Alkyl radical N (C)_1-4Alkyl radical)₂And a 3-or 6-membered non-aromatic ring comprising one or more atoms independently selected from C, N, O and S, which ring may optionally be fused to a 5-membered ring comprising one or more atoms independently selected from C, N and O, wherein said ring and said fused ring may be substituted with one or two A; or

[0050] ii) is selected from benzimidazolyl, benzoxazolyl, tetrahydrotriazolopyridinyl, tetrahydrotriazolopyrimidinyl, pyridonyl, pyridazinyl, imidazopyridinyl, oxazolopyridyl, thiazolopyridyl, imidazopyridazinyl, oxazolopyridazinyl, thiazolopyridazinyl and purinyl; and is

[0051]R⁴Selected from: hydrogen, hydroxy, C_0-6Alkyl cyano, ═ NR⁵，＝NOR⁵，C_1-4Alkyl halides, halogens, C_1-6Alkyl radical, OC_1-4Alkyl radical, OC_0-6Alkylaryl, O (CO) C_1-4Alkyl radical, C_0-4Alkyl (S) C_0-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, C_1-4Alkyl OR⁵，C_0-4Alkyl radical NR⁵R⁶And a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O or S, which ring may optionally be fused to a 5-or 6-membered ring comprising one or more atoms selected from C, N and O, said ring and said fused ring may be substituted with one or two A;

[0052]R⁵and R⁶Independently selected from hydrogen and C_1-6An alkyl group; wherein R is¹、R²And R⁴Any C defined in (1)_1-6Alkyl groups may each be substituted by one or more a;

[0053]a is selected from: hydrogen, hydroxy, halogen, nitro, oxo, C_0-6Alkylcyano radical, C_0-4Alkyl radical C_3-6Cycloalkyl radical, C_1-6Alkyl radical, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_2-6Alkenyl radical, C_0-3Alkylaryl group, C_0-6Alkyl OR⁵，OC_2-6Alkyl OR⁵，C_1-6Alkyl SR⁵，OC_2-6Alkyl SR⁵，(CO)R⁵，O(CO)R⁵，OC_2-6Alkylcyano, OC_1-6Alkyl group CO₂R⁵，O(CO)OR⁵，OC_1-6Alkyl (CO) R⁵，C_1-6Alkyl (CO) R⁵，NR⁵OR⁶，OC_2-6Alkyl radical NR⁵R⁶，C_0-6Alkyl (CO) NR⁵R⁶，OC_1-6Alkyl (CO) NR⁵R⁶，OC_2-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)NR⁵R⁶，O(CO)NR⁵R⁶，C_0-6Alkyl (SO)₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)NR⁵R⁶，C_0-6Alkyl radical NR⁵(SO₂)R⁶，OC_0-6Alkyl radical NR⁵(SO₂)R⁶，SO₃R⁵，C_1-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)R⁵，C_0-6Alkyl (SO)₂)R⁵，C_0-6Alkyl (SO) R⁵，OC_2-6Alkyl (SO) R⁵And a 5-membered ring comprising one or more atoms independently selected from C, N, O and S;

[0054] m1 is selected from 0, 1, 2, 3 and 4;

[0055] m2 is selected from 0, 1, 2 and 3;

[0056] n is selected from 0, 1 and 2; and is

[0057] t is 0 or 1 and t is a linear or branched,

[0058] or a salt thereof,

[0059] with the proviso that the compound is not 5- (4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-thiophen-3-yl- [1, 2, 4] oxadiazole, 1, 2-bis {2- (3-amino-phenyl) - [1, 3, 4] oxadiazolyl) ethane, 1, 2-bis {5- [5- (4-nitro-phenyl) furan-2-yl ] - [1, 3, 4] oxadiazol-yl) ethane, 1, 2-bis {5- [5- (4-bromo-phenyl) furan-2-yl ] - [1, 3, 4] oxadiazol-yl) ethane, 1, 2-bis {5- [5- (4-chloro-phenyl) furan-2- -yl ] - [1, 3, 4] oxadiazol-yl) ethane and 1, 2-bis {5- [5- (2-, 4-dibromo-phenyl) furan-2-yl ] - [1, 3, 4] oxadiazol-yl) ethane.

[0060] The present invention provides compounds of formula Ib

Wherein

[0061] P is selected from thienyl, pyridyl, thiazolyl, furyl, pyrrolyl and phenyl wherein the phenyl ring is substituted in the 3 position or disubstituted in the 2 and 5 positions;

[0062]R¹attached to P via a carbon atom of the P ring, R¹Selected from: hydrogen, hydroxy, halogen, nitro, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_1-6Alkyl radical, OC_1-6Alkyl radical, C_2-6Alkenyl radical, OC_2-6Alkenyl radical, C_2-6Alkynyl, OC _2-6Alkynyl, C_0-6Alkyl radical C_3-6Cycloalkyl radical, OC_0-6Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl, OC_0-6Alkylaryl, CHO, (CO) R⁵，O(CO)R⁵，O(CO)OR⁵，O(CN)OR⁵，C_1-6Alkyl OR⁵，OC_2-6Alkyl OR⁵，C_1-6Alkyl (CO) R⁵，OC_1-6Alkyl (CO) R⁵，C_0-6Alkyl group CO₂R⁵，OC_1-6Alkyl group CO₂R⁵，C_0-6Alkylcyano, OC_2-6Alkylcyano radical, C_0-6Alkyl radical NR⁵R⁶，OC_2-6Alkyl radical NR⁵R⁶，C_1-6Alkyl (CO) NR⁵R⁶，OC_1-6Alkyl (CO) NR⁵R⁶，C_0-6Alkyl radical NR⁵(CO)R⁶，OC_2-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)NR⁵R⁶，C_0-6Alkyl SR⁵，OC_2-6Alkyl SR⁵，C_0-6Alkyl (SO) R⁵，OC_2-6Alkyl (SO) R⁵，C_0-6Alkyl SO₂R⁵，OC_2-6Alkyl SO₂R⁵，C_0-6Alkyl (SO)₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)NR⁵R⁶，C_0-6Alkyl radical NR⁵(SO₂)R⁶，OC_2-6Alkyl radical NR⁵(SO₂)R⁶，C_0-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，OC_2-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，(CO)NR⁵R⁶，O(CO)NR⁵R⁶，NR⁵OR⁶，C_0-6Alkyl radical NR⁵(CO)OR⁶，OC_2-6Alkyl radical NR⁵(CO)OR⁶，SO₃R⁵And a 5 or 6 membered ring comprising one or more atoms independently selected from C, N, O and S;

[0063]M¹is a bond;

[0064]X¹selected from C, CO, N, O and S;

[0065]X²selected from C, N, O and S;

[0066]X³selected from N, O and S, or when X is²N, O or X at S³Is CH;

[0067]r is selected from hydrogen, C_0-3Alkyl, halogen, C_0-3Alkyl OR⁵，C_0-3Alkyl radical NR⁵R⁶，C_0-3Alkyl (CO) OR⁵And C_0-3An alkylaryl group;

[0068]M²selected from the group consisting of a bond, C_1-3Alkyl radical, C_2-3Alkynyl, C_0-4Alkyl (CO) C_0-4Alkyl radical, C_0-3Alkyl OC_0-3Alkyl radical, C_0-3Alkyl radical NR⁵C_1-3Alkyl radical, C_0-3Alkyl (CO) NR⁵，C_0-4Alkyl radical NR⁵，C_0-3Alkyl (SO) C_0-3Alkyl and C_0-3Alkyl (SO)₂)C_0-3An alkyl group;

[0069]R³selected from hydroxy, C_0-6Alkyl cyano, oxo, ═ NR⁵，＝NOR⁵，C_1-4Alkyl halides, halogens, C_1-4Alkyl, O (CO) C_1-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, OC_1-4Alkyl radical, C _1-4Alkyl OR⁵And C_0-4Alkyl radical NR⁵R⁶；

[0070]X⁴Is selected from C_0-4Alkyl radical R⁵R⁶，C_3-7Cycloalkyl radical, C_1-4Alkyl (NR)⁵R⁶)，NR⁵，C_0-4Alkyl (NR)⁵R⁶)＝N，NR⁵C_0-4Alkyl (NR)⁵R⁶)＝N，NOC_0-4Alkyl radical, C_1-4Alkyl halo, O, SO₂And S, wherein M²And X⁴The bond in between is a single bond;

[0071]q is i) selected from triazolyl, imidazolyl, oxadiazolyl, imidazolinonyl, oxazolonyl, thiazolonyl, tetrazolyl and thiadiazolyl, wherein any substitutable nitrogen atom in the ring is substituted on said nitrogen atom by R⁴Substitution; and is

[0072]R⁴Selected from: c_0-6Alkyl cyano, ═ NC_1-4Alkyl, ═ NOR⁵，C_1-4Alkyl halides, halogens, C_1-6Alkyl radical, OC_1-4Alkyl radical, C_2-4Alkenyl radical, C_0-2Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl group, C_0-6Alkylheteroaryl, OC_0-6Alkylaryl, OC_0-6Alkylheteroaryl, NC_0-6Alkylaryl, NC_0-6Alkyl heteroaryl radical, C_0-6Alkyl Oaryl, C_0-6Alkyl O heteroaryl, C_0-6alkyl-N-aryl, C_0-6Alkyl N heteroaryl, OC_0-6Alkyl Oaryl, OC_0-6Alkyl O heteroaryl, OC_0-6Alkyl N aryl, OC_0-6Alkyl N heteroaryl, NC_0-6Alkyl Oaryl, NC_0-6Alkyl O heteroaryl, NC_0-6alkyl-N-aryl, NC_0-6Alkyl N heteroaryl, O (CO) C_1-4Alkyl radical, C_0-4Alkyl (CO) OC_1-4Alkyl radical, C_1-4Alkyl (S) C_0-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, C_1-4Alkyl OR⁵，C_0-4Alkyl radical N (C)_1-4Alkyl radical)₂Or a 3-or 6-membered non-aromatic ring comprising one or more atoms independently selected from C, N, O and S, which ring may optionally be fused to a 5-membered ring comprising one or more atoms independently selected from C, N and O, Wherein said rings and said fused rings may be substituted by one or two A; or

[0073] ii) is selected from benzimidazolyl, benzoxazolyl, tetrahydrotriazolopyridinyl, tetrahydrotriazolopyrimidinyl, pyridonyl, pyridazinyl, imidazopyridinyl, oxazolopyridyl, thiazolopyridyl, imidazopyridazinyl, oxazolopyridazinyl, thiazolopyridazinyl and purinyl; and is

[0074]R⁴Selected from: hydrogen, hydroxy, C_0-6Alkyl cyano, ═ NR⁵，＝NOR⁵，C_1-4Alkyl halides, halogens, C_1-6Alkyl radical, OC_1-4Alkyl radical, OC_0-6Alkylaryl, O (CO) C_1-4Alkyl radical, C_0-4Alkyl (S) C_0-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, C_1-4Alkyl OR⁵，C_0-4Alkyl radical NR⁵R⁶And a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O or S, which ring may optionally be fused to a 5-or 6-membered ring comprising one or more atoms independently selected from C, N and O, wherein said ring and said fused ring may be substituted with one or two A;

[0075]R⁵and R⁶Independently selected from hydrogen and C_1-6An alkyl group;

[0076]wherein R is¹、R²And R⁴Any C defined in (1)_1-6Alkyl groups may each be substituted by one or more a;

[0077]a is selected from: hydrogen, hydroxy, halogen, nitro, oxo, C_0-6Alkylcyano radical, C _0-4Alkyl radical C_3-6Cycloalkyl radical, C_1-6Alkyl radical, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_2-6Alkenyl radical, C_0-3Alkylaryl group, C_0-6Alkyl OR⁵，OC_2-6Alkyl OR⁵，C_1-6Alkyl SR⁵，OC_2-6Alkyl SR⁵，(CO)R⁵，O(CO)R⁵，OC_2-6Alkylcyano, OC_1-6Alkyl group CO₂R⁵，O(CO)OR⁵，OC_1-6Alkyl (CO) R⁵，C_1-6Alkyl (CO) R⁵，NR⁵OR⁶，OC_2-6Alkyl radical NR⁵R⁶，C_0-6Alkyl (CO) NR⁵R⁶，OC_1-6Alkyl (CO) NR⁵R⁶，OC_2-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)NR⁵R⁶，O(CO)NR⁵R⁶，C_0-6Alkyl (SO)₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)NR⁵R⁶，C_0-6Alkyl radical NR⁵(SO₂)R⁶，OC_2-6Alkyl radical NR⁵(SO₂)R⁶，SO₃R⁵，C_1-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)R⁵，C_0-6Alkyl (SO)₂)R⁵，C_0-6Alkyl (SO) R⁵，OC_2-6Alkyl (SO) R⁵And a 5-membered ring comprising one or more atoms independently selected from C, N, O and S;

[0078] m1 is selected from 0, 1, 2, 3 and 4;

[0079] m2 is selected from 0, 1, 2 and 3;

[0080] n is selected from 0, 1 and 2; and is

[0081] t is 0 or 1 and t is a linear or branched,

[0082] or a salt thereof,

[0083] with the proviso that the compound is not 5- (4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-thiophen-3-yl- [1, 2, 4] oxadiazole.

[0084] In another aspect of the invention there is provided a pharmaceutical formulation comprising a therapeutically effective amount of a compound of formula I and a pharmaceutically acceptable carrier.

[0085] In a further aspect of the invention there is provided a pharmaceutical formulation comprising a compound of formula I for use in the treatment of mGluR5 receptor mediated disorders, in particular neurological disorders, psychiatric disorders, acute and chronic pain and gastrointestinal disorders.

[0086] In yet another aspect of the invention, there is provided a compound of formula I for use in the treatment of mGluR5 receptor mediated disorders, in particular neurological disorders, psychiatric disorders, acute and chronic pain, and gastrointestinal disorders.

[0087] In another aspect, the invention provides methods for preparing compounds of formula I, as well as intermediates produced therein.

[0088] These and other aspects of the invention are described in more detail below.

Detailed Description

[0089] Listed below are definitions of various terms used in the specification and claims to describe the present invention.

[0090] If a group is defined herein as "previously defined", "having the same definition as" or "having the same definition as" above ", then, to avoid ambiguity, the group should be understood as encompassing the first occurrence and the broadest definition as well as each and every other definition that applies to the group.

[0091]For the avoidance of doubt, "C" in this specification_1-6"should be understood to mean a carbon group having 1, 2, 3, 4, 5 or 6 carbon atoms.

[0092] In the present specification, "C" represents 1 carbon atom.

[0093] Unless otherwise indicated, the term "alkyl" in this specification includes straight and branched chain alkyl groups, which may be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,

[0094]sec-butyl, tert-butyl, n-pentylIsopentyl, tert-amyl, neopentyl, n-hexyl or isohexyl, tert-hexyl. The term "C _1-3Alkyl "refers to an alkyl group having 1, 2 or 3 carbon atoms and may be methyl, ethyl, n-propyl and isopropyl.

[0095]In this specification, unless otherwise specified, the term "cycloalkyl" refers to an optionally substituted saturated cyclic hydrocarbon ring system. The term "C_3-7Cycloalkyl "may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

[0096]In this specification, unless otherwise specified, the term "alkenyl" includes straight-chain and branched alkenyl groups. The term "C_2-6The alkenyl group "means an alkenyl group having 2 to 6 carbon atoms and 1 or 2 double bonds, and may be, but is not limited to, vinyl, allyl, propenyl, isopropenyl, butenyl, isobutenyl, 2-butenyl, pentenyl, isopentenyl, and hexenyl.

[0097]In this specification, unless otherwise specified, the term "alkynyl" includes straight and branched chain alkynyl groups. Term C_2-6Alkynyl has 2 to 6 carbon atoms and 1 or 2 triple bonds and may be, but is not limited to, ethynyl, propargyl, butynyl, isobutynyl, pentynyl, isopentynyl, and hexynyl.

[0098] The term "aryl" refers to an optionally substituted monocyclic or bicyclic hydrocarbon ring system containing at least one unsaturated aromatic ring. Examples of the term "aryl" and suitable options are phenyl, naphthyl, 1, 2, 3, 4-tetrahydronaphthyl, indolyl and indenyl.

[0099] In this specification, unless otherwise indicated, the term "heteroaryl" refers to an optionally substituted monocyclic or bicyclic unsaturated aromatic ring system containing at least one heteroatom independently selected from N, O or S. Examples of "heteroaryl" may be, but are not limited to, thiophene, pyridine, thiazole, furan, pyrrole, triazole, imidazole, oxadiazole, oxazole, isoxazole, pyrazole, imidazolinone, oxazolone, thiazolone, tetrazolyl and thiadiazolyl, benzimidazole, benzoxazolyl, tetrahydrotriazolopyridine, tetrahydrotriazolopyrimidine, benzofuranyl, indole, isoindol, pyridone, pyridazinyl, pyrimidinyl, imidazopyridine, oxazolopyridine, thiazolopyridine, pyridine, imidazopyridazinyl, oxazolopyridazinyl, thiazolopyridazinyl, and purinyl.

[0100] In this specification, unless otherwise specified, the terms "alkylaryl", "alkylheteroaryl" and "alkylcycloalkyl" refer to a substituent attached to an aryl, heteroaryl and cycloalkyl group through an alkyl group.

[0101] In this specification, unless otherwise specified, 5-or 6-membered rings containing one or more atoms independently selected from C, N, O or S include aromatic and heteroaromatic rings and saturated or unsaturated carbocyclic and heterocyclic rings. Examples of such rings include, but are not limited to, furyl, isoxazolyl, isothiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, thiazolyl, thienyl, imidazolyl, imidazolidinyl, imidazolinyl, triazolyl, morpholinyl, piperazinyl, piperidinyl, piperidinonyl, pyrazolidinyl, pyrazolinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, thiomorpholinyl, phenyl, cyclohexyl, cyclopentyl, and cyclohexenyl.

[0102] In this specification, unless otherwise specified, 3-to 8-membered rings containing one or more atoms independently selected from C, N, O or S include aromatic and heteroaromatic rings and saturated or unsaturated carbocyclic and heterocyclic rings. Examples of such rings may be, but are not limited to, imidazolidinyl, imidazolinyl, morpholinyl, piperazinyl, piperidinyl, piperidonyl, pyrazolidinyl, pyrazolinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl or thiomorpholinyl, tetrahydrothiopyranyl, furanyl, pyrrolyl, isoxazolyl, isothiazolyl, oxazolyl, oxazolidinonyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, thienyl, imidazolyl, triazolyl, phenyl, cyclopropyl, aziridinyl, cyclobutyl, azetidinyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctenyl, and cyclooctenyl.

[0103] In this specification, unless otherwise specified, 3 to 8 membered rings containing one or more atoms independently selected from C, N, O or S and which may optionally be fused to a 5 or 6 membered ring containing one or more atoms independently selected from C, N, O or S include aromatic and heteroaromatic rings and saturated or unsaturated carbocyclic and heterocyclic rings. Examples of such rings include, but are not limited to, naphthyl, norcareyl, chromyl, isochromoyl, indanyl, benzimidazolyl or tetrahydronaphthyl, benzoxazolyl, benzothiazolyl, benzofuranyl, benzothienyl, benzotriazolyl, indolyl, azaindolyl, indazolyl, indolinyl, isoindolinyl, benzimidazolyl, oxadiazolyl, thiadiazolyl, quinolinyl, quinoxalinyl and benzotriazolyl.

[0104]In this specification, unless otherwise specified, the term "═ NR⁵Or⁵"includes having R⁵The substituted imine and oxime groups may be, or partially may be, but are not limited to, groups including iminoalkyl, iminohydroxy, iminoalkoxy, amidine, hydroxyamidine, and alkoxyamidine.

[0105] When a subscript is an integer of 0, the groups indicated by the subscript indicate that the groups are absent, i.e., the groups are connected by a direct bond.

[0106] In the present specification, unless otherwise specified, the term "bond" is a saturated bond.

[0107] In this specification, unless otherwise specified, the term "halogen" may be fluorine, chlorine, bromine or iodine.

[0108]In this specification, unless otherwise indicated, the term "alkylhalo" means that the alkyl group defined above is substituted with one or more halogens. The term "C_1-6Alkyl halo "may include, but is not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl and bromopropylAnd (4) a base. The term "OC_1-6Alkyl halo "may include, but is not limited to, fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, and difluoroethoxy.

[0109]In one embodiment of the invention, P may be hydrogen or C _3-7Alkyl or P may be a 3-8 membered ring containing one or more atoms selected from C, N, O or S, which ring may optionally be fused to a 5-or 6-membered ring containing one or more atoms independently selected from C, N, O or S. In a preferred embodiment of the invention P is selected from 5-or 6-membered aromatic and heteroaromatic rings.

[0110] In a further preferred embodiment, P is selected from thiophene, pyridyl, thiazolyl, furyl, pyrrolyl and phenyl, wherein the phenyl ring is substituted in the 3-position or disubstituted in the 2-and 5-positions.

[0111] In a further preferred embodiment of the invention P is phenyl substituted in position 3 or phenyl disubstituted in positions 2 and 5.

[0112]P is optionally via a radical carrying 0, 1, 2, 3 or 4 radicals R¹Wherein R on the P ring¹The number of substituents is designated by the term m 1. In a preferred embodiment of the invention m1 is 1 or 2. In a further preferred embodiment of the invention m1 is 1.

[0113]In a suitable embodiment of the invention R¹Selected from: hydrogen, hydroxy, halogen, nitro, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_1-6Alkyl radical, OC_1-6Alkyl radical, C_2-6Alkenyl radical, OC_2-6Alkenyl radical, C_2-6Alkynyl, OC_2-6Alkynyl, C_0-6Alkyl radical C_3-6Cycloalkyl radical, OC_0-6Alkyl radical C_3-6Cycloalkyl radical, C _0-6Alkylaryl, OC_0-6Alkylaryl, CHO, (CO) R⁵，O(CO)R⁵，O(CO)OR⁵，O(CN)OR⁵，C_1-6Alkyl OR⁵，OC_2-6Alkyl OR⁵，C_1-6Alkyl (CO) R⁵，OC_1-6Alkyl (CO) R⁵，C_0-6Alkyl group CO₂R⁵，OC_1-6Alkyl group CO₂R₅，C_0-6Alkylcyano, OC_2-6Alkylcyano radical, C_0-6Alkyl radical NR⁵R⁶，OC_2-6Alkyl radical NR⁵R⁶，C_1-6Alkyl (CO) NR⁵R⁶，OC_1-6Alkyl (CO) NR⁵R⁶，C_0-6Alkyl radical NR⁵(CO)R⁶，OC_2-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)NR⁵R⁶，C_0-6Alkyl SR⁵，OC_2-6Alkyl SR⁵，C_0-6Alkyl (SO) R⁵，OC_2-6Alkyl (SO) R⁵，C_0-6Alkyl SO₂R⁵，OC_2-6Alkyl SO₂R⁵，C_0-6Alkyl (SO)₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)NR⁵R⁶，C_0-6Alkyl radical NR⁵(SO₂)R⁶，OC_2-6Alkyl radical NR⁵(SO₂)R⁶，C_0-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，OC_2-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，(CO)NR⁵R⁶，O(CO)NR⁵R⁶，NR⁵OR⁶，C_0-6Alkyl radical NR⁵(CO)OR⁶，OC_2-6Alkyl radical NR⁵(CO)OR⁶，SO₃R⁵And a 5 or 6 membered ring comprising one or more atoms independently selected from C, N, O and S.

[0114]In a more suitable embodiment of the invention R¹Selected from: hydrogen, hydroxy, halogen, nitro, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_1-6Alkyl radical, OC_1-6Alkyl radical, C_2-6Alkenyl radical, C_0-6Alkyl radical C_3-6Cycloalkyl radical, C_1-6Alkyl OR⁵，C_1-6Alkyl (CO) R⁵，C_0-6Alkyl group CO₂R⁵，C_0-6Alkylcyano radical, C_0-6Alkyl radical NR⁵R⁶，C_0-6Alkyl SR⁵And a 5-or 6-membered ring comprising one or more atoms independently selected from C and O.

[0115]R¹Any C under definition_1-6Alkyl groups may be substituted with one or more a. In one embodiment of the invention R¹Is ethyl and A is hydroxy.

[0116]In a more suitable embodiment of the invention, R¹Selected from the group consisting of hydrogen, methyl, ethyl, cyclopropyl, hydroxy, methoxy, cyano, fluoro, chloro, bromo, iodo, trifluoromethyl, difluoromethoxy, trifluoromethoxy, amino, nitro, dimethylamino, methylthioalkyl, vinyl, acetyl, methyl formate, methoxymethyl, ethanol and furyl.

[0117]In a more suitable embodiment of the invention P is selected from thienyl, pyridyl, thiazolyl, furyl, pyrrolyl or phenyl, wherein the phenyl ring is substituted in the 3-position or disubstituted in the 2-and 5-positions and R is¹Selected from hydrogen, hydroxy, halogen, nitro, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_1-6Alkyl radical, OC_1-6Alkyl radical, C_2-6Alkenyl radical, C_0-6Alkyl radical C_3-6Cycloalkyl radical, C_1-6Alkyl OR⁵，C_1-6Alkyl (CO) R⁵，C_0-6Alkyl group CO₂R⁵，C_0-6Alkylcyano radical, C_0-6Alkyl radical NR⁵R⁶，C_0-6Alkyl SR⁵And a 5-membered ring comprising one or more atoms independently selected from C and O.

[0118]In a more suitable embodiment of the invention P is phenyl substituted in position 3 or phenyl disubstituted in positions 2 and 5 and R¹Selected from hydrogen, hydroxy, halogen, nitro, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_1-6Alkyl radical, OC_1-6Alkyl radical, C_2-6Alkenyl radical, C_0-6Alkyl radical C_2-6Cycloalkyl radical, C_1-6Alkyl OR⁵，C_1-6Alkyl (CO) R⁵，C_0-6Alkyl group CO₂R⁵，C_0-6Alkylcyano radical, C_0-6Alkyl radical NR⁵R⁶，C_0-6Alkyl SR⁵And a 5-membered ring comprising one or more atoms independently selected from C and O.

[0119]According to another aspect of the invention, ring P is through M¹To the core ring, wherein M¹May be a bond directly connecting P to the core ring. M¹Or may be a linking C_1-3An alkyl group.

[0120]In a preferred embodiment of the invention M ¹Is a bond.

[0121]When M is¹Not a direct bond M¹When M is in contact with¹May be further substituted by 0, 1, 2 or 3 substituents R²Substituted, wherein the substituent R²Is designated by the term n. Substituent R²Can be selected from hydrogen, hydroxy, oxo, C_1-4Alkyl halo, halogen and C_1-4An alkyl group. In a preferred embodiment of the invention n is 0.

[0122]In another aspect of the invention there is provided a compound of formula I wherein X¹Selected from C, CO, N, O and S. In another aspect of the present invention, X²Selected from C, N, O and S. In another aspect of the invention, X³Selected from N, O and S, or when X is²Selected from N, O or X at S³Selected from N, O, S and C, and when X is³Is C or X³The substituent R on (A) is H.

[0123]X¹、X²And X³Further substituted with 0, 1 or 2 substituents R, wherein the number of substituents R is specified by the term t. The substituents R may be selected from: hydrogen, C_0-3Alkyl, halogen, C_0-3Alkyl OR⁵，C_0-3Alkyl radical NR⁵R⁶，C_0-3Alkyl (CO) OR⁵，C_0-3Alkyl radical NR⁵R⁶And C_0-3An alkylaryl group. In one embodiment of the invention R is selected from hydrogen, C_0-3Alkyl and halogen.

[0124]In a preferred embodiment of the invention X¹Is C, N or O, and R is selected from hydrogen, C_0-3Alkyl and halogen. In one embodiment, R is selected from hydrogen, chloro or methyl.

[0125]In a further preferred embodiment of the invention X¹Is N.

[0126]In one suitable embodiment X ²Selected from N, O and S, R is hydrogen. In another embodiment of the present invention X³Is N, O or S. In another preferred embodiment of the present invention, X¹Is O, X²And X³One is O and the other is N. In a further preferred embodiment of the present invention, X¹Is N, X²And X³One is O and the other is N. In yet another preferred embodiment of the present invention, X¹Is C or CR, X²And X³One is O and the other is N.

[0127]In another embodiment of the present invention, X²Is O, X³Is N, and in a further preferred embodiment X²Is N, X³Is O.

[0128]In a more preferred embodiment of the present invention X¹Is O, X²And X³Is N.

[0129]Another suitable embodiment of the invention comprises X¹、X²And X³To form oxadiazole, isoxazole, oxazole, chloro-isoxazole or methyl-isoxazole.

[0130]In a preferred embodiment of the present invention comprises X¹、X²And X³The ring of (a) forms an oxadiazole. In another preferred embodiment of the present invention comprises X¹、X²And X³The ring of (a) forms isoxazole.

[0131]Comprising X¹、X²And X³The ring of (2) is not further looped with other rings.

[0132]In a suitable embodiment of the invention M²Can be a core ring with variable X⁴A direct bond therebetween, or M²Selected from the group consisting of a bond, C_1-3Alkyl radical, C_2-3Alkynyl, C _0-4Alkyl (CO) C_0-4Alkyl radical, C_0-3Alkyl OC_0-3Alkyl radical, C_0-3Alkyl radical NR⁵C_1-3Alkyl radical, C_0-3Alkyl (CO) NR⁵，C_0-4Alkyl radical NR⁵，C_0-3Alkyl (SO) C_0-3Alkyl and C_0-3Alkyl (SO)₂)C_0-3An alkyl group.

[0133]In a preferred embodiment of the invention M²Is a bond or C_1-3An alkyl group. In a more preferred embodiment of the invention M²Is C_1-3Alkyl, preferably methyl or ethyl.

[0134]When M is²When not a direct bond, M²May be further substituted by 0, 1 or 2R³Is substituted by radicals in which the substituent R³Is designated by the term n. In one embodiment of the invention n is 1 or 2. In another embodiment of the invention n is 0.

[0135]In a suitable embodiment of the invention R³Selected from: hydroxy radical, C_0-6Alkyl cyano, oxo, ═ NR⁵，＝NOR⁵，C_1-4Alkyl halides, halogens, C_1-4Alkyl, O (CO) C_1-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, OC_1-4Alkyl radical, C_1-4Alkyl OR⁵And C_0-4Alkyl radical NR⁵R⁶。

[0136]In a preferred embodiment R³Selected from hydrogen and C_1-4Alkyl, preferably methyl or dimethyl.

[0137]In another preferred embodiment M²Selected from: bond, C_1-3Alkyl radical, C_2-3Alkynyl, C_0-4Alkyl (CO) C_0-4Alkyl radical, C_0-3Alkyl OC_0-3Alkyl radical, C_0-3Alkyl radical NR⁵C_1-3Alkyl radical, C_0-3Alkyl (CO) NR⁵，C_0-4Alkyl radical NR⁵，C_0-3Alkyl (SO) C_0-3Alkyl and C_0-3Alkyl (SO)₂)C_0-3Alkyl radical, R³Selected from hydrogen and C_1-4An alkyl group.

[0138]In a further preferred embodiment of the invention, M²Is a bond or C_1-3Alkyl radical, R³Is hydrogen, methyl or dimethyl.

[0139]In a more preferred embodiment M²May be selected from a bond, methyl and ethyl, R³Is hydrogen, methyl or dimethyl.

[0140]In a more preferred embodiment M²Is nitrogen. In a further more preferred embodiment M²Is oxygen.

[0141]According to another aspect X of the invention⁴Selected from: c_0-4Alkyl radical R⁵R⁶，C_3-7Cycloalkyl radical, C_1-4Alkyl (NR)⁵R⁶)，NR⁵，C_0-4Alkyl (NR)⁵R⁶)＝N，NR⁵C_0-4Alkyl (NR)⁵R⁶)＝N，NOC_0-4Alkyl radical, C_1-4Alkyl halo, O, SO₂And S, wherein M²And X⁴The bond in between is a single bond.

[0142]In a preferred embodiment of the invention, X⁴Is selected from C_0-4Alkyl radical R⁵R⁶，C_3-7Cycloalkyl radicals, NR⁵，O，SO，SO₂And S, R⁵And R⁶Independently selected from hydrogen and C_1-6An alkyl group.

[0143]In a further preferred embodiment of the present invention, X⁴Selected from: CH (CH)₂，CHCH₃，CH(CH₃)₂And NR₅. In a further preferred embodiment of the present invention, X⁴Is NR⁵，R⁵Selected from hydrogen and C_1-6An alkyl group. In a preferred embodiment of the invention R⁵Is methyl or hydrogen, R⁶Is hydrogen.

[0144]In a still further preferred embodiment of the present invention X⁴Is O. In another preferred embodiment of the present invention X⁴Is S.

[0145]It is to be understood that M is in any tautomeric form²And X⁴All of the bonds in between are single bonds.

[0146] Embodiments of the invention include those wherein Q is a 5 or 6 membered ring.

[0147]When Q is a 5-membered ring, Q is selected from: triazolyl, imidazolyl, oxadiazolyl, imidazolinonyl, oxazolonyl, thiazolonyl, tetrazolyl and thiadiazolyl, wherein any one substitutable nitrogen atom of the ring is substituted on the nitrogen atom by R⁴And (4) substitution.

[0148] In one embodiment the 5 membered ring Q is selected from triazolyl and thiadiazolyl. In another embodiment the 5 membered ring Q is selected from tetrazolyl and oxadiazolyl. In yet another embodiment 5-membered ring Q is imidazolyl.

[0149] When Q is a 6 membered ring, Q is selected from: benzimidazolyl, benzoxazolyl, tetrahydrotriazolopyridinyl, tetrahydrotriazolopyrimidinyl, pyridonyl, pyridazinyl, imidazopyridinyl, oxazolopyridyl, thiazolopyridyl, imidazopyridazinyl, oxazolopyridazinyl, thiazolopyridazinyl and purinyl.

[0150] In a preferred embodiment of the present invention, Q of the 6-membered ring is selected from the group consisting of pyridonyl, tetrahydrotriazolopyridinyl and tetrahydrotriazolopyrimidinyl. In another embodiment Q of the 6 membered ring is pyridazinyl. In yet another embodiment Q of the 6 membered ring is selected from the group consisting of benzimidazolyl, benzoxazolyl and imidazopyridinyl.

[0151]Q may be further substituted by 0, 12 or 3 substituents R ⁴Is substituted in which R⁴Is designated by the term m 2. In a preferred embodiment m2 is 1 or 2. When Q is a 5-membered ring, the substituent R⁴Selected from: c_0-6Alkyl cyano, ═ NC_1-4Alkyl, ═ NOR⁵，C_1-4Alkyl halides, halogens, C_1-6Alkyl radical, OC_1-4Alkyl radical, C_2-4Alkenyl radical, C_0-2Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl group, C_0-6Alkylheteroaryl, OC_0-6Alkylaryl, OC_0-6Alkylheteroaryl, NC_0-6Alkylaryl, NC_0-6Alkyl heteroaryl radical, C_0-6Alkyl Oaryl, C_0-6Alkyl O heteroaryl, C_0-6alkyl-N-aryl, C_0-6Alkyl N heteroaryl, OC_0-6Alkyl Oaryl, OC_0-6Alkyl O heteroaryl, OC_0-6Alkyl N aryl, OC_0-6Alkyl N heteroaryl, NC_0-6Alkyl Oaryl, NC_0-6Alkyl O heteroaryl, NC_0-6alkyl-N-aryl, NC_0-6Alkyl N heteroaryl, O (CO) C_1-4Alkyl radical, C_0-4Alkyl (CO) OC_1-4Alkyl radical, C_1-4Alkyl (S) C_0-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, C_1-4Alkyl OR⁵，C_0-4Alkyl radical N (C)_1-4Alkyl radical)₂And a 3-or 6-membered non-aromatic ring comprising one or more atoms independently selected from C, N, O and S, which ring may optionally be fused to a 5-membered ring comprising one or more atoms independently selected from C, N and O, wherein said ring and said fused ring may be substituted with one or two A' S.

[0152]In another embodiment of the invention R on the 5-membered ring Q⁴Selected from: c_1-4Alkyl halo, C_1-6Alkyl radical, C_2-4Alkenyl radical, C_0-2Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl group, C_0-6Alkylheteroaryl, OC_0-6Alkylaryl, OC_0-6Alkylheteroaryl, NC_0-6Alkylaryl, NC_0-6Alkyl heteroaryl radical, C_0-6Alkyl Oaryl, C_0-6Alkyl O heteroaryl, C_0-6alkyl-N-aryl, C_0-6Alkyl N heteroaryl, OC_0-6Alkyl Oaryl, OC_0-6Alkyl O heteroaryl, OC_0-6Alkyl N aryl, OC_0-6Alkyl N heteroaryl, NC_0-6Alkyl Oaryl, NC_0-6Alkyl O heteroaryl, NC_0-6alkyl-N-aryl, NC_0-6Alkyl N heteroaryl, C_0-4Alkyl (CO) OC_1-4Alkyl radical, C_1-4Alkyl (S) C_0-4Alkyl radical, C_1-4Alkyl OR⁵And a 3-or 6-membered non-aromatic ring comprising one or more atoms independently selected from C, N, O and S, which ring may optionally be fused to a 5-membered ring comprising one or more atoms independently selected from C, N and O, wherein said ring and said fused ring may be substituted with one or two A' S.

[0153]In one embodiment of the invention Q is selected from: triazolyl, imidazolyl, oxadiazolyl, imidazolinonyl, oxazolonyl, thiazolonyl, tetrazolyl and thiadiazolyl, wherein any substitutable nitrogen atom of the ring is substituted on the nitrogen atom by R⁴Substituted, R⁴Selected from: c _1-4Alkyl halo, C_1-6Alkyl radical, C_2-4Alkenyl radical, C_0-2Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl group, C_0-6Alkylheteroaryl, OC_0-6Alkylaryl, OC_0-6Alkylheteroaryl, NC_0-6Alkylaryl, NC_0-6Alkyl heteroaryl radical, C_0-6Alkyl Oaryl, C_0-6Alkyl O heteroaryl, C_0-6alkyl-N-aryl, C_0-6Alkyl N heteroaryl, OC_0-6Alkyl Oaryl, OC_0-6Alkyl O heteroaryl, OC_0-6Alkyl N aryl, OC_0-6Alkyl N heteroaryl, NC_0-6Alkyl Oaryl, NC_0-6Alkyl O heteroaryl, NC_0-6alkyl-N-aryl, NC_0-6Alkyl N heteroaryl, C_0-4Alkyl (CO) OC_1-4Alkyl radical, C_1-4Alkyl (S) C_0-4Alkyl radical, C_1-4Alkyl OR⁵To do so byAnd a 3-or 6-membered non-aromatic ring comprising one or more atoms independently selected from C, N, O and S, which ring may optionally be fused to a 5-membered ring comprising one or more atoms independently selected from C, N and O, wherein said ring and said fused ring may be substituted with one or two A' S.

[0154]In another embodiment of the invention, Q is selected from: triazolyl, imidazolyl, oxadiazolyl, tetrazolyl and thiadiazolyl, wherein any substitutable nitrogen atom of the ring is substituted on said nitrogen atom by R⁴Substituted, R⁴Selected from: c_1-4Alkyl halo, C_1-6Alkyl radical, C_2-4Alkenyl radical, C_0-2Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl group, C_0-6Alkylheteroaryl, OC _0-6Alkylaryl, OC_0-6Alkylheteroaryl, NC_0-6Alkylaryl, NC_0-6Alkyl heteroaryl radical, C_0-6Alkyl Oaryl, C_0-6Alkyl O heteroaryl, C_0-6alkyl-N-aryl, C_0-6Alkyl N heteroaryl, OC_0-6Alkyl Oaryl, OC_0-6Alkyl O heteroaryl, OC_0-6Alkyl N aryl, OC_0-6Alkyl N heteroaryl, NC_0-6Alkyl Oaryl, NC_0-6Alkyl O heteroaryl, NC_0-6alkyl-N-aryl, NC_0-6Alkyl N heteroaryl, C_0-4Alkyl (CO) OC_1-4Alkyl radical, C_1-4Alkyl (S) C_0-4Alkyl radical, C_1-4Alkyl OR⁵And a 3-or 6-membered non-aromatic ring comprising one or more atoms independently selected from C, N, O and S, which ring may optionally be fused to a 5-membered ring comprising one or more atoms independently selected from C, N and O, wherein said ring and said fused ring may be substituted with one or two A' S.

[0155]When Q is a 6-membered ring, the substituent R⁴Selected from: hydrogen, hydroxy, C_0-6Alkyl cyano, ═ NR⁵，＝NOR⁵，C_1-4Alkyl halides, halogens, C_1-6Alkyl radical, OC_1-4Alkyl radical, OC_0-6Alkylaryl, O (CO) C_1-4Alkyl radical, C_0-4Alkyl (S) C_0-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, C_1-4Alkyl OR⁵，C_0-4Alkyl radical NR⁵R⁶And a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S, which ring may optionally be fused to a 5-or 6-membered ring comprising one or more atoms independently selected from C, N and O, wherein said ring and said fused ring may be substituted with one or two A' S.

[0156]In one suitable embodiment of the invention R is on the 6-membered ring Q⁴Selected from hydrogen and C_1-6An alkyl group. In another embodiment of the invention, R⁴Is hydrogen, methyl, ethyl, propyl, butyl or hexyl.

[0157]In a preferred embodiment of the invention, Q is selected from: benzimidazolyl, benzoxazolyl, tetrahydrotriazolopyridyl, tetrahydrotriazolopyrimidinyl, pyridonyl, pyridazinyl, imidazopyridinyl, oxazolopyridyl, thiazolopyridyl, imidazopyridazinyl, oxazolopyridazinyl, thiazolopyridazinyl and purinyl, R⁴Is hydrogen or C_1-6An alkyl group.

[0158]In another preferred embodiment of the invention Q is selected from: benzimidazolyl, benzoxazolyl, tetrahydrotriazolopyridyl, tetrahydrotriazolopyrimidinyl, pyridonyl, pyridazinyl, imidazopyridinyl, R⁴Is hydrogen or C_1-6An alkyl group.

[0159]In a suitable embodiment of the invention R⁴Selected from: benzo [ b ]]Thienyl, benzodioxolyl, bromo, bromofuryl, butoxyphenyl, chloromethoxypyridyl, chlorophenyl, chlorophenylmethanol, chloropyridyl, chlorothiophene, cyanophenyl, cyclohexyl, cyclopentyl, dichlorophenyl, dichloropyridyl, difluorophenyl, dimethylthiazolyl, ethanol, ethoxymethyl, fluoromethylphenyl, fluorophenyl, methyl formate, furyl, hydrogen, hydroxyphenoxymethyl, hydroxyphenyl, imidazolyl, methoxyethyl, methoxymethyl A group selected from the group consisting of phenyl, methoxyphenoxymethyl, methoxyphenyl, methoxyphenylethyl, methoxypyridazinyl, methoxypyridyl, methoxypyrimidinyl, methoxythiophene, methylimidazolyl, methylpyridyl, methylthiomethyl, methylthiazole, methylthio, nitrofuranyl, nitrophenyl, phenyl, p-tolyloxymethyl, pyridazinyl, pyridyloxy, benzylmorpholinyl, pyridonyl, pyridyl, pyridylmethyl, pyrimidinyl, tert-butylphenyl, tetrahydrofuryl, thiazolyl, thiophene, tolyl, trifluoromethyl, methyl acetate, allyl, amino, benzyl, cyclopropylmethyl, ethyl, fluorobenzyl, fluoroethyl, furanmethyl, hydroxyethyl, isobutyl, methyl, methylbenzyl, methylbutyl, methylthiopropyl, n-butyl, n-hexyl, n-propyl, tetrahydrofuryl, thiophenylmethyl and trifluoroethyl.

[0160]The carbon and/or nitrogen atoms on ring Q may be replaced by one or more R⁴And (4) substitution. When the carbon atom on Q is substituted, R⁴Selected from benzo [ b]Thienyl, benzodioxolyl, bromo, bromofuryl, butoxyphenyl, chloromethoxypyridyl, chlorophenyl, chlorophenylmethanol, chloropyridyl, chlorothiophene, cyanophenyl, cyclohexyl, cyclopentyl, dichlorophenyl, dichloropyridyl, difluorophenyl, dimethylthiazolyl, ethanol, ethoxymethyl, fluoromethylphenyl, fluorophenyl, methyl formate, furyl, hydrogen, hydroxyphenoxymethyl, hydroxyphenyl, imidazolyl, methoxyethyl, methoxymethyl, methoxyphenoxymethyl, methoxyphenyl, methoxyphenylethyl, methoxypyridazinyl, methoxypyridyl, methylthiothiophene, methylimidazolyl, methylpyridyl, methylthiomethyl, methylthiazolyl, methylthiothiophene, nitrofuryl, nitrophenyl, phenyl, p-tolyloxymethyl, pyridazinyl, pyridyloxy, benzylmorpholinyl, pyridinonyl, pyridyl, pyridylmethyl, pyrimidinyl, tert-butylphenyl, tetrahydrofuryl, thiazolyl, thiophene, tolyl and trifluoromethyl.

[0161]When the nitrogen atom of Q is substituted, R⁴Selected from methyl acetate, allyl, amino, benzyl, cyclopropyl, cyclopropylmethyl, ethylA fluorine-containing group, a fluorine-containing group.

[0162]When R is⁴When it is a ring, R⁴May be substituted by one or more substituents A, wherein A is selected from hydrogen, hydroxy, halogen, nitro, oxo, C_0-6Alkylcyano radical, C_0-4Alkyl radical C_3-6Cycloalkyl radical, C_1-6Alkyl radical, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_2-6Alkenyl radical, C_0-3Alkylaryl group, C_0-6Alkyl OR⁵，OC_2-6Alkyl OR⁵，C_1-6Alkyl SR⁵，OC_2-6Alkyl SR⁵，(CO)R⁵，O(CO)R⁵，OC_2-6Alkylcyano, OC_1-6Alkyl group CO₂R⁵，O(CO)OR⁵，OC_1-6Alkyl (CO) R⁵，C_1-6Alkyl (CO) R⁵，NR⁵OR⁶，OC_2-6Alkyl radical NR⁵R⁶，C_0-6Alkyl (CO) NR⁵R⁶，OC_1-6Alkyl (CO) NR⁵R⁶，OC_2-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)NR⁵R⁶，O(CO)NR⁵R⁶，C_0-6Alkyl (SO)₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)NR⁵R⁶，C_0-6Alkyl radical NR⁵(SO₂)R⁶，OC_2-6Alkyl radical NR⁵(SO₂)R⁶，SO₃R⁵，C_1-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)R⁵，C_0-6Alkyl (SO)₂)R⁵，C_0-6Alkyl (SO) R⁵，OC_2-6Alkyl (SO) R⁵And comprises one or more independent optionsA 5-membered ring of atoms from C, N, O and S.

[0163]In a preferred embodiment A is selected from hydroxy, halogen, nitro, oxo, C_0-6Alkylcyano radical, C_1-6Alkyl radical, C_2-6Alkenyl radical, C_0-3Alkylaryl group, C _0-6Alkyl OR⁵And a 5-membered ring comprising one or more atoms independently selected from C and O.

[0164] Particular embodiments of the present invention include that,

2- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1H-benzimidazole

5- (3-methoxy-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- [5- (1-methyl-5-thiophen-2-yl-1H-imidazol-2-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-3-yl ] -benzonitrile,

3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-phenyl- [1, 2, 4] oxadiazole

2- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -5-methyl-1H-benzimidazole,

3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-trifluoromethyl-phenyl) - [1, 2, 4] oxadiazole,

3- (3-methoxy-phenyl) -5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (4-methyl-5-thiophen-2-yl-H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-phenyl [1, 2, 4] oxadiazole,

5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-m-tolyl- [1, 2, 4] oxadiazole,

3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -benzonitrile,

3- [ 4-methyl-5- (2-methyl-thiazol-4-yl) -4H- [1, 2, 4] tri-3-ylsulfanylmethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole,

3- [5- (-methyl-thiazol-4-yl) - [1, 3, 4] oxadiazol-2-ylsulfanylmethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole,

3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiophen-2-yl [1, 2, 4] oxadiazole,

3- [5- (2, 4-dimethyl-thiazol-5-yl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole,

3- [ 4-methyl-5- (5-nitro-furan-2-yl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole,

4- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

3- [5- (4-tert-butyl-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] -5-m-tolyl- [1, 2, 4] -oxadiazole,

2-chloro-5- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

2- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -benzoxazole,

3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiophen-3-yl- [1, 2, 4] oxadiazole,

3- (5-furan-2-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

5- (3-fluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

2- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -pyridine,

2- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1H-imidazo [4, 5-b ] pyridine,

5- (3-fluoro-5-methyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3-methyl-5- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

3- (4-methyl-5-phenyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

2- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

4-benzyl-2- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -morpholine,

4- [ 4-methyl-5- (5-thiophen-3-yl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiazol-4-yl [1, 2, 4] oxadiazole,

3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-nitro-phenyl) - [1, 2, 4] oxadiazole,

2-methyl-4- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

3- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

3- (4-methyl-5-thiazol-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

5- (3-iodo-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-ethyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

2- [5- (2-methyl-py-rin-4-yl) - [1, 2, 4] oxadiazol 3-ylmethylthio ] -1H-benzimidazole,

2- [5- (3-iodo-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1H-benzimidazole,

3- (4-methyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

2, 6-dichloro-4- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

3- (4-methyl-5-p-tolyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

dimethyl- {3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] phenyl } -amine,

5- (3-chloro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-trifluoromethoxy-phenyl) - [1, 2, 4] oxadiazole,

3- (5-cyclohexyl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl [1, 2, 4] oxadiazole,

3- (5-tert-butyl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

5- (3-bromo-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

2- [5- (3-yl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1H-benzimidazole,

5- (3-methoxymethyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

2- [5- (3-methoxymethyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1H-benzimidazole,

4- [5 (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-3-yl ] -pyridine,

2- {1- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -1-methyl-1H-imidazo [4, 5-b ] pyridine,

2- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1-methyl-1H-imidazo [4, 5-b ],

3- [ 1-methyl-1- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole,

3- [1- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole,

3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole-3-sulfonylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole-3-sulfinylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole, or

5- (3-furan-3-yl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole, or a salt thereof.

[0165] A further specific embodiment of the present invention includes,

4- (4-cyclopropyl-5- {1- [5- (2, 5-difluoro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- { 4-methyl-5- [1- (5-m-tolyl- [1, 2, 4] oxadiazol-3-yl) -ethylthio ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-o-tolyl- [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (4-cyclopropyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

2- {3- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -5-thiophen-2-yl- [1, 2, 4] triazol-4-yl } -ethanol,

4- { 4-Ethyl-5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyrimidine,

3- (4-Ethyl-5-furan-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazole,

{3- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -5-thiophen-2-yl- [1, 2, 4] triazol-4-yl } -acetic acid methyl ester,

5- (2-fluoro-5-methyl-phenyl) -3- [ 5-furan-2-yl-4- (2-methoxy-ethyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

3- (4-cyclopropyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazole,

3- (5-chloro-2-fluoro-phenyl) -5- (4-cyclopropylmethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- {5- [3- (5-fluoro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-5-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyrimidine,

3- (5-cyclopentyl-4-ethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

3- (3-chloro-phenyl) -5- { 4-ethyl-5- [2- (4-methoxy-phenyl) -ethyl ] -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl } - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (4-ethyl-5-p-tolyloxymethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [4- (2-methoxy-ethyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

3- (5-chloro-2-fluoro-phenyl) -5- (4-ethyl-5-methoxymethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (5-chloro-2-fluoro-phenyl) -3- (4-ethyl-5-methoxymethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (4-ethyl-5-methoxymethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (3-chloro-phenyl) -5- (4-ethyl-5-methoxymethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- (5- {1- [3- (3-chloro-phenyl) -isoxazol-5-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

3- (4-allyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole,

3- (4-allyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiophen-3-yl [1, 2, 4] oxadiazole,

5- (4-allyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-furan-2-yl [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (4-methoxy-phenoxymethyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

3- (3-chloro-phenyl) -5- [ 4-ethyl-5- (4-methoxy-phenoxymethyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

{5- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -methanol,

3- (3-chloro-phenyl) -5- [ 4-ethyl-5- (2-methoxy-ethyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

3- (3-chloro-phenyl) -5- (4-ethyl-5-methylthiomethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (3-chloro-phenyl) -5- (5-ethoxymethyl-4-ethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

5- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazole-3-carboxylic acid methyl ester,

2- (5-chloro-2-fluoro-phenyl) -5- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazole,

2- (3-chloro-phenyl) -5- (4-cyclopropyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazole,

5- (3-chloro-phenyl) -3- {1- [ 4-ethyl-5- (tetrahydro-furan-2-yl) -4H- [1, 2, 4] triazol-3-ylsulfanyl ] -ethyl } - [1, 2, 4] oxadiazole,

4- (5- {1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylthio } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -pyridazine,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-ylmethyl) -pyridine,

5- (5- {1- [5- (3-chlorobenzene) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -pyridin-2-ol,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -phenol,

5- (3-chloro-phenyl) -3- [5- (4-methoxy-phenoxymethyl) -4- (tetrahydro-furan-2-ylmethyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [ 4-cyclopropyl-5- (4-methoxy-phenoxymethyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (5-chloro-2-fluoro-phenyl) -3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (4-ethyl-5-methoxymethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

3- [ 4-ethyl-5- (tetrahydro-furan-2-yl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole,

2- (3-chloro-phenyl) -5- {1- [ 4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4] triazol-3-ylsulfanyl ] -ethyl } - [1, 3, 4] oxadiazole,

4- {5- [3- (2, 5-difluoro-phenyl) - [1, 2, 4] oxadiazol-5-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyrimidine,

4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyrimidine,

3- (3-chloro-phenyl) -5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-methylsulfanyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

2- [5- (3-methylsulfanyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1H-benzimidazole,

5- (2, 5-dimethyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (2-fluoro-5-methyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-cyclopropyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- {5- [2- (3-chlorophenyl) -oxazol-4-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- [ 4-methyl-5- (5-thiophen-2-yl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

4- { 4-methyl-5- [5- (3-methylsulfanyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

2-methyl-4- [3- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

1- {3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -phenyl } -ethanone (ethanone),

4- {5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

2-methyl-4- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

3- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-methyl 5-thiophen-2-yl-4H- [1, 2, 4] triazole,

4- {5- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- (4-butyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [4- (3-methoxy-propyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

3- (4-benzyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole,

5 (3-chloro-phenyl) -3- (4-furan-2-ylmethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (3-chloro-phenyl) -3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- {5- [5- (-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -2-methyl-pyridine,

5- (5-chloro-2-fluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- {5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (3-chloro-phenyl) -3- (5-thiophen-2-yl-4-thiophen-2-ylmethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl- [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- {5- [3- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-5-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- {5- [3- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-5-ylmethioni-yl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- {5- [5- (5-bromo-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethioni-yl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- {5- [5- (5-bromo-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (5-bromo-2-fluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-phenyl- [1, 2, 4] oxadiazole,

3- {5- [5- (3-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- {5- [5- (3-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethioni-yl ] -4-methyl-4-H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (3-fluoro-phenyl) -3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- [ 4-methyl-5- (5-thiophen-3-yl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiophen-3-yl- [1, 2, 4] oxadiazole,

2-chloro-4- [3- (4-methyl-5-pyridin-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

2-chloro-4- [3- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

2-chloro-4- [3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

4- [ 4-methyl-5- (5-phenyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-phenyl- [1, 2, 4] oxadiazole,

5- (5-bromo-2-fluoro-phenyl) -3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole,

2-chloro-4- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

4- {5- [3- (3-fluoro-phenyl) - [1, 2, 4] oxadiazol-5-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- (3-fluoro-phenyl) -5- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazole,

4- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-furan-2-ylmethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (3-chloro-phenyl) -3- (4-ethyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethioni-yl ] -4-furan-2-ylmethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- (4-furan-2-ylmethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

5- (5-fluoro-2-methyl-phenyl) -3- (4-furan-2-ylmethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (4-furan-2-ylmethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- [3- (4-methyl-5-pyridin-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -benzonitrile,

3- [3- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -benzonitrile,

3- [3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -benzonitrile,

5- (5-chloro-2-fluoro-phenyl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

2-chloro-4- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiophen-3-yl- [1, 2, 4] oxadiazole,

3- (4-ethyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

4- [ 4-ethyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

3- [ 4-ethyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

3- (4-ethyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazole,

4- { 4-Ethyl-5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- { 4-Ethyl-5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -5-pyridin-4-yl- [1, 2, 4] triazol-4-ylamine,

4- {5- [5- (5-bromo-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-thiophen-2-yl- [1, 2, 4] oxadiazole,

3- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -benzonitrile,

3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-phenyl- [1, 2, 4] oxadiazole,

4- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -2-methoxy-pyridine,

3- (3-chloro-phenyl) -5- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- {5- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

2-methyl-4- [3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

4- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -2-methyl-pyridine,

5- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-thiophen-2-yl- [1, 2, 4] oxadiazole,

4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- [3- (4-ethyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -2-methyl-pyridine,

3- {5- [5- (3-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethioni-yl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -benzonitrile,

5- (3-chloro-phenyl) -3- [5- (3-chloro-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [5- (4-chloro-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

4- {5- [5- (2, 5-dichloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-ethyl 4H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (2, 5-dichloro-phenyl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (2, 5-difluoro-phenyl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- {5- [5- (2, 5-difluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (2, 5-dichloro-phenyl) -3- (4-ethyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (2, 5-difluoro-phenyl) -3- (4-ethyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-propyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- {5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-propyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiophen-2-yl- [1, 2, 4] oxadiazole,

3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiophen-2-yl- [1, 2, 4] oxadiazole,

4- [ 4-methyl-5- (3-thiophen-3-yl- [1, 2, 4] oxadiazol-5-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

5- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-thiophen-3-yl [1, 2, 4] oxadiazole,

5- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-thiophen-3-yl [1, 2, 4] oxadiazole,

5- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -thiophene-3-carbonitrile,

5- (3-chloro-phenyl) -3- [5- (2-fluoro-phenyl) 4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [5- (3-fluoro-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [5- (4-fluoro-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

3- (5-benzo [ b ] thiophen-2-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [5- (3-methoxy-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

3- (4-Ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazole,

3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole,

3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazole,

3- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -5-pyridin-4-yl [1, 2, 4] triazol-4-ylamine,

3- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -5-thiophen-2-yl- [1, 2, 4] triazol-4-ylamine,

3-pyridin-4-yl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylthio) - [1, 2, 4] triazol-4-ylamine,

3-thiophen-2-yl-5- (5-m-tolyl [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) - [1, 2, 4] triazol-4-ylamine,

3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiophen-3-yl- [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- [3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -2-methyl-pyridine,

5- (2, 5-difluoro-phenyl) -3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- [ 4-ethyl-5- (5-thiophen-3-ylisoxazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

4-ethyl-3-furan-2-yl-5- (5-thiophen-3-yl-isoxazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazole,

5- (3-chloro-phenyl) -3- [5- (3, 5-dichloro-phenyl) -4-ethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (4-ethyl-5-p-tolyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (4-ethyl-5-m-tolyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (3-nitro-phenyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

4- {5- [3- (3-chloro-phenyl) -isoxazol-5-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (3-chloro-phenyl) -3- [5- (2, 5-difluoro-phenyl) -4-ethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [5- (3-chloro-phenyl) 4-ethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [5- (4-chloro-phenyl) -4-ethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

4- {5- [5- (3-chloro-phenyl) -oxazol-2-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- [5- (3-chloro-phenyl) -oxazol-2-ylmethylsulfanyl ] -4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole,

3- [5- (3-chloro-phenyl) -oxazol-2-ylmethylsulfanyl ] -4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazole,

5- (2-chloro-5-methyl-phenyl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- {5- [3- (3-chloro-phenyl) -isoxazol-5-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- [3- (3-chloro-phenyl) -isoxazol-5-ylmethylsulfanyl ] -4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole,

3- [3- (3-chloro-phenyl) -isoxazol-5-ylmethylsulfanyl ] -4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazole,

4- {5- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (2, 5-dichloro-thiophen-3-yl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- {5- [5- (2, 5-dichloro-thiophen-3-yl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- { 4-Ethyl-5- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

4-ethyl-3- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-ylmethylsulfanyl ] -5-thiophen-2-yl-4H- [1, 2, 4] triazole,

4-ethyl-3- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-ylmethylsulfanyl ] -5-furan-2-yl-4H- [1, 2, 4] triazole,

5- (3-chloro-phenyl) -3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (3-chloro-phenyl) -5- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiophen-3-yl- [1, 2, 4] oxadiazole,

5- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-thiophen-3-yl- [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (3-fluoro-phenyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [ 4-ethyl-5 (4-fluoro-phenyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiophen-2-yl- [1, 2, 4] oxadiazole,

3- {3- [5- (-chloro-thiophen-2-yl) -4-ethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazol-5-yl } -benzonitrile,

4- {5- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

2- (3-chloro-phenyl) -5- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [5- (2-fluoro-5-methyl-phenyl) -4-furan-2-ylmethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

4- [3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -2-methyl-pyridine,

3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazole,

5- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3- (3-methoxy-phenyl) - [1, 2, 4] oxadiazole,

5- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-thiophen-2-yl- [1, 2, 4] oxadiazole,

5- (5-chloro-2-fluoro-phenyl) -3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- [3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -benzonitrile,

3- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-ethyl 5-trifluoromethyl-4H- [1, 2, 4] triazole,

3- [5- (3-chloro-phenyl) -oxazol-2-ylmethylsulfanyl ] -4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazole,

4-ethyl-3 (5-thiophen-3-yl-isoxazol-3-ylmethylsulfanyl) -5-trifluoromethyl-4H- [1, 2, 4] triazole,

4- {3- [5- (3-fluoro-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazol-5-yl } -2-methyl-pyridine,

4- {3- [5- (3-chlorophenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazol-5-yl } -2-methyl-pyridine,

4- {3- [5- (4-chloro-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazol-5-yl } -2-methyl-pyridine,

4- {3- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazol-5-yl } -2-methyl-pyridine,

4- [3- (4-ethyl-5-p-tolyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -2-methyl-pyridine,

3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-fluoro-phenyl) - [1, 2, 4] oxadiazole,

4- { 4-Ethyl-5- [5- (3-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (3- (chloro-phenyl) -3- [5- (3, 5-difluoro-phenyl) -4-ethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [5- (2, 6-difluoro-phenyl) -4-ethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

2- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -4-methyl-phenol,

3- {1- [5- (3-chloro-phenyl) -isoxazol-3-yl ] -ethylsulfanyl } 4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazole,

4- (5- {1- [5- (3-chloro-phenyl) -isoxazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

3- [5- (4-butoxy-phenyl) -4-ethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] -5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole,

3- (5-benzo [1, 3] dioxol-5-yl-4-ethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole,

3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (2-methyl-thiazol-4-yl) - [1, 2, 4] oxadiazole,

3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (4-fluoro-phenyl) - [1, 2, 4] oxadiazole,

4-ethyl-3- {1- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl ] -ethylsulfanyl } -5-furan-2-yl-4H- [1, 2, 4] triazole,

4- (4-ethyl-5- {1- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl ] -ethylsulfanyl } -4H- [1, 2, 4] triazol-3-yl) -pyridine,

5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (3-methyl-3H-imidazol-4-yl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (1-methyl-1H-imidazol-2-yl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (1-methyl-1H-imidazol-4-yl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

4- {5- [5- (3-chloro-phenyl) -4-methyl-isoxazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- [5- (3-chloro-phenyl) -4-methyl-isoxazol-3-ylmethylsulfanyl ] -4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazole,

3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (4-methyl-thiophen-2-yl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (3-methyl-thiophen-2-yl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chlorophenyl) -3- [ 4-ethyl-5- (5-methyl-thiophen-2-yl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

4- {5- [ 4-chloro-5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- [ 4-chloro-5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazole,

2-chloro-4- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -6-methyl-pyridine,

3- [5- (5-bromo-furan-2-yl) -4-ethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] -5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole,

2-chloro-4- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

2-chloro-4- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -6-methoxy-pyridine,

2- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -4-methyl-benzonitrile,

5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (3-methoxy-thiophen-2-yl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

3- [5- (5-chloro-thiophen-3-yl) -isoxazol-3-ylmethylsulfanyl ] -4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazole,

3- [3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -5-fluoro-benzonitrile,

4-ethyl-3- (5-phenyl-isoxazol-3-ylmethylsulfanyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazole,

4-methyl-3- (5-phenyl-isoxazol-3-ylmethylsulfanyl) -5-thiophen-3-yl-4H- [1, 2, 4] triazole,

4-ethyl-3-furan-2-yl-5- (5-phenyl-isoxazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazole,

4- [ 4-ethyl-5- (5-phenyl-isoxazol-3-ylmethoxy) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

4- [ 4-methyl-5- (5-phenyl-isoxazol-3-ylmethoxy) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

2- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 3, 4] oxadiazole,

4- [ 4-methyl-5- (5-m-tolyl- [1, 3, 4] oxadiazol-2-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

4- [ 4-ethyl-5- (5-m-tolyl- [1, 3, 4] oxadiazol-2-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

4- {5- [5- (5-chloro-thiophen-3-yl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- [3- (4-ethyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -4-fluoro-benzonitrile,

3- [3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -4-fluoro-benzonitrile,

3- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -4-fluoro-benzonitrile,

3- [3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -benzonitrile,

3- [5- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-3-yl ] -benzonitrile,

3- [3- (4-methyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -benzonitrile,

5- (5-chloro-2-fluoro-phenyl) -3- (4-methyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

2-chloro-4- [3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

2-chloro-4- [3- (5-furan-2-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

2- (3-chloro-phenyl) -5- [ 4-methyl-5- (2-methyl-thiazol-4-yl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 3, 4] oxadiazole,

2- (3-chloro-phenyl) -5- (4-methyl-5-thiazol-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazole,

2- (3-chloro-phenyl) -5- (5-furan-2-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazole,

2- (3-chloro-phenyl) -5- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazole,

4- { 4-Ethyl-5- [5- (4-methyl-thiophen-2-yl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (4-methyl-thiophen-2-yl) - [1, 2, 4] oxadiazole,

3- (3-chloro-phenyl) -5- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- {5- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- { 4-Ethyl-5- [5- (3-nitro-phenyl) - [1, 3, 4] oxadiazol-2-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

2- (4-Ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-nitro-phenyl) - [1, 3, 4] oxadiazole,

4- {5- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

3- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4] triazole,

5- (3-chloro-phenyl) -3- [1- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [1- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] - [1, 2, 4] oxadiazole,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

3- [5- (4-ethyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazol-2-yl ] -benzonitrile,

3- [5- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazol-2-yl ] -benzonitrile,

3- [5- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazol-2-yl ] -benzonitrile,

3- [5- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazol-2-yl ] -benzonitrile,

4- {5- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- {5- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-ylmethylsulfanyl ] -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4] oxadiazol-2-ylmethylsulfanyl ] -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

2- (5-chloro-2-fluoro-phenyl) -5- [ 4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 3, 4] oxadiazole,

4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4] oxadiazol-2-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4] oxadiazol-2-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

2- (3-chloro-phenyl) -5- [ 4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 3, 4] oxadiazole,

2- (3-chloro-phenyl) -5- [1- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] - [1, 3, 4] oxadiazole,

5- (5-chloro-2-fluoro-phenyl) -3- [1- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] - [1, 2, 4] oxadiazole,

4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

2-chloro-4- [3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

4- {5- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] oxadiazol-2-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- { 4-Ethyl-5- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] oxadiazol-2-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- { 4-cyclopropyl-5- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] oxadiazol-2-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

2- (4-Ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] oxadiazole,

2- [ 4-Ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] -5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] oxadiazole,

4- {5- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- {5- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- {5- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl ] -ethylsulfanyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

3- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-ylmethylsulfanyl ] -4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazole,

3- {1- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl ] -ethylsulfanyl } -4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazole,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

5- (5-chloro-2-fluoro-phenyl) -3- (5-furan-2-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (5-chloro-2-fluoro-phenyl) -3- (5-furan-3-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4-chloro-2- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -phenol,

2-chloro-4- [5- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazol-2-yl ] -pyridine,

2-chloro-4- [5- (4-ethyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazol-2-yl ] -pyridine,

2-chloro-4- [5- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazol-2-yl ] -pyridine,

2-chloro-4- [5- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazol-2-yl ] -pyridine,

2-chloro 4- {5- [ 4-ethyl-5- (4-methoxy-phenyl) 4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 3, 4] oxadiazol-2-yl } -pyridine,

2- (3-chlorophenyl) -5- {1- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanyl ] -ethyl } - [1, 3, 4] oxadiazole,

4- (5- {1- [5 (5-chloro-2-fluoro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

5- (5-bromo-2-fluoro-phenyl) -3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

2- (3-chloro-phenyl) -5- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 3, 4] oxadiazole,

4- {5- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-ylmethioni-yl ] -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- (5- {1- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (4-ethyl-5- {1- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (4-cyclopropyl-5- {1- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (4-cyclopropylmethyl-5- {1- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4H- [1, 2, 4] triazol-3-yl) -pyridine,

2- (2-fluoro-5-methyl-phenyl) -5- {1- [ 4-methyl-5- (2-methyl-thiazol-4-yl) -4H- [1, 2, 4] triazol-3-ylsulfanyl ] -ethyl } - [1, 3, 4] oxadiazole,

4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

2- (5-chloro-2-fluoro-phenyl) -5- [1- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] - [1, 3, 4] oxadiazole,

2- (-chloro-2-fluoro-phenyl) -5- {1- [ 4-methyl-5- (2-methyl-thiazol-4-yl) -4H- [1, 2, 4] triazol-3-ylsulfanyl ] -ethyl } - [1, 3, 4] oxadiazole,

4- (4-cyclopropylmethyl-5- {1- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl ] -ethylsulfanyl } -4H- [1, 2, 4] triazol-3-yl-pyridine,

4- (5- {1- [5- (3-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylthio } 4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (4-cyclopropyl-5- {1- [5- (3-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanyl ] -ethyl } - [1, 3, 4] oxadiazol-2-yl) -2-methyl-pyridine,

4- (5- {1- [ 4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4] triazol-3-ylsulfanyl ] -ethyl } - [1, 3, 4] oxadiazol-2-yl) -2-methyl-pyridine,

4- {5- [1- (4-ethyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] - [1, 3, 4] oxadiazol-2-yl } -2-methyl-pyridine,

4- {5- [1- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] - [1, 3, 4] oxadiazol-2-yl } -2-methyl-pyridine,

4- {5- [1- (5-furan-2-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] - [1, 3, 4] oxadiazol-2-yl } -2-methyl-pyridine,

2- (3-chloro-phenyl) -5- {1- [ 4-methyl-5- (2-methyl-thiazol-4-yl) -4H- [1, 2, 4] triazol-3-ylsulfanyl ] -ethyl } - [1, 3, 4] oxadiazole,

3- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -2-methyl-pyridine,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

5- (3-chloro-phenyl) -3- {1- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanyl ] -ethyl } - [1, 2, 4] oxadiazole,

4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

5- (5-chloro-2-fluoro-phenyl) -3- {1- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanyl ] -ethyl } - [1, 2, 4] oxadiazole,

4- [5- (4-ethyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazol-2-yl ] -2-methyl-pyridine,

4- [5- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazol-2-yl ] -2-methyl-pyridine,

4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- [5- (5-furan-2-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 3, 4] oxadiazol-2-yl ] -2-methyl-pyridine,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylsulfanyl } -4-cyclopropylmethyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [5- (4-fluoro-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanyl ] -ethyl } - [1, 3, 4] oxadiazol-2-yl) -2-methyl-pyridine,

4- (5- {1- [5- (3-fluoro-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanyl ] -ethyl } - [1, 3, 4] oxadiazol-2-yl) -2-methyl-pyridine,

3- [3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -4-fluoro-benzonitrile,

4-chloro-2- [3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -phenol,

4- { 4-cyclopropyl-5- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- { 4-cyclopropyl-5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- { 4-cyclopropyl-5- [5- (3-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- [ 4-cyclopropyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine,

3- [3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -benzonitrile,

4- { 4-cyclopropyl-5- [5- (2, 5-difluoro-phenyl) - [1, 2, 4] oxadiazol 3-ylmethylsulfanyl ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- { 4-cyclopropyl-5- [1- (5-m-tolyl- [1, 2, 4] oxadiazol-3-yl) -ethylthio ] -4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- (4-cyclopropyl-5- {1- [5- (3-methoxyphenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- {5- [5- (2-chloro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

2- [3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -4-methyl-phenol,

4- (5- {1- [5- (2-chloro-5-methylphenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

{3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -phenyl } -methanol,

3- [5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-3-yl ] -phenol,

5- (3-chloro-phenyl) -3- [4- (tetrahydro-furan-2-ylmethyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

(2-chloro-phenyl) - {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-isobutyl-4H- [1, 2, 4] triazol-3-yl } -methanol,

5- (2-fluoro-5-methylphenyl) -3- [ 5-thiophen-2-yl-4- (2, 2, 2-trifluoro-ethyl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

3- (2, 5-difluoro-phenyl) -5- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5-furan-3-yl-3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (3-chloro-phenyl) -5- (5-furan-2-yl-4-methyl-4H [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (3-chloro-phenyl) -5- (5-furan-3-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (5-furan-2-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (5-furan-3-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyrimidine,

4- {5- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-ylmethioni-yl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyrimidine,

3- (5-chloro-2-fluoro-phenyl) -5- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (5-chloro-2-fluoro-phenyl) -5- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (5-chloro-thiophen-2-yl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (5-chloro-thiophen-2-yl) -3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (5-chloro-thiophen-3-yl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-ylmethoxy } -phenol,

4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4] oxadiazol-2-ylmethylsulfanyl ] -4-ethyl-4H- [1, 2, 4] triazol-3-ylmethoxy } -phenol,

3- (2, 5-difluoro-phenyl) -5- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (2, 5-difluoro-phenyl) -5- (5-furan-2-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

4- (5- {1- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl } -pyrimidine,

2- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -5-methoxy-pyrimidine,

2- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -pyrimidine,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -2-methoxy-pyridine,

5- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -2-methoxypyridine,

2- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -5-methoxy-pyridine,

3- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -6-methoxy-pyridazine,

3- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- {5- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

5- (3-chloro-phenyl) -3- (5-furan-2-yl-4-isobutyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [4- (3-methylsulfanyl-propyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (4-hexyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (4-cyclopropylmethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [4- (3-fluoro-benzyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [4- (3-methyl-benzyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [4- (2-methyl-butyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [4- (3-methylbutyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- [4- (2-fluoro-benzyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-yloxymethyl) - [1, 2, 4] oxadiazole,

4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethoxy ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethoxy } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [3- (3-chloro-phenyl) -isoxazol-5-yl ] -ethoxy } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

5- (2-methoxy-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5-furan-2-yl-3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -benzoic acid methyl ester,

5- (2-fluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (2, 5-difluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-ethenyl-phenyl) - [1, 2, 4] oxadiazole,

5- (3-difluoromethoxy-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (4-methoxy-thiophen-3-yl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (2-chloro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (4-fluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- (3-chloro-phenyl) -5- [1- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] - [1, 2, 4] oxadiazole,

- (5- {1- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

3- (3-chloro-phenyl) -5- [2- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-yl) -ethyl ] - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (5-furan-2-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylmethyl) - [1, 2, 4] oxadiazole,

2- (3-chloro-phenyl) -5- [2- (5-furan-2-yl-4-methyl-4H- [1, 2, 4] triazol-3-yl) -ethyl ] - [1, 3, 4] oxadiazole,

2- (3-chloro-phenyl) -5- [2- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-yl) -ethyl ] - [1, 3, 4] oxadiazole,

2- (3-chloro-phenyl) -5- [2- (4-cyclopropyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-yl) -ethyl ] - [1, 3, 4] oxadiazole,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -ethyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -ethyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -ethyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -propyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -2-methyl-propyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {2- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -propyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

8- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyridine,

8- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -3-thiophen-2-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyridine,

8- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyridine,

5- (5-bromo-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3- (3-chloro-phenyl) - [1, 2, 4] oxadiazole,

3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -aniline,

5- (3-chloro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole-3-sulfonylmethyl) - [1, 2, 4] oxadiazole,

5- (3-chloro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole-3-sulfinylmethyl) - [1, 2, 4] oxadiazole,

2-methyl-6- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine,

4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -pyridin-2-ol,

4- (5- {2- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -propyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

[5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -methyl- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -amine,

8- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -3-pyridin-4-yl 5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrimidine,

8- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -3-pyridin-4-yl 5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrimidine,

8- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-ylmethyl ] -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrimidine,

8- {1- [5- (3-fluoro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethyl } -3-pyridin-4-yl 5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrimidine,

8- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -3-furan-2-yl 5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrimidine,

8- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethyl } -3-pyridin-4-yl 5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrimidine,

3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (1H-pyrrol-3-yl) - [1, 2, 4] oxadiazole,

4- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine 1-oxide,

5- (3-chlorophenyl) -3- (2-furan-2-yl 3-methyl-3H-imidazol-4-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

5- (5-chloro-2-fluoro-phenyl) -3- [4- (2-fluoro-ethyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole,

5- (5-chloro-thiophen-3-yl) -3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole,

3- [3- (4-Ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -4-hydroxy-benzonitrile,

3- (3-chloro-phenyl) -5- [2- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-yl) -ethyl ] - [1, 2, 4] oxadiazole,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -propyl } - [1, 3, 4] oxadiazol-2-yl) -pyridine,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -1-methyl-ethyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -cyclopropyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine, or

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -1, 1-dimethyl-ethyl } - [1, 3, 4] oxadiazol-2-yl) -pyridine,

3- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethoxy } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [5- (2-chloro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [5- (2, 5-difluoro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {1- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (4-cyclopropyl-5- {1- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4H- [1, 2, 4] triazol-3-yl) -pyridine,

3- {3- [1- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl [1, 2, 4] oxadiazol-5-yl } -benzonitrile,

3- {3- [1- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] - [1, 2, 4] oxadiazol-5-yl } -benzonitrile,

3- {1- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethylthio } -5-pyridin-4-yl- [1, 2, 4] triazol-4-ylamine,

cis-4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -cyclopropyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -2-methylpropyl } - [1, 3, 4] oxadiazol-2-yl) -pyridine,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -1-methyl-ethyl } - [1, 3, 4] oxadiazol-2-yl) -pyridine,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -cyclopropyl } - [1, 3, 4] oxadiazol-2-yl) -pyridine,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -cyclopropyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {2- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -propyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -propyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

(S) - [1- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -2- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -ethyl ] -carbamic acid tert-butyl ester,

(S) -1- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -2- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -ethylamine,

(S) - [1- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -2- (4-cyclopropyl-5-pyridin-4-yl 4H- [1, 2, 4] triazol-3-yl) -ethyl ] -dimethylamine,

and salts thereof.

[0166] Other preferred embodiments of the present invention include:

4- (5- {2- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] propyl } -4-cyclopropyl-4H-1, 2, 4-triazol-3-yl) pyridine,

4- [5- (chloromethyl) -4-methyl-4H-1, 2, 4-triazol-3-yl ] pyridine,

4- (5- {2- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -4-cyclopropyl-4H-1, 2, 4-triazol-3-yl) pyridine,

4- (5- {2- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] -1-methylethyl } -4-cyclopropyl-4H-1, 2, 4-triazol-3-yl) pyridine,

4- (5- {2- [5- (5-chloro-2-fluorophenyl) -1, 2, 4-oxadiazol-3-yl ] propyl } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine,

4- (5- {2- [5- (5-chloro-2-fluorophenyl) -1, 2, 4-oxadiazol-3-yl ] propyl } -4-cyclopropyl-4H-1, 2, 4-triazol-3-yl) pyridine,

4- (4-methyl-5- {2- [5- (3-methylphenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -4H-1, 2, 4-triazol-3-yl) pyridine,

4- (4-cyclopropyl-5- { 1-methyl-2- [5- (3-methylphenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -4H-1, 2, 4-triazol-3-yl) pyridine,

3- (3-chloro-phenyl) -5- {2- [ 3-cyclopropyl-2- (4-methoxy-phenyl) -3H-imidazol-4 yl ] -ethyl } - [1, 2, 4] oxadiazole,

3- (3-chloro-phenyl) -5- {2- [ 3-cyclopropyl-2- (4-methoxy-phenyl) -3H-imidazol 4-yl ] -1-methyl-ethyl } - [1, 2, 4] oxadiazole,

4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -propyl } -1-cyclopropyl-1H-imidazol-2-yl) -pyridine,

3- (3-chloro-phenyl) -5- {2- [2- (4-methoxy-phenyl) -3-methyl-3H-imidazol 4-yl ] -1-methylethyl } - [1, 2, 4] oxadiazole,

(S)4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -propyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (5- { (2S) -2- [5- (3-chlorophenyl) -1, 3, 4-oxadiazol-2-yl ] propyl } -4-cyclopropyl-4H-1, 2, 4-triazol-3-yl) pyridine,

4- (5- { (2R) -2- [5- (3-chlorophenyl) -1, 3, 4-oxadiazol-2-yl ] propyl } -4-cyclopropyl-4H-1, 2, 4-triazol-3-yl) pyridine,

4- (5- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine,

5- (3-chlorophenyl) -3- ((1R) -1- { [ 4-methyl-5- (trifluoromethyl) -4H-1, 2, 4-triazol-3-yl ] oxy } ethyl) -1, 2, 4-oxadiazole,

3- (5- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethoxy } -4-cyclopropyl-4H-1, 2, 4-triazol-3-yl) pyridine,

3- (5- { (1R) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine,

5- (3-chlorophenyl) -3- ((1R) -1- { [5- (4-fluorophenyl) -4-methyl-4H-1, 2, 4-triazol-3-yl ] oxy } ethyl) -1, 2, 4-oxadiazole,

5- (3-chlorophenyl) -3- ((1R) -1- { [5- (3, 5-difluorophenyl) -4-methyl-4H-1, 2, 4-triazol-3-yl ] oxy } ethyl) -1, 2, 4-oxadiazole,

(+) -4- (5- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] propoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine,

(-)4- (5- { (1R) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine,

(+) -4- (5- { (1S) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine,

(-)4- (5- {1- [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine,

(+) -4- (5- {1- [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine,

4- (5- {1- [5- (3-chloro-phenyl) -isoxazol-3-yl ] -ethoxy } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

n- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -N, 4-dimethyl-5-pyridin-3-yl-4H-1, 2, 4-triazol-3-amine,

3-pyridin-4-yl-8- [1- (5-m-tolyl- [1, 2, 4] oxadiazol-3-yl) -ethyl ] -5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrimidine,

n, 4-dimethyl-N- { [5- (3-methylphenyl) -1, 2, 4-oxadiazol-3-yl ] methyl } -5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

n- { [5- (5-chloro-2-fluorophenyl) -1, 2, 4-oxadiazol-3-yl ] methyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

n- { [5- (4-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] methyl } -N-cyclopropyl-4-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

(+) -N- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -5- (3, 5-difluorophenyl) -N, 4-dimethyl-4H-1, 2, 4-triazol-3-amine,

(-) -N- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -5- (3, 5-difluorophenyl) -N, 4-dimethyl-4H-1, 2, 4-triazol-3-amine,

(+) -8- { (1S) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4] triazolo [4, 3-a ] pyrimidine,

(-) -8- { (1R) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl-3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4] triazolo [4, 3-a ] pyrimidine,

(-) -N- {1- [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

(+) -N- {1- [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

(-) -N- { (1S) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

(+) -N- { (1R) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

3- [5- (3-pyridin-4-yl-6, 7-dihydro-5H- [1, 2, 4] triazolo [4, 3- α ] pyrimidin-8-ylmethyl) - [1, 3, 4] oxadiazol-2-yl ] benzonitrile,

3- {5- [3- (2-methoxypyridin-4-yl) -6, 7-dihydro-5H- [1, 2, 4] triazolo [4, 3-a ] pyrimidin-8-ylmethyl ] [1, 3, 4] oxadiazol-2-yl } benzonitrile,

3- (5- { [ methyl- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -amino ] -methyl } - [1, 3, 4] oxadiazol-2-yl) benzonitrile,

3- {5- [3- (2-methoxy-pyridin-4-yl) -6, 7-dihydro-5H- [1, 2, 4] triazolo [4, 3- α ] pyrimidin-8-ylmethyl ] - [1, 2, 4] oxadiazol 3-yl } -benzonitrile,

3- {3- [ (3-pyridin-4-yl-6, 7-dihydro [1, 2, 4] triazolo [4, 3-a ] pyrimidin-8 (5H) -yl) methyl ] -1, 2, 4-oxadiazol-5-yl } benzonitrile,

3- (3- { [ [5- (2-methoxypyridin-4-yl) -4-methyl-4H-1, 2, 4-triazol-3-yl ] (methyl) amino ] methyl } -1, 2, 4-oxadiazol-5-yl) benzonitrile,

3- (3- { [ methyl (4-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-yl) amino ] methyl } -1, 2, 4-oxadiazol-5-yl) benzonitrile,

3- (3- { [3- (2-methoxypyridin-4-yl) -6, 7-dihydro [1, 2, 4] triazolo [4, 3-a ] pyrimidin-8 (5H) -yl ] methyl } -1, 2, 4-oxadiazol-5-yl) benzonitrile,

n- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

3- {5- [ (3-pyridin-4-yl-6, 7-dihydro [1, 2, 4] triazolo [4, 3-a ] pyrimidin-8 (5H) -yl) methyl ] -1, 2, 4-oxadiazol-3-yl } benzonitrile,

3- {5- [3- (2-hydroxy-pyridin-4-yl) -6, 7-dihydro-5H- [1, 2, 4] triazolo [4, 3- α ] pyrimidin-8-ylmethyl ] - [1, 2, 4] oxadiazol-3-yl } -benzonitrile,

n- { [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] methyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

n- { [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] methyl-4-cyclopropyl-N-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

[3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-ylmethyl ] -ethyl- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -amine,

n- { [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] methyl } -N-isopropyl-4-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

n- {1- [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] ethyl } -N-cyclopropyl-4-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

{1- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -ethyl } -methyl- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -amine,

[5- (3-chloro-phenyl) -isoxazol-3-ylmethyl ] -methyl (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -amine,

n- { [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] methyl } -4-cyclopropyl N-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

n- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] -1-methylethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

4- (5- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] -1-methylethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine,

N- { (1S) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -4-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine,

5- (3-chlorophenyl) -N-methyl-N- [ (4-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-yl) methyl ] -1, 2, 4-oxadiazol-3-amine,

5- (3-chlorophenyl) -N-ethyl-N- [ (4-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-yl) methyl ] -1, 2, 4-oxadiazol-3-amine,

[0167] ethyl-8- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4] triazolo [4, 3-a ] pyridine-8-carboxylate, and salts thereof.

[0168] More suitable examples of compounds of formula I are compounds represented by formula Ia

Wherein:

[0169]p is selected from hydrogen, C_3-7An alkyl or a 3-8 membered ring comprising one or more atoms independently selected from C, N, O and S, which ring may optionally be fused to a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S;

[0170]R¹selected from the group consisting of: hydrogen, hydroxy, halogen, nitro, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_1-6Alkyl radical, OC_1-6Alkyl radical, C_2-6Alkenyl radical, OC_2-6Alkenyl radical, C_2-6Alkynyl, OC_2-6Alkynyl, C_0-6Alkyl radical C_3-6Cycloalkyl radical, OC_0-6Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl, OC_0-6Alkylaryl, CHO, (CO) R ⁵，O(CO)R⁵，O(CO)OR⁵，O(CN)OR⁵，C_1-6Alkyl OR⁵，OC_2-6Alkyl OR⁵，C_1-6Alkyl (CO) R⁵，OC_1-6Alkyl (CO) R⁵，C_0-6Alkyl group CO₂R⁵，OC_1-6Alkyl group CO₂R⁵，C_0-6Alkylcyano, OC_2-6Alkylcyano radical, C_0-6Alkyl radical NR⁵R⁶，OC_2-6Alkyl radical NR⁵R⁶，C_1-6Alkyl (CO) NR⁵R⁶，OC_1-6Alkyl (CO) NR⁵R⁶，C_0-6Alkyl radical NR⁵(CO)R⁶，OC_2-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)NR⁵R⁶，C_0-6Alkyl SR⁵，OC_2-6Alkyl SR⁵，C_0-6Alkyl (SO) R⁵，OC_2-6Alkyl (SO) R⁵，C_0-6Alkyl SO₂R⁵，OC_2-6Alkyl SO₂R⁵，C_0-6Alkyl (SO)₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)NR⁵R⁶，C_0-6Alkyl radical NR⁵(SO₂)R⁶，OC_2-6Alkyl radical NR⁵(SO₂)R⁶，C_0-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，OC_2-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，(CO)NR⁵R⁶，O(CO)NR⁵R⁶，NR⁵OR⁶，C_0-6Alkyl radical NR⁵(CO)OR⁶，OC_2-6Alkyl radical NR⁵(CO)OR⁶，SO₂R⁵And a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S, wherein the ring may be substituted with one or more A;

[0171]M¹selected from the group consisting of: bond, C_1-3Alkyl radical, C_2-3Alkenyl radical, C_2-3Alkynyl, C_0-4Alkyl (CO) C_0-4Alkyl radical, C_0-3Alkyl OC_0-3Alkyl radical, C_0-3Alkyl (CO) NR⁵，C_0-3Alkyl (CO) NR⁵C_0-3Alkyl radical, C_0-4Alkyl radical NR⁵，C_0-3Alkyl group SC_0-3Alkyl radical, C_0-3Alkyl (SO) C_0-3Alkyl and C_0-3Alkyl (SO)₂)C_0-3An alkyl group;

[0172]R²selected from the group consisting of: hydrogen, hydroxy, C_0-6Alkyl cyano, oxo, ═ NR⁵，＝NOR⁵，C_1-4Alkyl halides, halogens, C_1-4Alkyl, O (CO) C_1-4Alkyl radical, C_1-4Alkyl (SO) C_0-4An alkyl group, a carboxyl group,C_1-4alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, OC_1-4Alkyl radical, C_1-4Alkyl OR⁵And C_0-4Alkyl radical NR⁵R⁶；

[0173]X¹、X²And X³Independently selected from the group consisting of CR, CO, N, NR, O and S;

[0174]r is selected from the group consisting of: hydrogen, C_0-3Alkyl, halogen, C_0-3Alkyl OR⁵，C_0-3Alkyl radical NR⁵R⁶，C_0-3Alkyl (CO) OR⁵，C_0-3Alkyl radical NR⁵R⁶And C_0-3An alkylaryl group;

[0175]M²Selected from the group consisting of: bond, C_1-3Alkyl radical, C_3-7Cycloalkyl radical, C_2-3Alkenyl radical, C_2-3Alkynyl, C_0-4Alkyl (CO) C_0-4Alkyl radical, C_0-3Alkyl OC_0-3Alkyl radical, C_0-3Alkyl radical NR⁵C_1-3Alkyl radical, C_0-3Alkyl (CO) NR⁵，C_0-4Alkyl radical NR⁵，C_0-3Alkyl group SC_0-3Alkyl radical, C_0-3Alkyl (SO) C_0-3Alkyl and C_0-3Alkyl (SO)₂)C_0-3An alkyl group;

[0176]R³selected from the group consisting of: hydrogen, hydroxy, C_0-6Alkyl cyano, oxo, ═ NR⁵，＝NOR⁵，C_1-4Alkyl halides, halogens, C_1-4Alkyl, O (CO) C_1-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, OC_1-4Alkyl radical, C_1-4Alkyl OR⁵And C_0-4Alkyl radical NR⁵R⁶；

[0177]X⁴Selected from the group consisting of: c_0-4Alkyl radical R⁵，C_0-4Alkyl (NR)⁵R⁶)，C_0-4Alkyl (NR)⁵r⁶＝N，NR⁵C_0-4Alkyl (NR)⁵R⁶)＝N，NOC_0-4Alkyl radical, C_1-4Alkyl halo, C, O, SO₂And S;

[0178] q is a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S, wherein the groups are optionally fused to a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S, wherein the fused ring may be substituted with one or more a;

[0179]R⁴selected from hydrogen, hydroxy, C_0-6Alkyl cyano, oxo, ═ NR⁵，＝NOR⁵，C_1-4Alkyl halides, halogens, C_1-4Alkyl radical, OC_1-4Alkyl radical, OC_0-6Alkylaryl, O (CO) C_1-4Alkyl radical, C_0-4Alkyl (S) C_0-4Alkyl radical, C_1-4Alkyl (SO) C_0-4Alkyl radical, C_1-4Alkyl (SO)₂)C_0-4Alkyl, (SO) C_0-4Alkyl group, (SO)₂)C_0-4Alkyl radical, C_1-4Alkyl OR⁵，C_0-4Alkyl radical NR ⁵R⁶And a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O or S, which ring may be substituted with one or more A;

[0180]R⁵and R⁶Independently selected from hydrogen, hydroxy, C_1-6Alkyl radical, C_0-6Alkyl radical C_3-6Cycloalkyl radical, C_0-6Alkylaryl group, C_0-6An alkylheteroaryl group and a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S, wherein R is⁵And R⁶May together form a 5-or 6-membered ring comprising one or more atoms independently selected from C, N, O and S;

[0181]wherein any one R¹、R²、R³、R⁴、R⁵And R⁶C under definition_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_0-6Alkyl radical C_3-6CycloalkanesBase, C_0-6Alkylaryl and C_0-6The alkylheteroaryl groups may all be substituted by one or more a;

[0182]a is selected from the following group: hydrogen, hydroxy, oxo, halogen, nitro, C_0-6Alkylcyano radical, C_1-4Alkyl radical, C_0-4Alkyl radical C_3-6Cycloalkyl radical, C_1-6Alkyl halo, OC_1-6Alkyl halo, C_2-6Alkenyl radical, OC_1-6Alkyl radical, C_0-3Alkylaryl group, C_0-6Alkyl OR⁵，OC_2-6Alkyl OR⁵，C_1-6Alkyl SR⁵，OC_2-6Alkyl SR⁵，(CO)R⁵，O(CO)R⁵，OC_2-6Alkylcyano radical, C_0-6Alkyl group CO₂R⁵，OC_1-6Alkyl group CO₂R⁵，O(CO)OR⁵，OC_1-6Alkyl (CO) R⁵，C_1-6Alkyl (CO) R⁵，NR⁵OR⁶，C_0-6Alkyl radical NR⁵R⁶，OC_2-6Alkyl radical NR⁵R⁶，C_0-6Alkyl (CO) NR⁵R⁶，OC_1-6Alkyl (CO) NR⁵R⁶，OC_2-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)R⁶，C_0-6Alkyl radical NR⁵(CO)NR⁵R⁶，O(CO)NR⁵R⁶，NR⁵(CO)OR⁶，C_0-6Alkyl (SO)₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)NR⁵R⁶，C_0-6Alkyl radical NR⁵(SO₂)R⁶，OC_2-6Alkyl radical NR⁵(SO₂)R⁶，SO₃R⁵，C_1-6Alkyl radical NR⁵(SO₂)NR⁵R⁶，OC_2-6Alkyl (SO)₂)R⁵，C_0-6Alkyl (SO)₂)R⁵，C_0-6Alkyl (SO) R⁵，OC_2-6Alkyl (SO) R⁵And a 5 or 6 membered ring comprising one or more atoms independently selected from C, N, O and S;

[0183] m is selected from 0, 1, 2, 3 and 4; and is

[0184] n is selected from 0, 1, 2 and 3,

[0185] or a salt thereof.

[0186] The present invention relates to the use of compounds of formula I and IA as defined above and salts thereof. The salts used in the pharmaceutical formulations should be pharmaceutically acceptable salts, while other salts may be used in the preparation of the compounds of formula I and Ia.

[0187] Examples of pharmaceutically acceptable salts include, but are not limited to, hydrochloride, 4-aminobenzoate, anthranilate, 4-aminosalicylate, 4-hydroxybenzoate, 3, 4-dihydroxybenzoate, 3-hydroxy-2-naphthoate, nitrate, and trifluoroacetate. Other pharmaceutically acceptable salts and methods for preparing such salts are described, for example, in Remington's Pharmaceutical Sciences (eighteenth edition, Mack publishing Co.).

[0188] Some of the compounds of formula I may have chiral and/or geometric centres (E-and Z-isomers) and it is therefore to be understood that the present invention encompasses all such optical, diastereoisomers and geometric isomers.

[0189] The present invention relates to any and all tautomeric forms of the compounds of formula I.

[0190] The present invention relates to the following compounds which may be used as intermediates in the preparation of compounds of formula I:

6-methyl pyridine-4-formic acid,

1-cyano-3-ethyl benzene, and a pharmaceutically acceptable salt thereof,

3-Ethylbenzoic acid

3-fluoro-5-methylbenzoic acid

3-methoxy-methyl-benzoic acid, which is a compound of formula (I),

n-hydroxy-3-methoxy-benzamidine,

(ii) an N-hydroxy-benzamidine,

n-hydroxy-3-methyl-benzamidine,

5-chloromethyl-3- (3-methoxy-phenyl) - [1, 2, 4] oxadiazole

5-chloromethyl-3-phenyl- [1, 2, 4] oxadiazole

5-chloromethyl-3-m-tolyl- [1, 2, 4] oxadiazole

3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -benzonitrile,

3- (5-chloromethyl- [1, 2, 4] oxadiazol-3-yl) -benzonitrile,

3-chloromethyl-5-m-tolyl [1, 2, 4] oxadiazole

3-chloromethyl 5- (3-fluoro-phenyl) - [1, 2, 4] oxadiazole

3-chloromethyl-5-thiophen-3-yl [1, 2, 4] oxadiazole

3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -5-methylpyridine,

3-chloromethyl-5- (3-nitro-phenyl) - [1, 2, 4] oxadiazole,

4- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -2-methylpyridine,

3-chloromethyl-5- (3-ethyl-phenyl) - [1, 2, 4] oxadiazole,

3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -phenyl ] -dimethyl-amine,

3-chloromethyl-5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5- (3-trifluoromethoxy-phenyl) - [1, 2, 4] oxadiazole

5- (3-bromo-phenyl) -3-chloromethyl [1, 2, 4] oxadiazole,

3-chloromethyl-5-thiophen-2-yl- [1, 2, 4] oxadiazole,

3-chloromethyl-5- (3-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5-thiazol-4-yl- [1, 2, 4] oxadiazole,

3-chloromethyl-5- (3-iodo-phenyl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5- (3-methoxymethyl-phenyl) - [1, 2, 4] oxadiazole,

5-furan-2-yl-4-methyl-4H- [1, 2, 4] triazole-3-thiol,

4-methyl-5-phenyl-4H- [1, 2, 4] triazole-3-thiol,

4-methyl-5-pyridin-2-yl-4H- [1, 2, 4] triazol-3-thiol,

5- (4-benzyl-morpholin-2-yl) -4-methyl-4H- [1, 2, 4] triazole-3-thiol,

5-tert-butyl-4-methyl-4H- [1, 2, 4] triazole-3-thiol,

4-methyl-5-pyridin-3-yl-4H- [1, 2, 4] triazol-3-thiol,

4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazole-3-thiol,

4-methyl-5-thiazol-4-yl-4H- [1, 2, 4] triazol-3-thiol,

5-cyclohexyl-4-methyl-4H- [1, 2, 4] triazole-3-thiol,

5-chloro-thiophene-3-carboxylic acid,

3-methylthio-benzoic acid, which is,

3-cyclopropyl-benzoic acid, a salt thereof,

3-tert-butoxycarbonylamino-benzoic acid,

3-acetyl-benzoic acid, a salt thereof,

2-methyl-isonicotinyl hydrazine,

5-chloro-2-fluoro-benzoyl hydrazine,

3-cyano-benzoyl hydrazine is used as a chelating agent,

2-chloro-isonicotinyl hydrazine,

2-fluoro-5-methyl-benzoyl hydrazine,

a pyrimidine-4-carboxylic acid hydrazide which,

3-fluoro-N-hydroxy-benzamidine,

n-hydroxy-thiophene-3-carboxamidine,

2-chloro-N-hydroxy-propionamidine,

3, N-dihydroxy-benzamidine,

n-hydroxy-2-methyl-benzamidine,

n-hydroxy-2- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -acetamidine,

3-chloro-N-hydroxy-benzamidine,

2, 5-difluoro-N-hydroxy-benzamidine,

4-methyl-5-pyridin-3-yl-4H- [1, 2, 4] triazol-3-thiol,

4-butyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole-3-thiol,

4- (3-methoxypropyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-thiol,

4-benzyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole-3-thiol,

4-furan-2-ylmethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-thiol,

5-thiophen-2-yl-4-thiophen-2-ylmethyl-4H- [1, 2, 4] triazol-3-thiol,

4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole-3-thiol,

4-furan-2-ylmethyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-thiol,

4-ethyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-thiol,

4-ethyl-5-pyridin-3-yl-4H- [1, 2, 4] triazol-3-thiol,

4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole-3-thiol,

4-furan-2-ylmethyl-5-pyridin-3-yl-4H- [1, 2, 4] triazol-3-thiol,

4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5- (3-fluoro-phenyl) -4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5- (4-fluoro-phenyl) -4H- [1, 2, 4] triazole-3-thiol,

5- (2-fluoro-5-methyl-phenyl) -4-furan-2-ylmethyl-4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5- (3-methyl-thiophen-2-yl) -4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5- (5-methyl-thiophen-2-yl) -4H- [1, 2, 4] triazole-3-thiol,

5- (2-chloro-6-methylpyridin-4-yl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

5- (5-bromo-furan-2-yl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5- (3-methoxythiophene-2-yl) -4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5- (tetrahydro-furan-2-yl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5-thio-4, 5-dihydro-1H- [1, 2, 4] triazole-3-carboxylic acid methyl ester,

5- (2-chloro-pyridin-4-yl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

5- (2-chloro-6-methoxy-pyridin-4-yl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5- (3-methyl-3H-imidazol-4-yl) -4H- [1, 2, 4] triazole-3-thiol,

4-propyl-5-pyridin-4-yl-4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5- (1-methyl-1H-imidazol-2-yl) -4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5- (1-methyl-1H-imidazol-4-yl) -4H- [1, 2, 4] triazole-3-thiol,

3- (5-mercapto-4-methyl-4H- [1, 2, 4] triazol-3-yl) -benzonitrile,

5- (3-chloro-phenyl) -4-methyl-4H- [1, 2, 4] triazole-3-thiol,

5- (4-chloro-phenyl) -4-methyl-4H- [1, 2, 4] triazole-3-thiol,

5- (2-fluoro-phenyl) -4-methyl-4H- [1, 2, 4] triazole-3-thiol,

5- (3-fluoro-phenyl) -4-methyl-4H- [1, 2, 4] triazole-3-thiol,

5- (4-fluoro-phenyl) -4-methyl-4H- [1, 2, 4] triazole-3-thiol,

5-benzo [ b ] thiophen-2-yl-4-methyl-4H- [1, 2, 4] triazole-3-thiol,

5- (3-methoxyphenyl) -4-methyl-4H- [1, 2, 4] triazole-3-thiol,

5- (4-methoxyphenyl) -4-methyl-4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4] triazole-3-thiol,

5- (3, 5-difluoro-phenyl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

5- (2, 6-difluoro-phenyl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

5- (4-butoxyphenyl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

5-benzo [1, 3] dioxol-5-yl-4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5-pyrimidin-5-yl 2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5-furan-3-yl 2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4- (tetrahydrofuran-2-ylmethyl) -5-thiophen-2-yl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

5-cyclopentyl-4-ethyl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5- [2- (4-methoxy-phenyl) -ethyl ] -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

5- (3, 5-dichloro-phenyl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

5- (3-methylphenyl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

5- (4-methylphenyl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5- (3-nitrophenyl) -4H- [1, 2, 4] triazole-3-thiol,

5- (2, 5-difluorophenyl) -4-ethyl-4- [1, 2, 4] triazole-3-thiol,

5- (3-chlorophenyl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

5- (4-chlorophenyl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-5-methoxymethyl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-methyl-5-pyridin-4-yl 2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-allyl-5-furan-2-yl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5- (4-methoxy-phenoxymethyl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5-phenoxymethyl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5-hydroxymethyl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5- (2-methoxy-ethyl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5-methylthiomethyl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

5-ethoxymethyl-4-ethyl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

5-furan-3-yl-4-methyl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-methyl-5-pyrimidin-4-yl-2, 4-dihydro [1, 2, 4] triazole-3-thione,

4-ethyl-5-pyridazin-4-yl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5-pyridin-4-ylmethyl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5- (6-hydroxy-pyridin-3-yl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5- (4-hydroxy-phenyl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5-p-tolyloxymethyl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5- (6-methoxy-pyridin-3-yl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5- (2-methoxy-pyridin-4-yl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5-pyrimidin-2-yl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5- (5-methoxy-pyrimidin-2-yl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-furan-2-ylmethyl-4H- [1, 2, 4] triazole-3-thiol,

4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-thiol,

4-cyclopropylmethyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-thiol,

4-cyclopropyl-5-thiophen-2-yl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

5-furan-2-yl-4- (2-methoxy-ethyl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-cyclopropyl-5-furan-2-yl 2, 4-dihydro- [1, 2, 4] triazole-3-thione,

(3-thien-2-yl-5-thio-1, 5-dihydro- [1, 2, 4] triazol-4-yl) -acetic acid methyl ester,

4-cyclopropylmethyl-5-thiophen-2-yl 2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4- (2-methoxyethyl) -5-thiophen-2-yl 2, 4-dihydro- [1, 2, 4] triazole-3-thione,

thien-2-yl-4- (2, 2, 2-trifluoroethyl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-cyclopropyl-5-pyrimidin-4-yl 2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-cyclopropyl-5-pyridin-3-yl-2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazole-3-thiol,

4-ethyl-3-methanesulfonyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole,

4- (5-methanesulfonyl-4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

4- (2-hydroxy-ethyl) -5-thiophen-2-yl 2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4- (4, 5-dimethyl-4H- [1, 2, 4] triazol-3-yl) -pyridine,

methyl- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -amine,

3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrimidine,

3-furan-2-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrimidine,

4-ethyl-5- (6-methoxy-pyridazin-3-yl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

4-ethyl-5- (5-methoxy-pyridin-2-yl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione,

5-chloromethyl-3-phenyl- [1, 2, 4] oxadiazole,

5-chloromethyl-3- (3-fluoro-phenyl) - [1, 2, 4] oxadiazole,

5-chloromethyl-3- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazole,

5-chloromethyl-3-thiophen-2-yl [1, 2, 4] oxadiazole,

5-chloromethyl-3-thiophen-3-yl- [1, 2, 4] oxadiazole,

3- (5-chloromethyl- [1, 2, 4] oxadiazol-3-yl) -phenol,

5-chloromethyl-3-o-tolyl- [1, 2, 4] oxadiazole,

5-chloromethyl-3- (3-chloro-phenyl) - [1, 2, 4] oxadiazole,

5-chloromethyl-3- (2, 5-difluoro-phenyl) - [1, 2, 4] oxadiazole,

3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -benzonitrile,

2-chloro-4- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -pyridine,

3-chloromethyl-5- (2, 5-dimethyl-phenyl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5- (2, 5-dichloro-phenyl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5- (2-fluoro-5-bromo-phenyl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5- (3-methyl-phenyl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5- (2, 5-difluoro-phenyl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5- (3-methylsulfanyl-phenyl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5- (3-cyclopropyl-phenyl) - [1, 2, 4] oxadiazole,

3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -phenyl ] -carbamic acid tert-butyl ester,

1- [3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -phenyl ] -ethanone,

5- (5-chloro-2-fluoro-phenyl) -3-chloromethyl- [1, 2, 4] oxadiazole,

2- (3-chloromethyl [1, 2, 4] oxadiazol-5-yl) -4-methyl-phenol,

3-chloromethyl 5- (2-chloro-5-methyl-phenyl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5- (2, 5-dichloro-thiophen-3-yl) - [1, 2, 4] oxadiazole,

3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -benzonitrile,

3-chloromethyl-5- (3-fluoro-phenyl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5- (2-methyl-thiazol-4-yl) - [1, 2, 4] oxadiazole,

3-chloromethyl-5- (4-fluoro-phenyl) - [1, 2, 4] oxadiazole,

5- (5-bromo-2-fluoro-phenyl) -3-chloromethyl- [1, 2, 4] oxadiazole,

3-chloromethyl-5- (4-methyl-thiophen-2-yl) - [1, 2, 4] oxadiazole,

5- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -thiophene-3-carbonitrile,

2- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -4-methyl-benzonitrile,

3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -5-fluoro-benzonitrile,

3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -4-fluoro-benzonitrile,

4-chloro-2- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -phenol,

3- (1-chloro-ethyl) -5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole,

3- (1-chloro-ethyl) -5- (3-fluoro-phenyl) - [1, 2, 4] oxadiazole,

3- (1-chloro-ethyl) -5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazole,

[3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -phenyl ] -methanol,

3-chloromethyl-5- [1- (toluene-4-sulfonyl) -1H-pyrrol-3-yl ] - [1, 2, 4] oxadiazole,

3-chloromethyl-5-furan-3-yl- [1, 2, 4] oxadiazole,

3-chloromethyl-5- (5-chloro-thiophen-2-yl) - [1, 2, 4] oxadiazole,

1- [5- (3-chlorophenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethanol,

[5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -methanol,

1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethanol,

[5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] -methanol,

2-chloromethyl-5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] diazole,

2-chloromethyl-5- (3-fluoro-phenyl) - [1, 3, 4] oxadiazole,

4- (5-chloromethyl- [1, 3, 4] oxadiazol-2-yl) -2-methyl-pyridine,

2-chloromethyl-5-m-tolyl- [1, 3, 4] oxadiazole,

3- (5-chloromethyl- [1, 3, 4] oxadiazol-2-yl) -benzonitrile,

2-chloro-4- (5-chloromethyl- [1, 3, 4] oxadiazol-2-yl) -pyridine,

2- (5-chloro-2-fluoro-phenyl) -5-chloromethyl- [1, 3, 4] oxadiazole,

2- (1-bromo-ethyl) -5- (3-chloro-phenyl) - [1, 3, 4] oxadiazole,

2- (1-bromo-ethyl) -5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4] oxadiazole,

4- [5- (1-bromo-ethyl) - [1, 3, 4] oxadiazol-2-yl ] -2-methyl-pyridine,

2- (1-bromo-ethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] oxadiazole,

2- (1-bromo-ethyl) -5- (3-chloro-phenyl) - [1, 3, 4] oxadiazole,

3- (1-bromo-ethyl) -5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole,

1- [5- (3-chlorophenyl) -isoxazol-3-yl ] -ethanol,

1- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl ] -ethanol,

5- (2-fluoro-5-methyl-phenyl) -isoxazole-3-carboxylic acid methyl ester,

5-thiophen-3-yl-isoxazole-3-carboxylic acid methyl ester,

5-phenyl-isoxazole-3-carboxylic acid methyl ester,

5- (3-chloro-phenyl) -4-methyl-isoxazole-3-carboxylic acid ethyl ester,

5- (5-chloro-thiophen-3-yl) -isoxazole-3-carboxylic acid methyl ester,

[5- (3-chloro-phenyl) -isoxazol-3-yl ] -methanol,

[2- (3-chloro-phenyl) -oxazol-4-yl ] -methanol,

[3- (3-chloro-phenyl) -isoxazol-5-yl ] -methanol,

5- (thien-3-yl-isoxazol-3-yl) methanol,

[5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl ] -methanol,

(5-phenyl-isoxazol-3-yl) -methanol,

[5- (3-chloro-phenyl) -4-methyl-isoxazol-3-yl ] -methanol,

[5- (5-chloro-thiophen-3-yl) -isoxazol-3-yl) ] -methanol,

methanesulfonic acid 1- [5- (3-chloro-phenyl) -isoxazol-3-yl ] -ethyl ester,

methanesulfonic acid 2- (3-chloro-phenyl) -oxazol-4-ylmethyl ester,

methanesulfonic acid 3- (3-chloro-phenyl) -isopyrrol-5-ylmethyl ester,

methanesulfonic acid 5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-ylmethyl ester,

methanesulfonic acid-phenyl) -isoxazol-5-yl ] -ethyl ester,

methanesulfonic acid 5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-ylmethyl ester,

methanesulfonic acid 5- (3-chloro-phenyl) -isoxazol-3-ylmethyl ester,

methanesulfonic acid 5-thiophen-3-yl-isoxazol-3-ylmethyl ester,

Methanesulfonic acid 5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-ylmethyl ester,

methanesulfonic acid 5-phenyl-isoxazol-3-ylmethyl ester,

methanesulfonic acid 5- (3-chloro-phenyl) -4-methyl-isoxazol-3-ylmethyl ester,

methanesulfonic acid 5- (5-chloro-thiophen-3-yl) -isoxazol-3-ylmethyl ester,

methanesulfonic acid 1- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl ] -ethyl ester,

methanesulfonic acid 1- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl ] -ethyl ester,

methanesulfonic acid 4-chloro-5- (3-chloro-phenyl) -isoxazol-3-ylmethyl ester,

the reaction product of pyrimidine-4-carboxylic acid,

3- (3-chloro-phenyl) -isoxazole-5-carboxylic acid methyl ester,

2-bromomethyl-5- (3-chloro-phenyl) -oxazole,

2- (3-chloro-phenyl) -oxazole-4-carboxylic acid methyl ester,

1- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl ] -ethanol,

1- [3- (3-chloro-phenyl) -isoxazol-5-yl ] -ethanol,

[5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl ] -methanol,

3- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -propionylhydrazide,

3- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -butyryl-hydrazine,

3- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -alanine ethyl ester hydrochloride,

3- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -propionylhydrazide,

[5- (3-chloro-phenyl- [1, 2, 4] oxadiazol 3-yl ] -acethydrazide,

(R) -3- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -butyryl hydrazine,

3- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -3-methyl-butyryl hydrazine,

3- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -piperidin-2-one,

3- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -piperidin-2-one,

3-chloromethyl-5- (5-chloro-thiophen-3-yl) - [1, 2, 4] oxadiazole,

1- [5- (5-chloro-thiophen-3-yl) - [1, 2, 4] oxadiazol-3-ylmethoxy ] -1H-benzotriazole,

(4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -acetonitrile,

2- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -propionic acid,

2- (4-methyl-5-pyridin-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -propionic acid,

3- (3-chloro-phenyl) -5- (4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole, or

{3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl-phenyl } -carbamic acid tert-butyl ester.

Pharmaceutical preparation

[0191] One aspect of the present invention is to provide a pharmaceutical formulation comprising a compound of formula I or a salt thereof, for use in the prevention and/or treatment of a disorder mediated by the metabotropic glutamate receptor subtype 5 receptor (mGluR5), or any of the following.

[0192] The compositions may be in a form suitable for oral administration, for example as tablets, pills, syrups, powders, granules or capsules, sterile solutions, suspensions or emulsions for parenteral injection (including intravenous, subcutaneous, intramuscular, intravascular injections or infusions), ointments, patches or creams suitable for topical administration or suppositories suitable for rectal administration.

[0193] In general, the above compositions may be prepared in conventional manner using one or more conventional excipients, pharmaceutically acceptable diluents and/or inert carriers.

[0194] Another aspect of the present invention provides a pharmaceutical formulation comprising as active ingredient a therapeutically effective amount of a compound of formula I in combination with one or more pharmaceutically acceptable diluents, excipients and/or inert carriers.

[0195] Suitable daily dosages for treating mammals, including humans, with a compound of formula I are from about 0.01 to 250mg/kg body weight for oral administration and from about 0.001 to 250mg/kg body weight for parenteral administration. The usual daily dosage of the active ingredients varies within wide limits depending on various factors such as the relevant indication, the route of administration, the age, weight and sex of the patient and may be determined by a physician.

Medical application

[0196] The compounds of the present invention or salts thereof have been found to exhibit a high degree of potency and selectivity for individual metabotropic glutamate receptor (mGluR) subtypes. The compounds of the invention are particularly potent and selective for group I mGluR receptors, more particularly with respect to mGluR 5. Accordingly, the compounds of formula I of the present invention are expected to be useful for the prevention and/or treatment of disorders associated with excitatory activation of group I mGluR receptors and for inhibiting neuronal damage caused by excitatory activation of group I mGluR receptors, particularly group I mGluR receptor at mGluR 5. These compounds may be used to generate inhibition of group I mglurs, particularly mGluR5, in mammals including humans.

[0197] mGluR5 is highly expressed in the central and peripheral nervous systems, as well as in other tissues. Thus, the compounds of the present invention are expected to be well suited for the prevention and/or treatment of mGluR5 receptor mediated disorders such as acute and chronic neurological and psychiatric disorders and chronic and acute pain.

[0198] Other diseases are Alzheimer's disease, senile dementia, AIDS-induced dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's chorea, migraine, epilepsy, schizophrenia, depression, anxiety, acute anxiety, obsessive compulsive disorder, ophthalmological diseases such as retinopathy, diabetic retinopathy, glaucoma, otic neurological disorders such as tinnitus, chemotherapy-induced neuropathy, postherpetic neuralgia and trigeminal neuralgia, tolerance, dependence, addiction and craving disorders, neurodevelopmental disorders including Fragile X, autism, mental retardation, schizophrenia and Down's syndrome.

[0199] The compounds are also suitable for the prevention and/or treatment of pain associated with migraine, inflammatory pain, neuropathic pain including diabetic neuropathy, arthritis and rheumatic diseases, low back pain, post-operative pain and pain associated with a variety of conditions including angina, renal or gallbladder colic, menstruation, migraine and gout.

[0200] Other conditions are stroke, head trauma, anoxic and ischemic trauma, hypoglycemia, cardiovascular disease and epilepsy.

[0201] The dosage required for the therapeutic or prophylactic treatment of a particular disease will necessarily vary depending upon the host treated, the route of administration and the severity of the disease being treated.

[0202] The present invention relates to compounds of formula I as defined above for use in therapy.

[0203] The present invention relates to the use of compounds of formula I as defined above for the prevention and/or treatment of neurological diseases.

[0204] The present invention relates to the use of compounds of formula I as defined above for the prevention and/or treatment of psychiatric disorders.

[0205] The present invention relates to the use of compounds of formula I as defined above for the prevention and/or treatment of chronic and acute pain disorders.

[0206] The present invention relates to the use of compounds of formula I as defined above for the prevention and/or treatment of mGluR5 receptor mediated disorders.

[0207] The present invention relates to the use of compounds of formula I as defined above for the prevention and/or treatment of alzheimer's disease, senile dementia, AIDS-induced dementia, parkinson's disease, amyotrophic lateral sclerosis, huntington's chorea, migraine, epilepsy, schizophrenia, depression, anxiety, acute anxiety, ophthalmological diseases such as retinopathy, diabetic retinopathy, glaucoma, otic neurological disorders such as tinnitus, chemotherapy-induced neuropathy, postherpetic neuralgia and trigeminal neuralgia, tolerance, dependence, Fragile X, autism, mental retardation, schizophrenia and down syndrome.

[0208] The present invention relates to the use of compounds of formula I as defined above for the prevention and/or treatment of pain associated with migraine, inflammatory pain, neuropathic pain including diabetic neuropathy, arthritis and rheumatic diseases, low back pain, post-operative pain and pain associated with a variety of conditions including angina, renal or gallbladder colic, menstruation, migraine and gout.

[0209] The present invention relates to the use of compounds of formula I as defined above for the prevention and/or treatment of stroke, head trauma, anoxic and ischemic trauma, hypoglycemia, cardiovascular diseases and epilepsy.

[0210] The present invention relates to the use of compounds of formula I and formula II for the treatment of gastrointestinal disorders.

[0211] Other embodiments of the present invention relate to the use of compounds of formula I and formula II for the preparation of a medicament for the inhibition of transient lower esophageal sphincter relaxations, for the preparation of a medicament for the treatment of GERD, for the preparation of a medicament for the prevention of gastrointestinal reflux, for the preparation of a medicament for the treatment of regurgitation, for the treatment of asthma, for the treatment of laryngitis, for the treatment of pulmonary disorders and for modulating stunted development.

[0212] The invention also relates to the use of a compound of formula I as defined above for the preparation of a medicament for the prevention and/or treatment of mGluR5 receptor mediated disorders and any other disorder listed above.

[0213] The invention also provides a method of treatment and/or prevention of mGluR5 mediated disorders and any of the disorders listed above, comprising administering to a subject suffering from or at risk of suffering from an effective amount of a compound of formula I as described above.

[0214] In the context of the present invention, the term "treatment" includes both treatment and prophylaxis, unless specifically indicated to the contrary. The terms "therapeutic" and "therapeutically" are to be construed accordingly.

[0215] In this specification, unless otherwise indicated, the term "antagonist" means a compound that, by any means, partially or completely blocks the transduction pathway leading to the ligand producing response.

[0216] Unless otherwise indicated, the term "disease" means any of a variety of conditions or diseases associated with metabotropic glutamate receptor activity.

Non-medical use

[0217] In addition to their therapeutic utility as pharmaceuticals, the compounds of formula I or salts thereof are also useful as pharmacological tools for the development and standardization of in vitro and in vivo test systems for assessing the effects of mGluR-related activity inhibitors in laboratory animals such as cats, dogs, rabbits, monkeys, rats and mice, as part of the development of new therapeutic agents.

Pharmacology of

[0218]The pharmacological properties of the compounds of the invention can be assayed using standard assays for functional activity. For example, in Aramori et al, Neuron 8: 757(1992), Tanabe et al, Neuron 8: 169(1992), Miller et al, J.neuroscience 15: 6103(1995), Balazs, et al, j. neurochemistry 69: 151(1997) are well known in the art. The methodologies described in these publications are incorporated herein by reference. Suitably, [ Ca ] expressing mGluR5 intracellularly by measuring intracellular calcium mobilisation²⁺]_iCan study the inventionA compound (I) is provided.

[0219] Intracellular calcium mobilization is measured by detecting changes in fluorescence of cells loaded with the fluorescent indicator, fluoro-3. The fluorescence signal was measured using a FLIPR system (molecular device). A two-addition assay is used to detect compounds that either activate or antagonize the receptor.

[0220]For FLIPR assay, cells expressing human mGluR5d were seeded in collagen-coated 96-well plates with clear bottom and black sides [ Ca ] 24 hours after seeding²⁺]_iAnd (5) performing mobilization analysis.

[0221] FLIPR experiments were performed using a 0.800W laser device and 0.4 second CCD camera shutter speed. Each FLIPR experiment was started by injecting 160 μ L of buffer into each well of the cell plate. After each addition of compound, the fluorescence signal was sampled 50 times at 1 second intervals, followed by 3 times at 5 second intervals. The highest point of the response peak during sampling was taken as the measured response value.

[0222]EC was determined from data obtained from a repeatedly performed 8-point Concentration Response Curve (CRC)₅₀And IC₅₀. CRC for an agonist was generated by measuring the response of all the maximal effects observed from the well plate. Agonist challenge for antagonist blockade the average response of agonist challenge in 14 control wells on the same well plate was taken as a criterion.

[0223]We have demonstrated that Inositol Phosphates (IP)₃) Flip-based assay for secondary function of mGluR5 d. IP as an index of phospholipase C turnover-mediated receptors₃Accumulation of (2). By [3H ]]Inositol GHEK cells stably expressing the human mGluR5d receptor were incubated overnight, washed 3 times in HEPES buffered saline, and preincubated with 10mM LiCl for 10 min. Compounds (agonists) were added and incubated at 37 ℃ for 30 min. Antagonist activity was determined by preincubating the test compounds for 15 minutes, followed by incubation in the presence of glutamate (80 μ M) or DHPG (30 μ M) for 30 minutes. The reaction was stopped by adding perchloric acid (5%). The samples were collected and neutralized and inositol phosphates were separated using a Gravity-Fed ion exchange column.

[0224] The following pharmaceutical examples illustrate detailed experimental designs for testing compounds of the present invention.

[0225] Abbreviations

FLIPR fluorescent imaging plate reader

CCD charge coupled device

CRC concentration response curve

Human embryonic kidney expressing glutamic acid transporter for GHEK

HEPES 4- (2-hydroxyethyl) -1-piperazineethanesulfonic acid (buffer)

IP3 inositol triphosphate

DHPG 3, 5-dihydroxyphenyl glycine;

BSA bovine serum albumin

EDTA ethylene diamine tetraacetic acid

Preparation method

[0226] In another aspect, the invention provides a process for preparing a compound of formula I or a salt thereof.

[0227] This process can be understood by referring to all of the following descriptions: where appropriate, addition of suitable protecting groups followed by removal from the various reactants and intermediates; in a sense, this is readily understood by those skilled in the art of organic synthesis. Conventional protocols using such protecting Groups, as well as examples of suitable protecting Groups, are described, for example, "Protective Groups in Organic Synthesis" T.W.Green, P.G.M.Wuts, Wiley-Interscience, New York, 1999. It can also be understood that: on any intermediate or end product in the pathway to the end product synthesis, one group or substituent can be converted to another by chemical manipulation, with the possible types of conversion being limited only by the inherent incompatibility of the other functionalities carried by the molecule at this stage with the conditions and reactants used for the conversion. Such inherent incompatibility, and the manner in which applicable switching and synthesis steps are carried out in the proper order to prevent this, will be readily understood by those skilled in the art of organic synthesis. Examples of transformations are given below, and it will be understood that the transformations described are not limited to the general illustrated groups or substituents of transformations. References and descriptions of other suitable Transformations are provided in "Comprehensive Organic Transformations-A Guide to functional groups precursors" R.C. Larock, VHC Publishers, Inc. (1989). Other suitable references and descriptions of reactions are described in textbooks of organic chemistry, for example "Advanced organic chemistry", March, fourth edition McGraw Hill (1992) or "organic Synthesis", Smith, McGraw Hill (1994). Techniques for purifying intermediates and final products include, for example, forward and reverse phase chromatography on columns or rotating plates, recrystallization, distillation, and liquid-liquid or solid-liquid extraction; as will be readily understood by those skilled in the art. Except where otherwise defined, the groups or substituents are as defined for formula I. Unless otherwise stated, the terms "room temperature" and "ambient temperature" mean a temperature of 16 to 25 ℃.

[0228]P, Q, X unless otherwise stated¹、X²、X³、X⁴、R、R¹、R²、R³、R⁴、R⁵、R⁶、M¹、M²M and n are as defined for formula I.

[0229] All raw materials are commercially available or described earlier in the literature.

[0230]For the¹H and¹³c NMR spectra, recorded using a Bmker 300, Bruker DPX400 or Varian +400 spectrometer at 300, 400 and 400MHz operation, respectively, using TMS or residual solvent signal as reference in deuterated chloroform as solvent, unless otherwise indicated¹H and¹³c nuclear magnetic resonance spectroscopy. All reported chemical shifts appear in the log as a fine split of the ppm signal above the δ measurement. (s: singlet, d: doublet, t: triplet t, q: quartetPeak, m: multiple peaks).

[0231] The liquid chromatographic separation of the on-line analysis and subsequent mass spectrometric detection were recorded on a Waters LCMS consisting of an Alliance2795(LC) and ZQ single quadrupole mass spectrometer. The mass spectrometer was equipped with an electrospray ion source, operating in either the positive or negative ion mode. The ion spray voltage was 3kV and the mass spectrometer was scanned from 100-700m/z at a scan time of 0.8 s. A linear gradient of 5% to 100% acetonitrile in 10mM ammonium acetate (aq.) or 0.1% TFA (aq.) was applied to a column X-Terra MS, Waters, C8, 2.1X 50mM, 3.5 μm.

[0232] Preparative reverse phase chromatography was run on HPLC with a diode array detector Gilson automated prep using a column XTerra MS C8, 19X 300mm, 7 μm.

[0233] MS-triggered preparative reverse phase chromatography was run on a Waters automated purified LC-MS system with a diode array detector and ZQ mass detector using a column XTerra MSC8, 19X 100mm, 5 μm.

[0234] Centrifugal thin layer chromatography was performed on rotating silica gel/gypsum (Merck, 60 PF-254 with calcium sulfate) coated glass slides with a thickness of 1.2 or 4mm using TC Research 7924T centrifugal thin layer chromatography.

[0235] Purification of the product was performed using a chemical elution extraction column (Varian, cat # 1219-.

[0236] Microwave heating was performed in a Smith synthesizer single mode microwave cavity, producing continuous illumination at 2450MHz (Personal Chemistry AB, Uppsala, Sweden).

[0237] Abbreviations:

atm atmospheric pressure

aq. method of water

CDI N, N' -formyl diimidazoles

d days

DBU 1, 8-diazabicyclo [5.4.0] undec-7-ene

DCC N, N-dicyclohexylcarbodiimide

DCM dichloromethane

DEA N, N-diisopropylethylamine

DIC N, N' -diisopropylcarbodiimide

DMAP N, N-dimethyl-4-aminopyridine

DMF N, N-dimethylformamide

DMSO dimethyl sulfoxide

EA Ethyl acetate

BOPA benzoyl peroxide

EDCl N- [3- (dimethylamino) propyl ] -N' -ethylcarbodiimide hydrochloride

EtOH ethanol

Et₂O diethyl ether

h hours

hep heptane

hex Hexane

P-BEMP polystyrene in combination with 2-tert-butylimino-2-diethylamino-1, 3-dimethyl-perhydro-1, 3, 2-diazaphosphocyclohexene (diazaphosphorine)

Deoxyfluor [ bis (2-methoxyethyl) amino ] thio-trifluoride

DAST (diethylamino) sulfur trifluoride

EDCI 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride

HOBt 1-hydroxybenzotriazole hydrate

THF tetrahydrofuran

TFA trifluoroacetic acid

Et Ethyl group

Ac acetyl group

DIBAL diisobutyl aluminum hydride

M, N mol and equivalent

MeOH methanol

HBTU O-benzotriazol-1-yl-N, N, N ', N' -tetramethyluronium hexafluorophosphate

Salt (salt)

Boc tert-butyloxycarbonyl oxygen

HMDS hexamethyldisilazane

Ms methanesulfonyl or methanesulfonyl

min for

NADPH nicotinamide adenine dinucleotide phosphate reduced form

nBuLi 1-butyl lithium

NBS N-bromosuccinimide

Novozyme 435 ® Polymer-supported trademark name of Candida antarctica

o.n. overnight

preparation of prep

r.t. or rt room temperature

sat, saturated

TEA Triethylamine

LDA lithium diisopropylamide

LHA lithium aluminium hydride

MCPBA m-chloroperoxybenzoic acid

SPE solid extraction

Lawesson's reagent [2, 4-bis (4-methoxyphenyl) -1, 3-dithia-2, 4-diphosphetane-2, 4-disulfide

TFA trifluoroacetic acid

Ts tosyl or p-tosyl

[0238] General Synthesis of Compounds of formula V

[0239]A compound of formula V wherein R⁷Independently selected from M¹-(R²)_n-P-(R¹)_m1、M²-(R³)_n-X⁴-Q-(R⁴)_m2And M²-(R³)_n-G, wherein G is a leaving group or a group which can subsequently be converted into a leaving group. The compound of formula V may be prepared by reacting an appropriately activated compound of formula III with a compound of formula II to form a compound of formula IV, followed by cyclization of the compound of formula IV; wherein LG of formula III is a leaving group. The compounds of formula II can be prepared from the appropriate nitrile by addition of hydroxylamine in a suitable solvent such as methanol, ethanol, water or mixtures thereof using a suitable base such as hydroxide, carbonate or acetate.

[0240] The compound of formula III can be activated as follows: i) forming an acid chloride from the acid using a suitable reagent such as oxalyl chloride or thionyl chloride; ii) treatment with a reagent such as an alkyl chloroformate to form an anhydride or mixed anhydride; iii) activation of the acid in the amide coupling reaction using conventional methods, for example, EDCI with HOBt or a urea cation salt such as HBTU; iv) formation of alkyl esters upon deprotonation of hydroxyamidines using a strong base such as t-butanol; v) any other suitable activation method to form the desired substrate.

[0241] Ester formation can be achieved using a suitable aprotic solvent such as dichloromethane, tetrahydrofuran, N-dimethylformamide or toluene, optionally with a suitable organic base such as triethylamine, diisopropylethylamine or the like or an inorganic base such as sodium bicarbonate or potassium carbonate.

[0242] The cyclization of the ester to form the oxadiazole can be carried out by evaporation and substitution of the crude ester with a solvent having a higher boiling point, such as DMF, or by extraction with water to provide a semi-purified starting material, or a starting material purified by standard chromatographic methods. The cyclisation may be effected by conventional heating or microwave irradiation (100-.

[0243] Other compatible non-reactive functional groups suitable for protection may also be present in the substrate.

[0244] Further examples of such reactions are presented in Poulan et al, Tetrahedron Lett., (2001), 42, 1495-98, Ganglott et al, Tetrahedron Lett., (2001), 42, 1441-43, which are incorporated herein by reference.

[0245] Synthesis of nitriles and acids for the preparation of Compounds of formulae II and III

[0246]Aryl nitriles can be obtained by a variety of methods including cyanation of aryl halides or trifluorformates in a suitable solvent such as N, N-dimethylformamide, using a suitable cyanide source such as zinc cyanide, under palladium or nickel catalysis. The corresponding acid can be obtained by hydrolysis of the nitrile in a suitable solvent, such as aqueous ethanol, under acidic or basic conditions. Aryl acids can also be obtained from a variety of other sources, including iodine-or bromine-lithium exchange, followed by CO capture₂Directly obtain the acid.

[0247] The acid can be converted to the primary amide using any compatible method of activating the acid, including via an acid chloride or mixed anhydride, followed by capture with ammonia from any source, including ammonium chloride, ammonium hydroxide, ammonia in methanol in the presence of a suitable base, or ammonia in an aprotic solvent such as dioxane. The amide intermediate can be converted to the nitrile using a variety of dehydration reagents such as oxalyl chloride or thionyl chloride. This sequential conversion of the acid to the nitrile may also be applied to non-aromatic acids, including appropriately protected amino acid derivatives. Suitable protecting groups for amines in amino acids or at remote locations of any other acid starting material may be any group that is basic and nucleophilic to remove amine functionality, including carbamate protecting groups such as boc.

[0248] Certain acids are more readily prepared using commercially available analogs. For example, 6-methylpyridine-4-carboxylic acid is produced by dechlorination of 2-chloro-6-methylpyridine-4-carboxylic acid. Specific types of substituted fluoro-benzonitriles and benzoic acids are obtainable from: the temperature is raised (80-120 ℃) in a compatible solvent such as N, N-dimethylformamide in the presence of a base such as potassium carbonate for a sufficient period of time by replacing one fluoro group of bromo-difluorobenzene with a suitable nucleophile such as imidazole. The bromo group can then be made into the acid or nitrile described above.

[0249] 1, 3-disubstituted and 1, 3, 5-trisubstituted benzoic acids and benzonitriles can be prepared using readily available substituted isophthalic acid derivatives. The mono-hydrolysis of the dibasic acid ester allows the selective reaction of the acid with a variety of reagents, most commonly activating agents such as thionyl chloride, oxalyl chloride or isobutyl chloroformate, among others. Many products are available from activated acids. In addition to the formation of nitriles by dehydration as described above, the reduction to the hydroxymethyl analog can be achieved depending on the mixed anhydride or acid chloride in a compatible solvent such as tetrahydrofuran, using a variety of reducing agents such as sodium borohydride. The hydroxymethyl derivative may be further reduced to the methyl analogue by catalytic hydrogenation with fluorine in a suitable solvent such as ethanol using a suitable catalyst source such as palladium on carbon. Hydroxymethyl can also be used in any reaction suitable for benzyl alcohol (benzylic alcohols) such as acylation, alkylation, conversion to halogen, and the like. Halomethylbenzoic acids of this type can also be prepared by bromination of methyl derivatives, when they are not commercially available. The ethers obtained by alkylation of hydroxymethyl derivatives can also be derived from: halomethylarylbenzoate derivatives are reacted with the appropriate alcohol in an appropriate solvent such as tetrahydrofuran or ethanol using an appropriate base such as potassium carbonate or sodium hydroxide. These may also be applied to standard conversion reactions when other substituents are present. Treatment of aniline with acid and sodium nitrite can produce a diazonium salt which can be converted to a halide such as fluoride using tetrafluoroboric acid. Phenols are reacted with alkylating agents in the presence of a suitable base such as potassium carbonate to form aromatic ethers.

[0250] Formation of Compounds of formula IX

[0251]A compound of formula IX, wherein R⁷Independently selected from M¹-(R²)_n-P-(R¹)_m1、M²-(R³)_n-X⁴-Q-(R⁴)_m2And M²-(R³)_n-G, wherein G is a leaving group or a group which can subsequently be converted into a leaving group. The compound of formula IX may be prepared by 1, 3-dipolar cycloaddition between compounds of formula VI and VII in a solvent such as toluene at a suitable temperature (0 ℃ to 100 ℃) and basic conditions using a suitable base such as sodium bicarbonate or triethylamine. The synthesis of compounds of type VI has been described in the literature, for example Kim, Jae Nyouung; ryu, yang K; chem. (1992), 57, 6649-50. 1, 3-dipolar cycloaddition of alkynes of the type VII can also be caused by using substituted nitromethanes of the type VIII activated via electrophiles, such as PhNCO, in the presence of bases, such as triethylamine, at elevated temperatures (50C-100 ℃ C.). Li, C-S.; lacase, e.; tetrahedron Lett. (2002) 43; 3565-3568. Some compounds of type VII are commercially available or can be synthesized by standard methods known to those skilled in the art.

[0252] Optionally, the compound of formula X is obtained by claisen condensation of methyl ketones and esters in the presence of a base, e.g. using sodium hydride or potassium tert-butoxide, and the compound of formula IX can be formed, e.g. as its hydrochloride salt, at elevated temperature (60-120C) via condensation and subsequent cyclization with hydroxylamine.

[0253] It will be appreciated that subsequent conversion of the functional groups may be necessary for both methods. As for the ester groups, these transformations may include, but are not limited to, any of the following 3 protocols: a) complete reduction in a solvent such as THF using a suitable reducing agent such as LAH. b) Partial reduction using a suitable selective reducing agent such as DIBAL followed by alkylhaloalkylation. c) Alkylation with an alkylmetal reagent such as an alkylmagnesium halide in a solvent such as toluene or THF, followed by reduction with, for example, sodium borohydride in methanol.

[0254] Formation of Compounds of formula XIV

[0255]A compound of the formula XIV, wherein R⁷Independently selected from M¹-(R²)_n-P-(R¹)_m1、M²-(R³)_n-X⁴-Q-(R⁴)_m2And M²-(R³)_n-G, wherein G is a leaving group or a group which can subsequently be converted into a leaving group. Compounds of formula XIV can be prepared by acylation of tetrazole compounds of formula XI with compounds of formula III which can be isolated using a compound of formula III, for example an acid chloride or anhydride, or a compound of formula III which can be formed in situ by LG (for example from activation of an acid using a reagent such as DCC or EDCI), followed by rearrangement to form a 1, 3, 4-oxadiazole. Jursic, b.s.; zdravkovski, z.; Commun.Synth; (1994) 24; 1575-1582.

[0256] Optionally, compounds of formula XIV can also be prepared from hydrazides of formula XII, wherein LG is a leaving group such as chloride or alkoxide, in the presence of a compound of formula XII or III and heating at a temperature of (60-130 ℃). The reaction of the compound of formula XIII can be accomplished either succinctly or easily using a suitable aprotic solvent such as benzene or xylene, or a protic solvent such as ethanol or n-butanol, in the presence of a base such as KotBu or an acid such as p-toluenesulfonic acid or acetic acid. See: saunders, j.; cassidy, m.; freedman, s.b.; harley, e.a.; iversen, l.l.j.med.chem.; (1990) 33; 1128-1138; peet, n.p.; sunder, s.j.heterocyclic.chem.; (1984) 21; 1807-1816. As for the compounds of formula III, dehydrating agents such as phosphorus pentoxide are used to increase cyclization of intermediates of the formation reaction, as previously described, e.g., Kakefuda, Akio; etc.; mede chem. (2002), 10; 1905-1912.

[0257] Formation of Compounds of formula XVI

[0258]A compound of formula XVI wherein R⁸Independently selected from M as defined above¹-(R²)_n-P-(R¹)_m1、M²(R³)_n-X⁴-Q-(R⁴)_m2And M²-(R³)_n-G, wherein G is a leaving group or a group which can subsequently be converted into a leaving group. According to Lee and Hong; tetrahedron lett., (1997), 38, 8959-60, in the presence of in situ generated T1(OTf)₃And reacting the compounds of formulae XVa and XVb under acidic conditions to give the compound of formula XVI.

[0259]Optionally, the compounds of formula III and XVII are reacted as described above for formula V to provide an intermediate product of formula XVIII. Such intermediates are cyclodehydrated to produce oxazolines, followed by use of BrCCl in the same reactor₃Dehydrogenation can yield the desired oxazole. Phillips, aj.; uto, Y; wipf, p.; reno, MJ. and Williams, d.r., Organic Letters, (2000)2, 1165-8.

[0260]By nucleophilic displacement of a leaving group at X⁴And M²Or Q and M²Formation of the bond between:

[0261]compounds of formula XX may be used to displace compounds of formula XIX (R)⁷Is M¹-(R²)_n-P-(R¹)_m1) The leaving group LG of (1). When X is present⁴Represents a heteroatom such as N and S, in the presence of a suitable base such as potassium carbonate, cesium carbonate, sodium hydride, triethylamine, etc.; the base can be prepared by reacting X⁴Deprotonation of the group and prevention of excess acid which would be generated by the reaction in the absence of base facilitates the reaction. The reaction can be accomplished using any suitable solvent, such as acetonitrile or DMF; the reaction can be completed at room temperature or at an elevated temperature (35-100 ℃) which accelerates the reaction.

[0262] Such conditions may be used with appropriate modifications of the apparatus used in the parallel synthesis using standard techniques known to those skilled in the art.

[0263]When X is present⁴Where the bond and ring Q are fused bicyclic rings and contain a heteroatom as defined above, for example N, these reaction conditions are likewise applicable to compounds of formula XX. In the latter or above case X⁴Among N, NaH in DMF is preferred, as described in previous literature, e.g. Murdoch, Robert; tally, w.roger; westwood, Robert; chem. j.heterocyclic; (1986) 23, 23; 833-841.

[0264]As to the compounds containing X⁴Compounds of formula XX as ═ C, it is necessary to use stronger bases such as LDA, n-butyllithium or any other metal alkyl base, in suitable aprotic solvents such as THF, hexane or toluene and at temperatures typically below ambient temperature, for example at-78 ℃ or 0 ℃ to achieve deprotonation.

[0265] An optional step in the synthesis of thiomethyl oxadiazoles of the type described above is by combining the appropriately substituted hydroxyamidine and the appropriately substituted coupling partner of the hexaactivating acid to form the acyclic esters IVa and IVb. The displacement of the chloride using a sulfhydryl nucleophile can occur immediately prior to cyclization using one of the oxadiazole formation methods described above. Substitution can also be effected for the starting materials of chloromethyl hydroxyamidine or chloromethyl acid, followed by the two steps of esterification and cyclization as described above. Appropriate adjustments of the apparatus used for the parallel synthesis in standard techniques known to the person skilled in the art can also be used in the above-described procedure.

[0266] Formation of 4-alkyl-triazole thiothiols:

[0267]any suitable acylating agent such as an acid chloride or activated acid or the corresponding acid is reacted with a suitable 4-alkyl-3-thiosemicarbazide under amide coupling conditions as described above in the presence of a base such as a pyridine or a non-nucleophilic amine to form the non-cyclic intermediate compound of formula XXV, wherein R is⁴As defined above. The same intermediates can also be obtained by reacting a hydrazide with an alkyl isothiocyanate. Cyclization of the compound of formula XXVI occurs readily and efficiently upon treatment with a suitable inorganic base such as a hydroxide or bicarbonate in a suitable solvent such as water, aqueous dioxane, aqueous alcohol or mixtures thereof at elevated temperature.

[0268] When a solid base is used instead of the above base, the above procedure may be suitably adapted to the apparatus used, for example, P-BEMP using a parallel synthesis method known to those skilled in the art.

[0269] The compound of formula XXV, in its tautomeric form, is reacted with formula XIX under the conditions described above to give the S-alkylated compound of formula Ia.

[0270] Similar procedures can be used to alkylate the other nitrogen atoms on the triazolethiones XXIX and XXXI rings (1 and 2). 2-alkyltriazolethiones XXVIII can be obtained by treatment of aroyl isothiocyanates with alkylhydrazines in toluene at elevated temperatures, e.g. 85 deg.C, followed by heating with aqueous bicarbonate solution. The same product can also be obtained by treating an analogous 2-alkyl-3-thiosemicarbazide with an activating acid in the presence of a suitable base such as pyridine or triethylamine followed by base ring closure in a similar manner to that which gives product XXVI above.

[0271] 1-alkyltriazolethiones XXXI may also be prepared from the reaction of an appropriate N-alkyl-N-hydrazide with potassium thiocyanate in the presence of an acid such as HCl or other compatible strong acid via a 1-acyl-1-alkyl-3-thiosemicarbazide intermediate that undergoes base ring closure in a similar manner to that which produces the compound of formula XXVI above.

[0272] Formation of Compounds of formula XXXIII

[0273]The compounds of formula XXXIII can be prepared by the following steps: alkylation of cyclic thioureas XXXIIa (where n ═ 0, 1, or 2) yields compounds of formula xxxiiib, for example 2-methylthio-1, 4, 5, 6-tetrahydropyrimidine (n ═ 1). Using, for example, methyl iodide as alkylating agent, it is possible to work at room temperature or at elevated temperature with some solvents (DMF, acetone, CH)₂Cl₂Etc.) to obtain the product of hydroiodide; this is as previously described: kennedy, Kevin j.; simandan, Tiberiu L; dix, Thomas a.; Commun.Synth; (1998) (ii) a 24; 741-746. Cyclic thioureas are readily available by synthetic methods known to those skilled in the art or from commercial sources. Hydrazinolysis of a compound corresponding to type XXXIIib gives a compound of formula XXXIIic. Preferably, the hydrazinolysis is carried out with hydrazine hydrate under ethanol reflux; this is as previously described: krezel, Izabella; pharmazie; (1994) (ii) a 94, 27-31. Finally, fused triazoles of formula XXXIII can be formed by heated acylation and condensation reactions between compounds of formula XXI and compounds of formula xxxiiic containing LG as a leaving group, for example halogen. Such reactions can be carried out in pyridine or in ethanol or toluene in the presence of a base. Ordinary heating or microwave irradiation methods may be used. Similarly, XXXIII can be prepared in a suitable solvent such as methanol or ethanol at elevated temperature in the presence of a base such as sodium methoxide, where XXI can also be an ester or carboxylic acid.

[0274]Non-cyclic thioureas of the formula XXXIIid, in which R⁸Is defined in the flow chart,R³And R⁴The definition of (a) is stated in formula I, using a similar method, a compound of formula XXXIIIa is obtained, wherein the introduction of the hydrazine moiety can be carried out by using hydrazine followed by acylation, or by using the hydrazide already formed.

[0275] Formation of Compounds of formula XXXV

[0276] Preparation of compounds of formula XXXIVb the compounds of formula XXXIVb can be prepared using a similar method to that described above, for example by activating XXXIVa to give the corresponding imidoyl chloride, optionally in the presence of a base such as triethylamine, using oxalyl chloride or pentachlorophosphosphosphosphonium. As used above, the intermediate may be isolated for use in situ or before capture by a compound of formula XXIII. The subsequent product may be cyclized in a suitable solvent such as DMF under acidic or basic conditions to give the compound of formula XXXV. XXXV may be an intermediate used to form the compound of formula I, or may be the final biologically active compound of formula I.

[0277]Compounds of formula XXXV, R of which R is an ester of formula XXXVIa (the imino ethyl esters described as examples) may also be prepared by reaction with a compound of formula XXXVIb followed by cyclisation at elevated temperature in the presence of an amine⁸Independently selected from the group as described above; however, the amine is preferably, but not limited to, one having a low boiling point, for example, one which can be used in excess and which simplifies the operation steps. Such amines may be, for example, but are not limited to, methylamine or ethylamine used as a solution in, for example, methanol, THF or dichloromethane.

[0278] Formation of Compounds of formulae XXXVIa and XXXVIb

[0279]The formula XX can be prepared by reaction of a nitrile of formula XXXVie in the presence of a protic acid such as hydrochloric acid in an alcohol such as ethanolXVIa compounds, wherein R⁸Independently selected from the groups described above. Nitriles can be obtained from XXXVId acids as described above. Compounds of formula XXXVId, wherein R8 is independently selected from the group described above, may also be used to prepare hydrazides of formula XXXVIb. XXXVIb may also be formed directly from the acid. It may be advantageous to react an intermediate ester of type XXXVIf with pure hydrazine, a hydrazine salt in the presence of a base or with hydrazine hydrate, which is easier to handle. However, the direct route via acid activation in situ may be advantageous in that the substrate is susceptible to nucleophilic attack, also yielding a product in a shorter number of steps.

[0280] Formation of Compounds of formulae XXXVid and XXXVif

[0281]Wherein R is⁷Is M¹-(R²)_n-P-(R¹)_m1The compounds of formulae XXXVId and XXXVId may be prepared by any one of the non-limiting methods: a) reaction of a hydrazide compound of the formula XII with a cyclic anhydride or a monoesterified diacid, followed by cyclization of the resulting intermediate, respectively (X)¹＝O，X²And X³N) to give 1, 3, 4-oxadiazoles of the types XXXVId and XXXVIf; b) reaction of hydroxyamidines of formula II with cyclic anhydrides or monoesterified diacids and cyclization produces 1, 2, 4-oxadiazole analogs XXXVId or XXXVif, wherein X ¹And X²＝N、X³O; c) reaction of a compound of type III with a hydroxyamidine type compound, with the exception of a succinyl derivative, produces a 1, 2, 4-oxadiazole analog XXXVif, where X is¹And X³＝N、X²O. The compounds XXXVId and XXXVId may be independent of X as described above¹、X²Or X³The kind of the same.

[0282] Formation of Compounds of formula Ib

[0283]Wherein R is⁷Is selected from M¹-(R²)_n-P-(R¹)_m1Preparation of a compound of formula Ib: can be prepared from compounds of formula XXXVII, produced from XIV as described below, via Me₃OBF₄Or dimethyl sulfate selective O-alkylation (as described in the literature, e.g., a) Sheu, Jennline; smith, Michael b.; oeschger, Thomas r.; satchell, Jacqeline; org.prep.procedint; (1992) (ii) a 24, 147-; or b) Hutchinson, Ian S.; matlin, Stephen a.; mete, Antonio, Tetrahedron lett; (2001) (ii) a 42; 1773-1776). The methoxy group can then be replaced by a hydrazide of type XXIII followed by ring closure condensation to form a triazole heterocycle. This can be done in ethanol, toluene, DMF or pyridine under the thermodynamic conditions of the usual heating or microwave irradiation methods, as described before, for example Lawson, Edward C; hoekstra, William j; ado, Michael f.; Andrade-Gordon, Patricia; damiano, brucep.; kauffman, Jack a.; mitchell, John a.; maryanoff, Bruce e.; bioorg.med.chem.lett.; (2001) (ii) a 11; 2619-2622.

[0284] A preferred subgroup of compounds of the formula Ib are those of the formula g and can be prepared according to the following scheme:

[0285]the compound of formula b may be produced by: by using Me₃OBF₄Or dimethyl sulfate selective O-alkylation of cyclic lactams (as described in the literature, e.g.: a) Sheu, Jennline; smith, Michael b.; oeschger, Thomas r.; satchell, Jacqeline; org.prep.proced.int.; (1992) (ii) a 24, 147-; or b) Hutchinson, Ian S.; matlin, Stephen a.; mete, Antonio, Tetrahedron lett; (2001) (ii) a 42; 1773-1776). The methoxy group can then be replaced by hydrazine or hydrazine to form intermediate c, which can be acylated to form intermediate d. Optionally using acyl radicalsHydrazine can displace the methoxy group directly to yield d. The ring-closing condensation to form the triazole heterocycle may be carried out in ethanol, toluene, DMF or pyridine under the thermodynamic conditions of conventional heating or microwave irradiation methods, as previously described, for example Lawson, Edward C; hoekstra, william j.; ado, Michael f.; Andrade-Gordon, Patricia; damiano, Bruce p.; kauffman, Jack a.; mitchell, John a.; maryanoff, Bruce e.; bioorg.med.chem.lett; (2001) (ii) a 11; 2619-2622.

[0286]Wherein R may be prepared by deprotonating and reacting a compound of formula e with a compound of formula f⁷Is selected from M¹-(R²)_n-P-(R¹)_m1A compound of formula (i) g. This reaction can be accomplished using a strong base due to the stability of the aromatic triazole ring, but is facilitated when the R group provides additional stability to the resulting carbanion, for example, as an ester, nitrile, or sulfone.

[0287] Compounds of type XXXVII can be prepared by: sequential treatment in an aprotic solvent such as THF from a cyclic amide, a lactam, which is easily alkylated at the α -position of the carbonyl group, with 2 equivalents of a strong base such as n-Buli yields a divalent anion, followed by addition of 1 equivalent of the compound of formula XIX; this is as described previously, e.g., Grieco, Paul a; kaufman, Michael d.; chem.; (1999) (ii) a 64; 6041-6048). Optionally, N-protected lactams can be used: only 1 equivalent of a base such as LDA is required to generate the anion for alkylation as previously described, e.g., Padwa, Albert; beall, l.scott; heidelbaugh, Todd m.; liu, Bing; sheehan, Scott m.; chem.; (2000) (ii) a 65; 2684-2695.

[0288] General Synthesis of Compounds of formula Ic

[0289]Wherein R may be prepared by reacting the subsequently cyclized compound of formula XXXVIII with a compound of formula XXXIX ⁷Is M¹-(R²)_n-P-(R¹)_m1A compound of formula Ic. Compounds of formula XXXIX can be prepared from the appropriate secondary amide by using oxalyl chloride or phosphorus pentachloride, optionally in the presence of a base such as triethylamine, and used in situ or as starting material for isolation as described in XXXIVa.

[0290] The compounds of formula XXXVIII can be prepared by reaction of the corresponding alcohol with phosgene or preferably a phosgene analogue such as carbonyldiimidazole, followed by coupling with hydrazine.

[0291]Wherein R is⁴Is O and R⁷Is M¹-(R²)_n-P-(R¹)_m1Other synthesis methods for compounds of formula Ic or Id can be O-alkylation of a compound of type XL with XLI of type containing a leaving group in a suitable base such as cesium or potassium carbonate, sodium hydride in a solvent such as DMF or DMSO; the leaving group may be tosyl, mesyl, halogen or any other suitable group.

[0292] Type XLI compounds can be synthesized as exemplified with triazole: the sulfur-containing groups are alkylated or arylated using a suitable alkylating or arylating agent, followed by double oxidation of the thio groups to the corresponding sulfones using an oxidizing agent such as MCPBA in acetic acid, hydrogen peroxide or potassium permanganate. Such an order is previously described, for example Å kerblom et al j. med. chem.16, 312 (1973). Optionally the triazole halide may be synthesised as described in the previous literature, for example Ashton, w.t. et al j.med.chem.36, 591 (1993).

[0293] Alcohols can be prepared as described in the general synthesis of compounds of formula V above, either directly on oxadiazole or on isoxazole. The optional preparation method is as follows: the aldehyde (or hydrate thereof) so synthesized is subjected to a standard reduction scheme from an oxadiazole or isoxazole unit containing a suitable leaving group, e.g. a halide, such as chloride, using a three-step sequence (j.heterocyclic. chem. (1979) 16: 1469) as described by Palazzo, followed by, for example, sodium borohydride in methanol.

[0294] Yet other methods may include: compounds of formula XIV unit containing a suitable leaving group such as a halogen, e.g., chlorine, are reacted with hydroxybenzotriazole in a suitable solvent such as DMSO, acetonitrile, acetone in the presence of a suitable base such as potassium carbonate or triethylamine to give compounds of type XLa. XLa can optionally be obtained: during the cyclization to oxadiazole, the hydroxybenzotriazole, if present, either together with EDCI as co-activator or as by-product from a coupling reagent as described above, such as HBTU, can be converted to an alcohol by adding samarium diiodide, preferably over an extended period of time (5-360 min), using the preferred solvent THF at the appropriate temperature (-75 ℃ to +75 ℃), under reaction of compounds of formulae II to V.XLa in a suitable solvent such as tetrahydrofuran, methanol, water or mixtures thereof.

[0295] Cleavage of the N-O bond is optionally performed as follows: conventional hydrogenation processes are employed in the presence of suitable catalysts, such as raney-nickel catalysts known to those skilled in the art. In the compound of formula XLa, oxybenzotriazole functionality may also be used as a leaving group. Thus, compound XLa can be reacted with compound XX, as described above.

[0296] Formation of Compounds of type Ie

[0297]Wherein R is⁷Is M¹-(R²)_n-P-(R¹)_m1The compounds of formula Ie can be prepared by nucleophilic substitution of a compound of type XLIIIb with a compound of type XIX as described above. Under heatingUsing P₂S₁₀Or Lawesson's reagent, compounds of type XLIIb can be prepared by reaction to their oxo-analogue XLIIa. The synthesis of compounds of type XLIIIa is described in Takeuchi, h., Hagiwara, s., Eguchi, s., Tetrahedron (1989); 45, a first step of; 6375-6386.

[0298] Introduction of Q Ring substitution:

[0299]if substitution on the Q ring is desired, an appropriate choice of substituted aryl or heteroaryl thiols can be used for the metathesis reaction. Other nucleophiles are equally effective, except for the same substituted or unsubstituted aryl or heteroaryl thiols used to replace them in the final compound. If the aryl or heteroaryl residue has a reactive moiety that can be affected, it is either introduced directly or as a result of deprotection includes, but is not limited to, free NH positions such as in aniline, imidazole, benzimidazole, indole, etc.; r can be used to deprotonate the NH group using a suitable base such as an alkyl lithium or alkali-metal hydride or hydroxide, followed by the addition of a suitable electrophile such as a halocarbon, acid chloride or anhydride, chloroformate, carbamoyl chloride, sulfonyl chloride, isocyanate, isothiocyanate or the like ⁴Substituted compounds of formula If (R)⁷Is M¹-(R²)_n-P-(R¹)_m1) Providing a substituted product of formula Ia.

[0300]M²Substituent and X⁴Introduction of substituents:

[0301]when the most acidic proton is located adjacent to X⁴On an atom of or at X⁴The compounds of formula Ia are deprotonated as such by using a strong base such as an alkyllithium or alkali-metal hydride in a suitable aprotic non-acidic solvent such as THF or diethyl ether, followed by treatment with a suitable electrophile such as a halocarbon, acid chloride or anhydride, chloroformate, carbamoyl chloride, sulfonyl chloride, isocyanateAnd isothiocyanates, etc., trapping the synthesized anions, and substitution can be accomplished. When an excess of base and electrophile is used and the reaction allowed to proceed for a sufficient time, both hydrogens may be replaced with electrophiles as illustrated below, introducing two R' s³Substituent (M)²An example is carbon). Two or more different or identical substituents may also be introduced by successive deprotonations and reactions with suitable electrophiles to give compounds of the formula Ig.

[0302]In the chain S atom (when X)⁴Is S) or oxidation of the N atom on the substituent:

[0303] oxidation of the sulfur atom can be accomplished by direct oxidation using any suitable oxidizing agent, including peroxy acids such as MCPBA, to give sulfones (Y ═ O) and sulfoxides (Y ═ i ", i.e., unshared electron pairs). With respect to MCPBA oxidation, it is possible to obtain a mixture of products from a single reaction and can be separated by standard column chromatography, or alternatively a sulfoxide or sulfone by controlling the stoichiometry and temperature of the reaction.

[0304]If one substituent is, for example, R⁴Containing one or more nitrogen atoms, e.g. pyridine moieties or any other substituents as defined above, then oxidation of the nitrogen may take place in the above reaction of Ia with an oxidizing agent, e.g. MCPBA, to give the corresponding N-oxide. Those skilled in the art will understand that: such products can be obtained by separation by standard column chromatography or any other standard purification scheme, as in the case of mixtures containing, for example, formula Ih and N-oxides. Those skilled in the art will also appreciate that: by selecting suitable reaction conditions, e.g. using acidic media for the protection of basic amines, the N-oxide content can be reducedAnd (4) forming.

[0305] Other multifaceted reactions:

[0306]where the intermediate compound contains a suitable reactive functionality, such as an aryl halide or triflate, the functionality may be further applied to prepare the product. For example, when 3-halo-phenyl is present in P- (R)¹)_m1In (1), standard Suzuki conditions may be used to couple the aryl boronic acid to form the diaryl coupling product. Miyaura, n., Yanagi, t., Suztki, a., synth. commun., (1981), 11, 7, 513-.

[0307] Other functionalities such as aliphatic alcohols can be converted to fluorine groups, for example, by using fluorinating agents such as DAST, or converted to other halogen compounds by using, for example, triphenylphosphine and either iodine, N-bromosuccinimide or N-chlorosuccinimide. These halogen compounds may be used as leaving groups for further processing or may remain as substituents for the active compounds of formula Ia.

[0308] Alcohols in a similar fashion can be converted to leaving groups such as the non-limiting examples methanesulfonyl or toluenesulfonyl in the presence of a non-nucleophilic base by the use of an appropriate sulfonyl halide or sulfonyl anhydride to give the sulfonate derivative.

[0309]Other functionalities which can be further processed are described in the following, non-limiting examples (R)⁷Is M¹-(R²)_n-P-(R¹)_m1) Where chlorinating agents such as sulfuryl chloride are used, the carbon atoms of the oxazole can be halogenated.

[0310] Additional reactions for preparing intermediate and final compounds

[0311] In the following synthetic schemes and corresponding descriptions, further specific reaction types for the preparation of the compounds of the formula I and the intermediates thereof, where applicable, are given. Unless otherwise indicated, the definitions in the following formulae are as described in the formulae. Other starting materials are commercially available or can be prepared by methods described in the literature.

[0312]Intermediate compound

[0313] Alkylsulfonyl [1, 2, 4] triazoles

[0314]Referring to scheme 1, corresponding [1, 2, 4] is reacted at-30 to 100 ℃]Triazolethiones in MeOH, EtOH, THF, acetone, or the like, initial alkylation of the sulfur atom with primary alkyl halides such as MeI and EtI (alkyl groups are Me and Et, respectively), followed by subsequent alkylation at-20-120 deg.C in water and acetic acid mixtures, or mCPBA in DCM using, for example, KMnO ₄Alternatively, the alkylsulfonyl [1, 2, 4] can be prepared by oxidizing the sulfur atom with another suitable oxidizing agent]A triazole. Preparation of [1, 2, 4] by N-acylation of, for example, thiosemicarbazide]Triazolethiones: n-acylating the thiosemicarbazide with any suitable acylating agent, such as an acid chloride (LG is Cl) in, for example, pyridine or an acid (LG is OH) that can be activated by standard activating reagents as described below in DMF, THF, DCM, or the like at-20-120 ℃; subsequently either spontaneously under acylation conditions, or in pyridine or in an aqueous solvent, in a base such as NaHCO₃Or Na₂CO₃The initially formed acyclic intermediate is ring-closed by heating at 50-150 ℃ in the presence or absence of a co-solvent such as dioxane, THF, MeOH, EtOH or DMF. Acyclic intermediates can also be formed by treatment of the appropriate isothiocyanate with the appropriate hydrazide at-20 to 120 ℃ in, for example, 2-propanol, DCM, or THF.

[0315] Amino [1, 2, 4] triazoles

[0316] Referring to scheme 2, the amino [1, 2, 4] triazole is obtained by treating a carbohydrazone diamide with a suitable acylating agent bearing a leaving group LG in a suitable solvent such as THF, pyridine or DMF at-20-100C. The reaction initially produces a ring-opened intermediate which subsequently forms either a triazole ring spontaneously or by heating at 50-200 ℃ in, for example, pyridine or DMF. The leaving group LG may be chloro or any other suitable leaving group such as, for example, a leaving group produced by treatment with a standard activating reagent as described below in situ of the corresponding acid (LG is OH). The carbohydrazone diamide can be generated from isothiourea, where the S-alkyl (e.g., S-Me or S-Et) moiety in the isothiourea acts as a leaving group when treated together with hydrazine in a solvent such as pyridine, methanol, ethanol, 2-propanol or THF at-20-180C. The isothiourea can also be treated with the hydrazide under the same conditions as described for the hydrazine reaction to directly form a ring-opened intermediate. Isothiourea is obtained by S-alkylation of the corresponding thiourea with, for example, MeI or EtI in acetone EtOH, THF, DCM, or the like at-100 to 100C.

[0317] Carbon-substituted [1, 2, 4] triazoles

Scheme 3

[0318]Referring to scheme 3, imidoyl chloride is reacted with hydrazide in a suitable solvent such as THF, pyridine or DMF at-20-100 deg.C to initially form a ring-opened intermediate, followed by the subsequent, or spontaneous, formation of the triazole ring, or in, for example, pyridine, DMF or water, with or without a base such as NaHCO₃Or Na₂CO₃Forming a triazole ring by heating at 50 to 200 ℃ in the presence of the solvent. The imidoyl chloride ammonia can be obtained by standard methods such as treatment of the corresponding amide sequentially with oxalyl chloride or thionyl chloride.

[0319] Imidazole-4-aldehydes and [1, 2, 4] triazolic aldehydes

Scheme 4

[0320]Referring to scheme 4, imidazole-4-aldehyde (X) is prepared by reaction of a suitably substituted amidine with 2-bromo-3-isopropoxyacrolein in, for example, a well-stirred organic solvent such as chloroform, DCM, or a mixture of toluene and water at 10-100 deg.C in the presence of a base such as a carbonate⁵Is C). Using standard methods, the urethanene (alkyl is e.g. Me or Et) is formed from the corresponding nitrile by treatment with e.g. hydrochloric acid solution in the corresponding alcohol solvent, followed by R⁵The raw material amidine can be prepared by the treatment of the amine with the substituent group; or directly from the corresponding nitrile together with the same ammonia and trimethylaluminum. By using e.g. MnO ₂And other standard oxidizing agents for this type of conversion, by oxidation of the corresponding primary alcohols, to produce [1, 2, 4]]Triazolic aldehyde (X)⁵Is N). In turn, these alcohols can be prepared by the hydroxymethylation of the corresponding C unsubstituted triazole using, for example, formaldehyde (formaline) at elevated temperature. For example by [1, 2, 4]]Standard desulfation of triazolethione with Raney's nickel produces C unsubstituted triazole.

[0321] Isoxazole-5-carboxylic acid esters

Scheme 5

[0322] Referring to scheme 5, isoxazole is formed using a dioxybutyrate derivative reacted with hydroxylamine hydrochloride in a solvent such as ethanol, 2-propanol or DMF at a temperature of 40-140 ℃ with in situ cyclization. The dioxybutyrate derivatives are formed by reacting acetophenone with a dialkyl oxalate (alkyl is e.g. Me or Et) in a solvent such as DMF or toluene at a temperature of-20 to 120 ℃ in the presence of a strong base such as sodium hydride.

[0323] Carbon-substituted [1, 2, 4] oxadiazoles

[0324]Referring to scheme 6, G is prepared by dissolving G in a solvent such as pyridine, DMF or water containing a mixture thereof, alternatively at a temperature of 40-140C in an aqueous alcoholic solvent in the presence of sodium acetate at a temperature of 40-140C¹-and G²Cyclisation of substituted acyloxyimino amides (acyloxyimino amides) to form G ¹、G²And G³[1, 2, 4] as defined in scheme 6 and having carbon α attached to the heterocycle]An oxadiazole; if G is¹Or G²One containing a chiral stereocenter, preferably the latter method. By reaction of a suitable acylating agent bearing a leaving group LG with G¹Coupling of the substituted hydroxyamidine intermediates to form acyloxyiminoamides. The leaving group LG may be chloro or other suitable leaving group such as, for example, one produced by treatment with a standard activating reagent as described herein below in situ with the corresponding acid (LG is OH). Reacting the corresponding nitrile with hydroxylamine free base or hydroxylamine hydrochloride in a solvent such as ethanol, water or pyridine at a temperature of-20 to 120 ℃ in the presence of a base such as triethylamine, pyridine or sodium carbonate to form G¹-substituted hydroxyamidines.

[0325] Amino [1, 2, 4] oxadiazoles

Scheme 7

[0326]Referring to scheme 7, the corresponding bromo [1, 2, 4] is prepared by reaction of the corresponding bromo [1, 2, 4] in a solvent such as methanol or ethanol at elevated temperature]Reaction of oxadiazoles with excess alkylamine to give amino [1, 2, 4]]An oxadiazole. At elevated temperature to dissolveIn an agent such as toluene or DMF in a base such as NaHCO₃In the presence of a benzonitrile derivative, reacting the benzonitrile derivative with a hydroxy carbodiimide dibromide to give the intermediate bromo [1, 2, 4] ]An oxadiazole.

[0327] Carbon-substituted [1, 3, 4] oxadiazoles

[0328] Referring to scheme 8, starting from the coupling of a hydrazide with an aliphatic acid chloride derivative in THF, DMF, or toluene, or the like, optionally in the presence of a base such as triethylamine or carbonate, resulting in the formation of an acylbenzoyl hydrazine derivative, the acylbenzoyl hydrazine derivative is cyclized at elevated temperature in a solvent such as toluene or DMF or mixtures thereof in the presence of a dehydrating agent such as phosphorous pentoxide to yield the [1, 3, 4] oxadiazole product. Optionally, the [1, 3, 4] oxadiazoles can be prepared directly from hydrazides using trialkyl orthoesters either neat or in a solvent such as toluene or xylene at elevated temperature: .

[0329] Conversion of functional groups

[0330]Referring to scheme 9, aliphatic alcohols can be converted to the corresponding halides, for example, by standard methods using, for example, triphenylphosphine in combination with either iodine, N-bromosuccinimide, or N-chlorosuccinimide, optionally, or treatment with phosphorus tribromide or thionyl chloride. Alcohols in a similar fashion can be converted to other leaving groups such as mesylate or tosylate by the use of the appropriate sulfonyl halide or sulfonyl anhydride in the presence of a non-nucleophilic base to give the corresponding sulfonate. The chloride or sulfonate ester can be converted to the corresponding bromide or iodide by treatment with a bromide salt, such as LiBr, or an iodide salt. More criteria for obtaining alcohol The process comprises reacting a compound containing a group such as methyl or ethyl ester, aldehyde (R) with a conventional reducing agent such as borane, lithium borohydride, lithium aluminum hydride, or hydrogen in the presence of a transition metal catalyst such as a ruthenium or iridium complex, or optionally palladium on carbon³Is H) or a ketone (R)³The corresponding carbonyl group other than H).

[0331] Stereoselective preparation of chiral secondary alcohols

Scheme 10

[0332]Kinetic resolution of racemic or optically active (scalemic) secondary alcohols is achieved by enzymatic acetylation using, for example, polymer-bound Candida Lipase (Novozyme 435 (R)) or other esterases such as Candida rugosa or Pseudomonas fluorescens, using an acetylating agent such as vinyl acetate, other substituted alkyl acetates, pentafluorophenyl acetate or nitro-or halophenyl acetates in an organic solvent such as toluene, t-butyl methyl ether, t-butanol or DCM at a temperature of 0-90 deg.C, as in scheme 10 (R) (scheme 10) (R)³Is Me or Et), which yields enriched (R) -acetate and enriched (S) -alcohol. Hydrolysis of (R) -acetate to the corresponding alcohol in a mixture of THF and water by using, for example, lithium hydroxide or by other methods as described below produces the opposite enantiomerically enriched or purified alcohol.

Scheme 11

[0334]At a temperature of 0 to 150 ℃ in a solvent such as MeOH or EtOH⁴Replacement of the leaving group LG by a substituted amine (LG is for example Cl, Br or OMs)) The isothiourea described in scheme 11 can be obtained. Adding the product to R in a solvent such as chloroform, ethanol, methanol or DMF at a temperature of-20 to 100 deg.C⁵In a substituted isocyanate, a thiourea intermediate is produced; the thiourea intermediate may be alkylated by an alkylating agent such as methyl-or ethyl iodide or other suitable alkyl halo-or sulfonate ester in a solvent such as methanol, ethanol, acetonitrile or acetone, in the presence or absence of a base such as triethylamine or potassium carbonate.

[0335] Propionic acid derivatives

[0336]Propionic acid derivatives such as saturated alkyl esters, saturated free carboxylic acids or saturated hydrazides can be prepared as described in scheme 12. The carboxylic acid is obtained, for example, by hydrolysis of the corresponding ester in methanol under basic conditions such as sodium hydroxide, or by any other method known to those skilled in the art. In turn, the corresponding saturated alkyl esters can be obtained from unsaturated esters by reducing the carbon-carbon double bond with hydrogen in the presence of a metal catalyst, such as palladium on carbon, at atmospheric or elevated pressures up to 100 bars; or any other selective reducing agent for this type of compound as known to the person skilled in the art may be used. In the preceding hydrogenation, the removal of the aromatic radical R by hydrogenation-dehalogenation ⁶Any halogen substituent of (a). Unsaturated esters can in turn be obtained by an ene-forming reaction, for example of the Wittig or Homer-Wadsworth-Emmons type, by reaction of an aldehyde or ketone with an appropriately substituted phosphonium ylide or phosphate ester, for example triethyl-2-phosphinopropionate or ethyl 2- (diethoxy-phosphoryl) -propionate, in a suitable solvent, for example acetonitrile or THF, in the presence of a suitable base, for example n-BuLi or DBU, at a temperature of-90 to 100 ℃. Hydrazides can be obtained by reaction of hydrazine with the corresponding ester or by activating the free carboxylic acid by the method described herein below and coupling with hydrazine.

[0337]Preparation of the Final Compounds

[0338] Some non-limiting methods of preparing the final compounds are illustrated and exemplified by the drawings in the general groups or other structural elements of those intermediates corresponding to formula I. It can be understood that: intermediates containing any other general groups or structural elements than those of formula I can be used in the exemplified reactions, as would be known to those skilled in the art, provided that such groups or elements do not interfere with the reaction and can be chemically converted to the corresponding groups or elements of formula I at a later stage.

[0339]Attachment to nucleophilic X ⁴

[0340]Reference is made to scheme 13 wherein X⁴Acting as a nucleophilic group, the formation of a bond by nucleophilic substitution of the Leaving Group (LG) can produce compounds of formula I. In its anionic form X⁴Can be carbon or nitrogen atom, by reacting the corresponding protonated neutral atom with a base in a suitable solvent, e.g. LDA or nBuLi in THF, diethyl ether or toluene, e.g. NaH in DMF, acetonitrile or a ketone, e.g. K in 2-butanone at a temperature of-100 to 150 ℃₂CO₃Processed together to produce. When X is present⁴Is carbon, LG is preferably bromo; when X is present⁴Is nitrogen, examples of suitable leaving groups LG are chloro, bromo, Oms and Ots. When X is present⁴Is N, by using enantiomerically purified or enriched starting materials in which the leaving group LG is attached to the stereocenter, it is also possible to carry out the reaction in a stereoselective manner. Optionally, an alkali metal iodide, such as a catalytic or stoichiometric amount of LiI, may be present in the reaction, which facilitates the reaction by displacing the leaving group in situ to iodine.

[0341] Attachment to nucleophilic oxygen

[0342]Referring to scheme 14, the reaction is facilitated. The compounds of formula I can be prepared under basic conditions by nucleophilic substitution of the Leaving Group (LG) to form a bond, wherein the alcohol acts as an O-nucleophilic group. As the base, use is made of, for example, NaH or Cs ₂CO₃In polar aprotic solvents such as DMF or acetonitrile at temperatures of 0 to 100 ℃ it is preferred to use Cs for obtaining enantiomerically pure products₂CO₃. Examples of suitable leaving groups are sulfonates such as OMs and halogens such as chlorine.

[0343] Related alpha-alkylation of ring Q

[0344]Referring to scheme 15, without R³Group-substituted compounds of formula I can be attached either mono-or dialkylated in the alpha position of ring Q. The dialkylation can be carried out successively on two different or identical radicals R³The introduction of (1). Preferably, a haloprimary alkane, mesyl ester, or tosylate is used as the alkylating agent (R) in the nucleophilic reaction with an intermediate carbanion³-LG); wherein the intermediate is produced by treating with zero or one R with a strong base such as NaH, LDA or HMDS alkali metal salt in a solvent such as THF, diethyl ether, hexane or toluene at a temperature of-100 to 50 deg.C³Group-substituted compounds of formula I.

[0345] Formation of triazole rings

[0346]Referring to scheme 16, a leaving group LG is carried in a solvent such as pyridine, methanol, ethanol, 2-propanol, or THF at-20 to 180 deg.C¹For example, an intermediate such as SMe or Set can be reacted with hydrazine. Followed byUsing LG bearing a leaving group in a suitable solvent such as THF, pyridine or DMF at 0-100 deg.C ²The acylating agent(s) to produce a ring-opened intermediate which either spontaneously forms a triazole ring or is forced to ring-close by heating at 50-200 ℃ to finally form the compound of formula I. LG (Ligno-lead-acid)²May be chloro or other suitable leaving group, the leaving group being generated, for example: in situ reacting the corresponding acid (LG) in a suitable solvent such as DMF, DCM, THF or acetonitrile at a temperature of 20-100 deg.C in the presence or absence of a co-reagent such as HOBt or DMAP²Is OH) is treated with a standard activating reagent such as DCC, DIC, EDCl or HBTU. Optionally, the hydrazide can be reacted with LG bearing a leaving group under the conditions described above for the production of compounds of formula I¹The intermediate (2) is directly reacted.

[0347] Formation of Ring Q

Scheme 17

[0348]Referring to scheme 17, ring Q of compounds of formula I can be formed by reaction of an ester (G is, e.g., OMe or OEt) or an activated acid derivative, e.g., an acid chloride (G is Cl) or other corresponding acid (G is OH) as obtained by treatment with a standard activating agent as described herein above, with an N-hydroxyamidine. When esters are used, suitable conditions include the use of the solvents 1-propanol, 2-propanol, ethanol or toluene in combination with a stoichiometric amount of a base such as potassium tert-butoxide at 0 to 180 ℃. When an activated acid derivative is used, the reaction can be carried out, for example, in-20 to 120 ℃ DMF, DCM, THF, pyridine, or the like. The initially formed acyclic intermediate can spontaneously ring to form [1, 2, 4 ] ]Oxadiazoles are formed by heating them at 50-200 ℃ in pyridine, DMF, EtOH, MeOH or their aqueous mixtures, with or without additives such as sodium acetate. Adding hydrazide (G is NHNH) in MeOH, EtOH, THF or DMF at 0-150 deg.C₂) With imino esters (alkyl being, for example, Me or Et) or corresponding salts, giving ring Q of [1, 3, 4]Oxadiazole compounds of formula I

[0349] N-alkylation of heterocyclic amines

[0350]Referring to scheme 18, R is attached to a Leaving Group (LG)³The nitrogen atom of the group acts as a nucleophilic group, and the compound of formula I can be prepared by bond formation by nucleophilic substitution of the leaving group. The reaction is facilitated by treatment with a base such as LDA, an alkali metal salt of HMDS or nBuLi in THF, diethyl ether or toluene, or NaH in DMF at a temperature of-100 to 150C to effect deprotonation of the nitrogen atom to produce a stronger nucleophile. Suitable leaving groups include, for example, chlorine, bromine, iodine, OMs or OTs. Useful intermediates carrying leaving groups can be prepared, for example, by halogenation of the corresponding compounds wherein LG is hydrogen. For example, SO may be used in solvents such as DCM and DMF₂Cl₂Treatment to give alpha-chlorotriazole (LG is Cl or X) ⁵Is N).

[0351] Cytochrome P450 mediated dealkylation

[0352]A compound of formula I, wherein X⁴Is nitrogen and R⁴Is an alkyl group, preferably a methyl group, which can be converted to R, wherein R is a group which can be converted by incubation with human liver microsomal protein, or other sources of cytochrome P450 isozymes including preferably the 3A4 isozyme, at 35 to 40 ℃ in the presence of, for example, phosphate buffered aqueous solution, NADPH⁴The corresponding compound being hydrogen.

[0353] Chromatographic separation of enantiomers

[0354]By using, for example, Chiralpak AD^®Or Chiracel OJ^®The enantiomers of the compounds of formula I can be obtained in substantial purity (> 95%) by chromatographic separation of the corresponding racemic or optically active mixtures as the stationary phase and, for example, as the eluent, 2-propanol or ethanol, and a mixture of hexane and ethanol, respectively.

[0355]Examples

[0356] Suitable embodiments of the invention are illustrated by the following non-limiting examples.

[0357] NMR measurements were made on a delta scale.

[0358] The compounds prepared according to examples 1-39 and 100-328 are intermediates.

[0359] The compounds prepared according to examples 40-99 and 329-794 are end products.

[0360]Intermediates

[0361]Example 1

[0362] 6-methylpyridine-4-carboxylic acid

[0363]A balloon filled with hydrogen was attached to a flask containing 2-chloro-6-methylpyridine-4-carboxylic acid (2g, 12.0mmol), 10 wt.% palladium on activated charcoal (0.5g), triethylamine (4.8ml) and ethanol (24ml), followed by stirring at room temperature overnight. The reaction mixture was filtered through celite, washed with methanol and concentrated. The remainder was triturated with dichloromethane and then filtered to give 6-methylpyridine-4-carboxylic acid as a white solid, 1.05g (66%). ¹H NMR(MeOD)δ(ppm)：8.62(d，1H)，7.68(s，1H)，7.60(d，1H)，2.55(s，3H)。

[0364]Example 2

[0365] 1-cyano-3-ethylbenzene

[0366] Argon was bubbled through a solution of 1-bromo-3-ethylbenzene (2.5g, 13.5mmol) in DMF (37ml) for 10 minutes. Zinc cyanide (1.75g, 14.9mmol) and tetrakis (triphenylphosphine) palladium (0) (1.56g, 1.35mmol) were then added. After stirring overnight at 80C, the reaction mixture was diluted with ethyl acetate (35ml) and the precipitate was removed by passing through celite. The filtrate was washed with water (3 ×), saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The product was purified by flash column chromatography using 2% ethyl acetate in hexane to give a colorless liquid (1.42 g). GC-MS (M +): 131.18.

[0367]example 3

[0368] 3-Ethylbenzoic acid

[0369]6M sodium hydroxide (25ml) was added to methanol (25ml) containing 1-cyano-3-ethylbenzene (1g, 7.62mmol), followed by heating at 100 ℃ overnight. After concentrating the reaction mixture, the aqueous layer was washed with dichloromethane (2 ×), and then acidified to pH about 3 with 12M HCl. The precipitate was extracted with ethyl acetate, and then the filtrate was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to give 3-ethylbenzoic acid as a colorless oil, 0.770g (28% yield in 2 steps).¹H NMR(CDCl₃)，δ(ppm)：7.76(d，2H)，7.43(m，2H)，2.67(m，2H)，1.19(t，3H)。

[0370]Example 4

[0371] 3-fluoro-5-methyl-benzoic acid

[0372]Concentrated HCl (30ml) was added to a cooled (-5 ℃) suspension of dimethyl 5-aminoisophthalate (20g, 95.6mmol) in water (75ml) followed by addition of NaNO in portions ₂(7.5g, 109 mmol). The reaction mixture was then stirred for 15 minutes, after which time HBF was added₄(18ml, 100mmol, 48% aqueous solution). The reaction mixture was stirred at 0 ℃ for 30 minutes, and the precipitate formed was collected by filtration and washed with cold methanol (60ml) and diethyl ether (60 ml). The remainder was then decomposed by heating through an oil bath (. about.110 ℃). The cooled mixture was then diluted with ether, concentrated on silica gel and the product was purified by flash chromatography using 5% ethyl acetate in hexane as eluent to give the product as a fluffy white solid 9.0g (44%).¹H NMR(CDCl₃)，δ(ppm)：8.57(s，1H)，7.95(d，2H)，3.97(s，6H)。

[0373] A suspension of dimethyl 5-fluoro-isophthalate (1.7g, 8.0mmol) in methanol (41ml) was treated with 1.0N sodium hydroxide (7.2ml, 7.2 mmol). The reaction was allowed to stir at room temperature overnight. After concentrating the solution, the remaining portion was dissolved with water and transferred to a separatory funnel. The aqueous layer was washed with dichloromethane (3 times) and then acidified to pH2 with 1.0n hcl.

The precipitate was extracted with ethyl acetate, then washed with brine and dried over anhydrous sodium sulfate. After removal of the solvent in vacuo, a total of 1.3g (83%) of 5-fluoro-isophthalic acid monomethyl ester was isolated as a white solid.¹HNMR(DMSO)，δ(ppm)：8.31(t，1H)，7.96(m，2H)，3.91(s，3H)。

[0374]Triethylamine (2.2ml, 16.0mmol) and isobutyl chloroformate (1.0ml, 8.0mmol) were added to an ice-cooled solution containing monomethyl 5-fluoro-isophthalate (1.3g, 6.7mmol) in dichloromethane (20ml) and then warmed to room temperature. After stirring for 2 hours, the reaction mixture was filtered and concentrated. The remaining portion was redissolved with tetrahydrofuran (10ml), followed by dropwise addition of sodium borohydride (1.1g, 29.02mmol) in water (3 ml). After 1 hour, the reaction was quenched with methanol, then diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated. Flash column chromatography on silica gel using 30% ethyl acetate in hexane afforded 3-fluoro-5-hydroxymethyl-benzoic acid methyl ester 667mg (54%) as a colorless oil. ¹HNMR(CDCl₃)，δ(ppm)：7.82(s，1H)，7.63(d，1H)，7.32(d，1H)，4.76(s，2H)，3.93(s，3H)。

[0375]Ethanol (2ml) was added to a round bottom flask containing 3-fluoro-5-hydroxymethyl-benzoic acid methyl ester (667mg, 3.6mmol) and 10 wt.% palladium on activated carbon (300mg) under argon atmosphere. The flask was evacuated using a water pump and then filled with hydrogen gas using a balloon. After stirring for 2 hours, the palladium on carbon was filtered off through celite. The filtrate was then concentrated to give 520mg (87%) of methyl 3-fluoro-5-methyl-benzoate.¹HNMR(CDCl₃)，δ(ppm)：7.65(s，1H)，7.51(d，1H)，7.08(d，1H)，3.91(s，3H)，2.40(s，3H)。

[0376]0.5N lithium hydroxide (7.4ml, 3.7mmol) was added to a solution of 3-fluoro-5-methyl-benzoic acid methyl ester (520mg, 3.1mmol) in tetrahydrofuran (7.4 ml). At 75 deg.CThe reaction was stirred for 2 hours, then the solvent was removed in vacuo. The remaining portion was dissolved with a small amount of water and then acidified (pH about 2) with 10% HCl (aq). The aqueous layer was extracted with ethyl acetate, and then the organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to give 469mg (98%) of 3-fluoro-5-methyl-benzoic acid as a white solid.¹H NMR(DMSO)，δ(ppm)：7.62(s，1H)，7.45(d，1H)，7.32(d，1H)，2.38(s，3H)。

[0377]Example 5

[0378] 3-Methoxymethylbenzoic acid

[0379]A mixture of 3-bromomethyl-benzoic acid methyl ester (556mg, 2.4mmol) and potassium carbonate (670mg, 4.9mmol) in methanol (10ml) was heated with tetrahydrofuran (10ml) at 55 ℃ for 2 h. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. After drying in vacuo, 3-methoxymethyl-benzoic acid methyl ester (436mg, quantitative) ¹H NMR(CDCl₃)，δ(ppm)：8.01(s，1H)，7.98(d，1H)，7.55(d，1H)，7.43(t，1H)，4.50(s，2H)，3.92(s，3H)，3.41(s，3H)。

1N sodium hydroxide (3.6ml, 3.6mmol) was added to 3-methoxymethyl-benzoic acid methyl ester (436mg, 2.4mmol) dissolved in methanol (5ml) and tetrahydrofuran (5 ml). The reaction was stirred at 70 ℃ for 30 minutes, and then the solvent was removed in vacuo. The remaining portion was dissolved with a small amount of water and then acidified (pH about 2) with 1N HCl (aq). The aqueous layer was extracted with ethyl acetate, and then the organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to give 395mg (98%) of 3-methoxymethylbenzoic acid as a white solid.¹H NMR(DMSO)，δ(ppm)：7.90(s，1H)，7.87(d，1H)，7.56(d，1H)，7.48(t，1H)，4.48(s，2H)，3.31(s，3H)。

[0380]Example 6

[00381] N-hydroxy-3-methoxy-benzamidine

[0382] Using Shine et al, j.heterocyclic Chem (1989) 26: 125 general procedure for 128 hydroxylamine hydrochloride (22ml, 5M, 110mmol) and sodium hydroxide (11ml, 10M, 110mmol) were added to a solution of 3-methoxybenzonitrile (11.5ml, 94mmol) in ethanol (130 ml). The reaction mixture was then heated at reflux (80 ℃) for 12 hours. After the mixture was cooled, most of the solvent was removed in vacuo. The crude product was partitioned between ethyl acetate and water, the filtrate was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed in vacuo. Flash chromatography on silica gel using 30-50% ethyl acetate in hexanes afforded the title compound (8.05g, 52%).

Examples 7-9 were prepared in a similar manner to the procedure given in example 6.

[0383]Example 7

[0384] N-hydroxy-benzamidines

[0385]From benzonitrile (4g, 38.9mmol), hydroxylamine hydrochloride (8.89ml, 44.0mmol) and sodium hydroxide (4.49ml, 45.0mmol) in ethanol (30ml) N-hydroxy-benzamidine (4.83g, 91%, white solid) was obtained.¹HNMR(CDCl₃) δ (ppm): 8.81 (broad, 1H)7.63(m, 2H), 7.39(m, 3H), 4.91(s, 2H).

[0386]Example 8

[0387] N-hydroxy-3-methyl-benzamidine

[0388]From m-tolunitrile (3g, 26.0mmol), hydroxylamine hydrochloride (5.9ml, 29.6mmol), and sodium hydroxide (3.0ml, 29.9mmol) in ethanol (20ml) was obtained N-hydroxy-3-methyl-benzamidine 3.65g, 94%, as a white solid.¹H NMR(CDCl₃) δ (ppm): 8.25 (broad, 1H), 7.36(m, 2H), 7.25(m, 2H), 4.88(s, 2H), 2.38(s, 3H).

[0389]Example 9

[0390] 3-cyano-N-hydroxy-benzamidine

[0391]From isophthalonitrile (2g, 15.6mmol) in ethanol (20ml), hydroxylamine hydrochloride (3.12ml, 5M, 15.6mmol) and sodium hydroxide (15.6ml, 1M, 15.6mmol) 3-cyano-N-hydroxy-benzamidine (1.32g, 52%, white solid) was obtained. Purification was accomplished by flash column chromatography using 20-50% ethyl acetate in hexanes.¹H NMR(DMSO)，δ(ppm)：9.91(s，1H)，8.06(s，1H)，8.01(d，1H)，7.85(d，1H)，7.59(t，1H)，6.01(bs，2H)。

[0392]1 example 10

[0393] 5-chloromethyl-3- (3-methoxy-phenyl- [1, 2, 4] oxadiazole

[0394]Chloroacetyl chloride (0.72ml, 9.03mmol) and triethylamine (1.50ml, 10.23mmol) were added to N-hydroxy-3-methoxy-benzamidine (1g, 6.02mmol) in dichloromethane (12.0ml) at 0 ℃, and the resulting mixture was stirred for 20 minutes. To cyclize to form oxadiazole, after concentration of the solution, DMF (20ml) was added to the remaining portion and heated at 120 ℃ for 5 hours. The product was purified by flash chromatography using 10-20% ethyl acetate in hexanes to give the title compound (yellow oil) 0.90g (2 steps 66% yield).¹H NMR(CDCl₃)，δ(ppm)：7.68(m，1H)，7.60(d，1H)，7.40(t，1H)，7.07(m，1H)，4.76(s，2H)，3.88(s，3H)。

[0395] Examples 11-14 were prepared in a similar manner to the procedure given in example 10.

[0396]Example 11

[0397] 5-chloromethyl-3-phenyl- [1, 2, 4] oxadiazole

[0398]From chloroacetyl chloride (1.76ml, 22.05mmol) and triethylamine (3.32ml, 24.99mmol) and N-hydroxy-benzamidine (2g, 14.7mmol) in dichloromethane (29.3ml) 5-chloromethyl-3-phenyl- [1, 2, 4-methyl chloride was obtained]Oxadiazole (1.62g, 2 step 57% yield, yellow oil). Purification was accomplished via flash chromatography using 10% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.08(m，2H)，7.51(m，3H)，4.76(s，2H)。

[0399] Example 12

[0400] 5-chloromethyl-3-m-tolyl- [1, 2, 4] oxadiazole

From chloroacetyl chloride (1.59ml, 20.0mmol) and triethylamine (3.00ml, 22.7mmol) and N-hydroxy-3-methyl-benzamidine (2g, 13.3mmol) in dichloromethane (26.6ml) gave 5-chloromethyl-3-m-tolyl- [1, 2, 4 mmol ]Oxadiazole (1.75g, 2 step 62% yield, yellow oil). Purification was accomplished via flash chromatography using 10% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.90(s，1H)，7.87(s，1H)，7.36(m，2H)，4.75(s，2H)，2.34(s，3H)

[0402]Example 13

[0403]3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -benzonitrile

[0404]From 2-chloro-N-hydroxy-acetamidine (4.05g, 37.4mmol) and 3-cyanobenzoyl chloride (6.2g, 37.4mmol) in dichloromethane (60ml) and triethylamine (6.5ml, 46.7mmol) gave 3- (3-chloromethyl- [ 12, 4-chloromethyl)]Oxadiazol-5-yl) -benzonitrile (3.57g, 43%). Purification was accomplished by silica gel chromatography.¹H NMR(CDCl₃)，δ(ppm)：8.47(bs，1H)，8.41(dd，1H)，7.91(dd，1H)，7.72(1；，1H)，4.70(s，2H)；GC-MS(M+)：219。

[0405]Example 14

[0406]3- (5-chloromethyl- [1, 2, 4] oxadiazol-3-yl) -benzonitrile

[0407]3- (5-chloromethyl- [1, 2, 4)]Oxadiazol-3-yl) -benzonitrile (1.2g, 87%, light brown solid): 3-cyano-N-hydroxy-benzamidine (1.0g, 6.2mmol), triethylamine (1.5ml, 10.6mmol) and chloroacetyl chloride (0.74ml, 9.3mmol) in dichloromethane (12 ml). Purification was accomplished by silica gel decolorization.¹HNMR(CDCl₃)，δ(ppm)：8.40(s，1H)，8.32(d，1H)，7.82(d，1H)，7.64(t，1H)，4.77(s，2H)。

[0408]Example 15

[0409] 3-chloromethyl-5-m-tolyl- [1, 2, 4] oxadiazole

[0410]To a solution of 3-methyl-benzoyl chloride (0.80ml, 6.1mmol) in 2-chloro-N-hydroxy-acetamidine (440mg, 4.1mmol) in dichloromethane (10ml) was added at room temperature and the resulting mixture was stirred for 30 min. Triethylamine (0.62ml, 4.5mmol) was then added, and the resulting mixture was stirred for 30 minutes. The product was partitioned into the dichloromethane phase and the organic layer was washed with water and brine and dried over sodium sulfate. Evaporation of the solvent and flash chromatography on silica gel (10-20% ethyl acetate in hexanes) gave the intermediate as an acyclic ester (814 mg). The solution of the intermediate in DMF (10ml) was heated at 135 ℃ for 4 hours. The product was partitioned into ethyl acetate phase, the organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. Evaporation of the solvent and flash chromatography on silica gel (5% ethyl acetate in hexane) gave 3-chloromethyl-5-m-tolyl- [1, 2, 4 ]Oxadiazole (469mg, 2 step 54%, white solid).¹H NMR(CDCl₃)，δ(ppm)：7.99(s，1H)，7.97(m，1H)，7.43(d，2H)，4.68(s，2H)，2.45(s，3H)。

[ [0411] example 16

[0412] 3-chloromethyl-5- (3-fluoro-phenyl-) - [1, 2, 4] oxadiazole

[0413]DMF (10ml) was added to a mixture of 3-fluorobenzoic acid (710mg, 5.07mmol), 1- (3-dimethylaminopropyl) -3-Ethylcarbodiimide (EDCDI) (972mg, 5.07mmol), 1-hydroxybenzotriazole hydrate (HOBt) (685mg, 5.07mmol) and 2-chloro-N-hydroxy-acetamidine (500mg, 4.61mmol) at room temperature, followed by stirring overnight. The reaction mixture was diluted with ethyl acetate, washed with water (3 times) and brine, dried over anhydrous sodium sulfate, filtered and concentrated. To cyclize to form oxadiazole, DMF (14ml) was added to the remaining portion and the resulting solution was heated at 135 ℃ for 3.5 hours. After cooling the reaction mixture, it was washed with water (3 times) and brine, dried over anhydrous sodium sulfate, filtered and concentrated. Make itFlash chromatography on silica gel with 5% ethyl acetate in hexane afforded 3-chloromethyl-5- (3-fluoro-phenyl) - [1, 2, 4%]Oxadiazole (383mg, 2 step 35% yield, yellow oil).¹H NMR(CDCl₃)，δ ppm)：7.96(d，1H)，7.86(m，1H)，7.54(m，1H)，7.33(m，1H)，4.68(s，2H)。

[0414] Examples 17-30 were prepared in a similar manner to the procedure given in example 16.

[0415]Example 17

[0416] 3-chloromethyl-5-thiophen-3-yl- [1, 2, 4] oxadiazole

[0417]From 3-thiophenecarboxylic acid (700mg, 4.96mmol), EDCI (950mg, 4.96mmol), HOBt (670mg, 4.96mmol) and 2-chloro-N-hydroxy-acetamidine (538mg, 5.46mmol) in DMF (10ml) 3-chloromethyl-5-thiophen-3-yl- [1, 2, 4mmol)]Oxadiazole (197mg, 2 step 20% yield, white solid). The acyclic product was purified via flash column chromatography, eluting with 2: 1.2: 0.8 dichloromethane: hexane: ethyl acetate. The title compound was purified via flash column chromatography using 5% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.28(s，1H)，7.70(d，1H)，7.48(m，1H)。

[0418]Example 18

[0419]3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -5-methyl-pyridine

[0420] From 5-methylnicotinic acid (472mg, 3.44mmol), EDCI (652mg, 3.44mmol), HOBt (465mg, 3.44mmol) and 2-chloro-N-hydroxy-acetamidine (340mg, 3.13mmol) in DMF (10ml) gave 3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -5-methyl-pyridine (25mg, 2 step 4% yield). Purifying the acyclic intermediate via flash column chromatography using 100% ethyl acetate; as a by-product, 200mg (30%) of the acyclic ester was also isolated.

[0421]Example 19

[0422] 3-chloromethyl-5- (3-nitro-phenyl) - [1, 2, 4] oxadiazole

[0423]From 3-nitrobenzoic acid (847mg, 5.07mmol), EDCI (972mg, 5.07mmol), HOBt (685mg, 5.07mmol) and 2-chloro-N-hydroxy-acetamidine (500mg, 4.61mmol) in DMF (10ml) gave 3-chloromethyl-5- (-3-nitro-phenyl) - [1, 2, 4 ]Oxadiazole (335mg, 2 step 30% yield, yellow solid). The acyclic intermediate was purified via flash column chromatography using 100% ethyl acetate. Purification was achieved via flash column chromatography using 15% ethyl acetate in hexanes.¹HNMR(CDCl₃)，δ(ppm)：9.03(t，1H)，8.50(t，2H)，7.79(t，1H)，4.71(s，2H)。

[0424]Example 20

[0425]4- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl-) -2-methyl-pyridine

[0426]From 6-methylpyridine-4-carboxylic acid (800mg, 5.8mmol), EDCI (1.12g, 5.8mmol), HOBt (788mg, 5.8mmol) and 2-chloro-N-hydroxy-acetamidine (575mg, 5.3mmol) in DMF (10ml) plus triethylamine (536mg, 5.3mmol) 4- (3-chloromethyl- [1, 2, 4 mmol)]Oxadiazol-5-yl) -2-methyl-pyridine (316mg, 2 step 28% yield, yellow oil). Purification was achieved via flash column chromatography using 30% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.75(d，1H)，7.88(s，1H)，7.79(d，1H)，4.70(s，2H)，2.70(s，3H)。

[0427]Example 21

[0428] 3-chloromethyl-5- (3-ethyl-phenyl) - [1, 2, 4] oxadiazole

[0429]From 3-ethylbenzoic acid (770mg, 3.81mmol), EDCI (803mg, 4.19mmol), HOBt (566mg, 4.19mmol) and 2-chloro-N-hydroxy-acetamidine (454mg, 4.19mmol) in DMF (10ml) gave 3-chloromethyl-5- (3-ethyl-phenyl) - [1, 2, 4 mmol)]Oxadiazole (446mg, 2 step 52% yield, yellow oil). Purification was achieved via flash column chromatography using 5% ethyl acetate in hexanes. ¹H NMR(CDCl₃)，δ(ppm)：7.96(t，2H)，7.42(m，2H)，4.68(s，2H)，2.74(m，2H)，1.28(m，3H)。

[0430]Example 22

[0431]3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -phenyl ] -dimethylamine

[0432]From 3- (dimethylamino) benzoic acid (656mg, 3.97mmol), EDCI (761mg, 3.97mmol), HOBt (536mg, 3.97mmol) and 2-chloro-N-hydroxy-acetamidine (500mg, 3.6mmol) in DMF (10ml) 3- (3-chloromethyl- [1, 2, 4 mmol) was obtained]Oxadiazol-5-yl) -phenyl]Dimethylamine (40mg, 2 step 4% yield, yellow solid). Purification was achieved via flash column chromatography using 5% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.46(t，2H)，7.37(t，1H)，6.94(d，1H)，4.68(s，2H)，3.04(s，6H)。

[0433]Example 23

[0434] 3-chloromethyl-5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole

[0435]From 3-chlorobenzoic acid (708mg, 4.52mmol), EDCI (866mg, 4.52mmol), HOBt (611mg, 4.52mmol) and 2-chloro-N-hydroxy-acetamidine (446mg, 4.11mmol) in DMF (10ml) gave 3-chloromethyl-5- (3-chloro-phenyl) - [1, 2, 4 mmol)]Oxadiazole (406mg, 2 step 43% yield, white solid). Purification was achieved via flash column chromatography using 5% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.17(t，1H)，8.05(d，1H)，7.59(t，1H)，7.50(t，1H)，4.68(s，2H)。

[0436]Example 24

[0437] 3-chloromethyl-5- (3-trifluoromethoxy-phenyl) - [1, 2, 4] oxadiazole

[0438]From 3-trifluoromethoxybenzoic acid (1.05g, 5.07mmol), EDCI (972mg, 5.07mmol), HOBt (685mg, 5.07mmol) and 2-chloro-N-hydroxy-acetamidine (500mg, 4.61mmol) in DMF (10ml) gave 3-chloromethyl-5- (3-trifluoromethoxy-phenyl) - [1, 2, 4] methyl chloride ]Oxadiazole (707 m)g, 2 step 55% yield, light yellow oil). Purification was achieved via flash column chromatography using 5% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.10(m，1H)，8.03(s，1H)，7.61(t，1H)，7.48(d，1H)，4.69(s，2H)。

[0439] Example 25

[0440]5- (3-bromo-phenyl) -3-chloromethyl- [1, 2, 4] oxadiazole

[0441]From 3-bromobenzoic acid (1.05g, 5.07.mmol), EDCI (972mg, 5.07mmol), HOBt (685mg, 5.07mmol) and 2-chloro-N-hydroxy-acetamidine (500mg, 4.61mmol) in DMF (10ml) 5- (3-bromo-phenyl) -3-chloromethyl- [1, 2, 4]Oxadiazole (707mg, 2 step 55% yield, white solid). Purification was achieved via flash column chromatography using 5% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.10(m，1H)，8.03(s，1H)，7.61(t，1H)，7.48(d，1H)，4.69(s，2H)。

[0442]Example 26

[0443] 3-chloromethyl-5-thiophen-2-yl- [1, 2, 4] oxadiazole

[0444]From thiophene-2-carboxylic acid (649mg, 5.1mmol), 2-chloro-N-hydroxy-acetamidine (500mg, 4.6mmol), EDCI (972mg, 5.1mmol) and HOBt (684mg, 5.1mmol) in DMF (5ml) 3-chloromethyl-5-thiophen-2-yl- [1, 2, 4-d]Oxadiazole (202mg, 20%, off-white solid). Purification was achieved via SPE (flash) chromatography using 5% ethyl acetate in hexanes.¹HNMR(CDCl₃)，δ(ppm)：8.00(s，1H)，7.83(d，1H)，7.19(t，1H)，4.13(s，2H)。

[0445]EXAMPLE 27

[0446] 3-chloromethyl-5- (3-fluoro-5-methyl-phenyl) - [1, 2, 4] oxadiazole

[0447]From 3-fluoro-5-methyl-benzoic acid (469mg, 3.0mmol), 2-chloro-N-hydroxy-acetamidine (363mg, 3.3mmol), EDCI (641mg, 3.3mmol) and HOBt (452mg, 3.3mmol) in DMF (5ml) To obtain 3-chloromethyl-5- (3-fluoro-5-methyl-phenyl) - [1, 2, 4]Oxadiazole (312mg, 46%, colorless oil). Purification was achieved via SPE (flash) chromatography using 5% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(pppm)：7.79(s，1H)，7.65(d，1H)，7.15(d，1H)，4.67(s，2H)，2.46(s，3H)。

[0448]Example 28

[0449] 3-chloromethyl-5-thiazol-4-yl- [1, 2, 4] oxadiazole

[0450]3-chloromethyl-5-thiazol-4-yl- [1, 2, 4-yl ] thiazol-4-yl- [1, 2, 4, 3mmol ] was obtained from thiazole-4-carboxylic acid (500mg, 3.9mmol), 2-chloro-N-hydroxy-acetamidine (462mg, 4.3mmol), EDCI (817mg, 4.3mmol) and HOBt (575mg, 4.3mmol) in DME (5ml)]Oxadiazole (37mg, 5%, yellow solid). Purification was achieved via SPE (flash) chromatography using 30% ethyl acetate in hexanes.¹HNMR(CDCl₃)，δ(ppm)：9.02(d，1H)，8.42(d，1H)，4.70(s，2H)。

[0451]Example 29

[0452] 3-chloromethyl-5- (3-iodo-phenyl) - [1, 2, 4] oxadiazole

[0453]From 3-iodo-benzoic acid (5.0g, 20.2mmol), 2.4g, 22.2mmol 2-chloro-N-hydroxy-acetamidine, EDCI (4.3g, 22.2mmol) and HOBt (3.0g, 22.2mmol) in DMF (10ml) 3-chloromethyl-5- (3-iodo-phenyl) - [1, 2, 4 mmol)]Oxadiazole (2.9g, 44%, white solid). The intermediate acyclic ester is purified by flash column chromatography using 50-80% ethyl acetate in hexanes. The title compound was purified by SPE (flash) chromatography using 5% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.52(s，1H)，8.13(d，1H)，7.96(d，1H)，7.29(t，1H)，4.68(s，2H)。

[0454]Example 30

[0455] 3-chloromethyl-5- (3-methoxymethyl-phenyl) - [1, 2, 4] oxadiazole

[0456]From 3-methoxymethylbenzoic acid (395mg, 2.4mmol), 2-chloro-N-hydroxy-acetamidine (284mg, 2.6mmol), EDCI (501mg, 2.6mmol) and HOBt (353mg, 2.6mmol) in DMF (5ml) gave 3-chloromethyl-5- (3-methoxymethyl-phenyl) - [1, 2, 4] a]Oxadiazole (193mg, 34%, pale yellow oil). Purification was achieved via SPE (flash) chromatography using 5% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.14(s，1H)，8.08(d，1H)，7.61(d，1H)，7.53(t，1H)，4.68(s，2H)，4.54(s，2H)，3.44(s，3H)。

[0457]Example 31

[0458] 5-furan-2-yl-4-methyl-4H- [1, 2, 4] triazole-3-thiol

[0459]2-Furanoyl chloride (0.76ml, 7.66mmol) was added dropwise to a solution of 4-methyl-3-thiosemicarbazide (732mg, 6.96mmol) and pyridine (7ml), and the resulting solution was stirred at room temperature for 4 hours. The reaction mixture was diluted with ethyl acetate (100ml), washed successively with water (3X 100ml) and brine (100ml), the organic phase dried (sodium sulphate), filtered and concentrated in vacuo. The remaining portion was suspended in sodium bicarbonate (70ml, 69.6mmol, 1M water) and stirred at 100 ℃ overnight. The reaction mixture was cooled to 0 ℃ and then the pH was adjusted to about 6 using hydrochloric acid (70ml, 1N water). The title compound (298mg) was collected by filtration as a white solid. ¹H NMR(CDCl₃)，δ(ppm)：11.4(bs，1H)，7.63(d，1H)，7.02(d，1H)，6.60(dd，1H)，3.83(s，3H)。

[0460] Examples 31-35 were prepared in a similar manner to the procedure given in example 31.

[0461]Example 32

[0462] 4-methyl-5-phenyl-4H- [1, 2, 4] triazole-3-thiol

[0463]From 4-methyl-3-thiosemicarbazide (732mg, 6.96mmol) and pyridine (7ml) with benzoyl chloride (0.89ml, 7.66mmol) 4-methyl-5-phenyl-4H- [1, 2, 4 mmol) was obtained]Triazole-3-thiol (478mg, off-white solid). Then add intoSodium bicarbonate (70ml, 69.6mmol, 1M water) at 100 ℃ overnight, the title compound was collected by filtration.¹H NMR(CDCl₃)，δ(ppm)：12.3(bs，1H)7.55(m，5H)，3.65(s，3H)。

[0464]Example 33

[0465] 4-methyl-5-pyridin-2-yl-4H- [1, 2, 4] triazole-3-thiol

[0466]From 4-methyl-3-thiosemicarbazide (537mg, 5.11mmol) and pyridine (7ml) with 2-pyridinecarbonyl chloride hydrochloride (1.00g, 5.62mmol) 4-methyl-5-pyridin-2-yl-4H- [1, 2, 4]Triazole-3-thiol (44mg, pale green solid). Sodium bicarbonate (51ml, 1M water) was then added and the title compound was collected using extraction and evaporation at 100 ℃ overnight.¹H NMR(CDCl₃)，δ(ppm)：11.1(bs，1H)，8.70(d，1H)，8.02(d，1H)，7.84(m，1H)，7.41(dd，1H)，4.05(s，3H)。

[0467]Example 34

[0468]5- (4-benzyl-morpholin-2-yl) -4-methyl-4H- [1, 2, 4] triazole-3-thiol

[0469]From 4-methyl-3-thiosemicarbazide (346mg, 3.29mmol) and pyridine (7ml) with 4-benzyl-2-morpholinocarbonyl chloride hydrochloride (1.00g, 3.62mmol) was obtained (83.3mg, as a cloudy yellow solid). Sodium bicarbonate (33ml, 1M water) was then added and the title compound was collected using extraction and evaporation at 100 ℃ overnight. ¹HNMR(CDCl₃)，δ(ppm)：9.48(bs，1H)，7.25(m，5H)，4.68(dd，1H)，3.86(dAb，1H)，3.68(tAB，1H)，3.59-3.64(m，5H)，3.07(d，1H)，2.88(d，1H)，2.61(t，1H)，2.37(dt，1H)。

[0470]Example 35

[0471] 5-tert-butyl-4-methyl-4H- [1, 2, 4] triazole-3-thiol

[0472]From 4-methyl-3-thiosemicarbazide (1.80g, 17.2mmol) and pyridine (20ml) with trimethylacetyl chloride (1.92ml, 15.6mmol) 5-tert-butyl-4-methyl-4H- [1, 2, 4]Triazole-3-thiol (2.21g, 83%, off-white solid). Sodium hydroxide (200ml, 5% water) was then added, stirred at 60 ℃ overnight, and the title compound was collected by extraction and evaporation.¹H NMR(CDCl₃)，δ(ppm)：11.7(bs，1H)，3.72(s，3H)1.40(s，9H)。

[0473]Example 36

[0474] 4-methyl-5-pyridin-3-yl-4H- [1, 2, 4] triazole-3-thiol

[0475]A solution of 4-methyl-3-thiosemicarbazide (902mg, 8.58mmol), nicotinic acid (960mg, 7.80), EDCI (1.64g, 8.58mmol) and HOBt (1.16g, 8.58mmol) in DMF (10ml) was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (100ml) and washed successively with hydrochloric acid (50ml, 10% aqueous), water (50ml), saturated sodium carbonate (50ml, aqueous), water (50ml) and brine. The organic phase was dried (sodium sulfate), filtered and concentrated in vacuo. The remaining portion was stirred in sodium hydroxide (53.4ml, 66.7mmol, 5% aqueous) at 60 ℃ overnight. The reaction mixture was cooled to 0 ℃ and the pH was carefully adjusted to about 6 with hydrochloric acid (1N water). The aqueous phase was saturated with solid sodium chloride and then extracted with ethyl acetate (4X 50 ml). The organic phases were combined and washed with brine (100ml), dried (sodium sulfate), filtered and concentrated in vacuo. (180mg, off-white solid). ¹H NMR(CDCl₃)，δ(ppm)：11.6(bs，1H)，8.94(s，1H)，8.83(dd，1H)，7.98(m，1H)，7.51(dd，1H)，3.69(s，3H)。

[0476] Examples 37-39 were prepared in a similar manner to the procedure given in example 36.

[0477]Example 37

[0478] 4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazole-3-thiol

[0479]From 4-methyl-3-thiosemicarbazide (902mg, 8.58mmol), 3-thiophenecarboxylic acid (1g, 7.80mmol), EDCI (1.64g, 8.58mmol), HOBt (1.16g, 8.58mmol) in DMF (10ml) 4-methyl-5-thiophen-3-yl-4H- [1, 2, 4]Triazole-3-thiol (693mg, white solid). Then sodium hydroxide (88ml, 110mmol, 5% aqueous) was collected by extraction and evaporation at 60 ℃ overnight.¹H NMR(CDCl₃)，δ(ppm)：11.4(bs，1H)，7.77(dd，1H)，7.51(dd，1H)，7.42(dd，1H)，3.61(s，3H)。

[0480]Example 38

[0481] 4-methyl-5-thiazol-4-yl-4H- [1, 2, 4] triazol-3-thiol

[0482] From 4-methyl-3-thiosemicarbazide (902mg, 8.58mmol), 4-carboxythiazole (1.01g, 7.80), EDCI (1.64g, 8.58mmol), HOBt (1.16g, 8.58mmol) in DMF (10ml) was obtained 4-methyl-5-thiazol-4-yl-4H- [1, 2, 4] triazole-3-thiol (71.2mg, viscous yellow oil).

Sodium hydroxide (43ml, 54mmol, 5% aqueous) was then used overnight at 60 ℃ to collect the title compound by extraction and evaporation.

[0483]Example 39

[0484] 5-cyclohexyl-4-methyl-4H- [1, 2, 4] triazole-3-thiol

[0485] From 4-methyl-3-thiosemicarbazide (1.80g, 17.2mmol), cyclohexanecarboxylic acid (2g, 15.6mmol), EDCI (2.99g, 17.2mmol) and HOBt (2.10g, 17.2mmol) in DMF (20ml) was obtained 5-cyclohexyl-4-methyl-4H- [1, 2, 4] triazole-3-thiol (403mg, light brown solid). Then sodium hydroxide (195ml, 244mmol, 5% aqueous) at 60 ℃ overnight.

[0486]Example 40

[0487]2- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl- ] 1H-benzimidazole

[0488]1H-benzimidazole-2-thiol (150mg, 1mmol) was added to 3-chloromethyl-5- (3-methoxy-phenyl) - [1, 2, 4] dissolved in DMF (2ml) at room temperature]Oxadiazole (30mg, 0.13mmol) and potassium carbonate (50mg, 0.36 mmol). The solvent was removed in vacuo and the mixture was,the product is obtained by flash chromatography using 20-100% ethyl acetate in hexane.¹H NMR(CDCl₃) δ (ppm): 7.71(d, 1H), 7.62(d, 1H), 7.53(m, 2H), 7.42(t, 1H), 7.18 (overlap, m, 3H), 4.52(s, 2H), 3.87(s, 3H).

Using a similar procedure to the procedure given in example 40, examples 41-92 were prepared

[0489]EXAMPLE 41

[0490]5- (3-methoxy-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0491]From 3-chloromethyl-5- (3-methoxy-phenyl- [1, 2, 4] in acetonitrile (1ml) at room temperature]Oxadiazole (50mg, 0.22mmol), Potassium carbonate (92.4mg, 0.67mmol), 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (52.8mg, 0.27mmol) gave the title compound. Purification was achieved by SPE (flash) chromatography using 30-40% ethyl acetate in hexanes to give 76mg (90%) of the title compound as a white solid. ¹H NNR(CDCl₃)，δ(ppm)：7.68(d，1H)，7.57(t，1H)，7.49(m，2H)，7.41(t，1H)，7.15(m，2H)，4.53(s，2H)，3.85(s，3H)，3.72(s，3H)。LC-MS(M+1)+386.3。

[0492]Example 42

[0493]3- [5- (1-methyl-5-thiophen-2-yl-1H-imidazol-2-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-3-yl ] -benzonitrile

[0494]From 3-chloromethyl-3- (5-chloromethyl- [1, 2, 4] methyl chloride in acetonitrile (1ml) at room temperature]Oxadiazol-3-yl) -benzonitrile (50mg, 0.22mmol), Potassium carbonate (92.4mg, 0.67mmol), 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (52.8mg, 0.27mmol) gives 3- [5- (1-methyl-5-thiophen-2-yl-1H-imidazol-2-ylsulfanylmethyl) - [1, 2, 4]Oxadiazol-3-yl]Benzonitrile (39mg, 47%, white solid). Purification was achieved by SPE (flash) chromatography using 50-70% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ (ppm): 8.34(s, 1H), 8.28(d, 1H), 7.79(d, 1H), 7.60(t, 1H), 7.53(d, 1H), 7.49(d, 1H), 7.19(m, 1H), 4.70(s, 2H), 3.74(s, 3H). LS-MS (ES + complete Scan, C)₁₇H₁₂N₆OS₂)M⁺Calculated value 380.05, found value (M +1)⁺381.04。

[0495] Example 43

[0496]3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-phenyl- [1, 2, 4] oxadiazole

[0497]3-chloromethyl-5-phenyl- [1, 2, 4] from acetonitrile (2ml) at 60 ℃ overnight]Oxadiazole (50mg, 0.26mmol), Potassium carbonate (106mg, 0.77mmol), 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4 ]Triazole-3-thiol (60.8mg, 0.31mmol) gives 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-phenyl- [1, 2, 4]Oxadiazole (41.2mg, 44%, off-white solid). Purification was achieved on silica gel using 50% ethyl acetate in hexanes.¹HNMR(CDCl₃)，δ(ppm)：8.09(m，2H)，7.57(m，5H)，7.17(dd，1H)，4.53(s，2H)，3.72(s，3H)。

[0498]Example 44

[0499]2- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -5-methyl-1H-benzimidazole

[0500]From 3-chloromethyl-5- (3-methoxy-phenyl- [1, 2, 4] in acetonitrile (3ml) at room temperature]Oxadiazole (82mg, 0.365mmol), Potassium carbonate (210mg, 1.520mmol), 2-mercapto-5-methyl-1H-benzimidazole (50mg, 0.305mmol) to give 2- [5- (3-methoxy-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethylthio]-5-methyl-1H-benzimidazole (75.5mg, 70.5%, white foam). Purification was achieved by SPE (flash) chromatography with 50% ethyl acetate in hexanes followed by trituration with ethyl acetate.¹H NMR(CDCl₃)，δ(ppm)：11.95(bs，1H)，7.80(d，1H)，7.70(s，1H)，7.52(m，2H)，7.21(dd，2H)，7.17(d，1H)，4.40(s，2H)，3.95(s，3H)，2.50(s，3H)。

[0501]Example 45

[0502]3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole

[0503]From 3-chloromethyl-5-m-tolyl- [1, 2, 4] in acetonitrile (1ml) at room temperature]Oxadiazole (50mg, 0.24mmol), Potassium carbonate (99.4mg, 0.72mmol), 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4 ]Triazole-3-thiol (56.7mg, 0.27mmol) gives 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (76mg, 85%, white solid). Purification was achieved by SPE (flash) chromatography using 50-70% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.89(m，2H)，7.50(m，2H)，7.40(m，2H)，7.18(t，1H)，4.52(s，2H)，3.71(s，3H)，2.41(s，3H)。

[0504]Example 46

[0505]3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-trifluoromethyl-phenyl) - [1, 2, 4] oxadiazole

[0506]From 3-chloromethyl-5- (3-trifluoromethyl-phenyl-) - [1, 2, 4] in acetonitrile (1ml) at room temperature]Oxadiazole (60mg, 0.23mmol), Potassium carbonate (95mg, 0.69mmol), and 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (54mg, 0.27mmol) gives 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (3-trifluoromethyl-phenyl) - [1, 2, 4]Oxadiazole (84mg, 86%, white solid). Purification was achieved by SPE (flash) chromatography using 40-60% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.38(s，1H)，7.29(d，1H)，7.86(d，1H)，7.68(t，1H)，7.50(t，2H)，7.19(m，1H)，4.57(s，2H)，3.75(s，3H)。

[0507]Example 47

[0508]3- (3-methoxy-phenyl) -5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0509]From 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] in acetonitrile (1ml) at room temperature ]Triazole-3-thiol (53.3mg, 0.27mmol), 5-chloromethyl-3- (3-methoxy-phenyl) - [1, 2, 4]Oxadiazole (50mg, 0.22 mmol), and potassium carbonate (92.6mg, 0.67mmol) to give 3- (3-methoxy-phenyl) -5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazole (74.3mg, 88%, white solid). Purification was achieved by SPE (flash) chromatography using 40-70% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.62(d，1H)，7.52(d，2H)，7.48(d，1H)，7.37(t，1H)，7.18(t，1H)，7.06(m，1H)，4.64(s，2H)，3.84(s，3H)，3.71(s，3H)。LC-MS(MH+)：386.06。

[0510]Example 48

[0511]5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-phenyl- [1, 2, 4] oxadiazole

[0512]From 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] in acetonitrile (1ml) at room temperature]Triazole-3-thiol (86.8mg, 0.44mmol), 5-chloromethyl-3-phenyl- [1, 2, 4]Oxadiazole (50mg, 0.26mmol) and potassium carbonate (152.0mg, 1.1mmol) to give 5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -3-phenyl- [1, 2, 4]Oxadiazole (79.9mg, 87%, white solid). Purification was achieved by SPE (flash) chromatography using 40-70% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.02(d，2H)，7.47(m，5H)，7.18(t，1H)。

[0513]Example 49

[0514]5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3-m-tolyl- [1, 2, 4] oxadiazole

[0515]From 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] in acetonitrile (1ml) at room temperature]Triazole-3-thiols(78.9mg, 0.40mmol), 5-chloromethyl-3-m-tolyl- [1, 2, 4]Oxadiazole (50mg, 0.24mmol) and potassium carbonate (138.2mg, 1.0mmol) gave 5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -3-m-tolyl- [1, 2, 4]Oxadiazole (71.8mg, 91%, white solid). Purification was achieved by SPE (flash) chromatography using 45-65% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.82(d，2H)，7.52(d，1H)，7.47(d，1H)，7.31(m，2H)，7.18(m，1H)，4.64(s，2H)，3.70(s，3H)，2.39(s，3H)。LC-MS(MH⁺)：370.06。

[0516]Example 50

[0517]3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -benzonitrile

[0518]Reaction of 3- (3-chloromethyl- [1, 2, 4] methyl acetate in acetonitrile at room temperature]Oxadiazol-5-yl) -benzonitrile (100mg, 0.45mmol) with K₂CO₃(189mg, 1.36mmol) and 4-methyl-5- (2-thienyl) [1, 2, 4]]Triazole-3-thiol (110mg, 0.54mmol) gives 3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]Benzonitrile (130mg, 75%). Purification was achieved via flash chromatography using 50% ethyl acetate in dichloromethane.¹HNMR(CDCl₃)，δ(ppm)：8.38(bs，1H)，8.32(d，1H)，7.88(d，1H)，7.68(t，H)，7.51(dd，2H)，7.18(dd，1H)，4.56(s，2H)，3.75(s，3H)；LC-MS(M+H)⁺：381。

[0519]Example 51

[0520]3- [ 4-methyl-5- (2-methyl-thiazol-4-yl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole

[0521]3-chloromethyl-5-m-tolyl- [1, 2, 4] in acetonitrile (2ml) at 60 ℃ overnight]Oxadiazole (50mg, 0.24mmol), Potassium carbonate (99mg, 0.72mmol), 4-methyl-5- (2-methyl-thiazol-4-yl) -4H- [1, 2, 4]Triazole-3-thiol (61mg, 0.29)mmol) to obtain 3- [ 4-methyl-5- (2-methyl-thiazol-4-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-5-m-tolyl- [1, 2, 4]Oxadiazole (82.8mg, 90%, white solid). Purification was achieved on silica gel using 80% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.96(s，1H)，7.88(m，2H)，7.38(m，2H)，4.53(s，2H)，3.91(s，3H)，2.75(s，3H)，2.41(s，3H)。

[0522]Example 52

[0523]3- [5- (2-methyl-thiazol-4-yl) - [1, 3, 4] oxadiazol-2-ylsulfanylmethyl ] -5-m-tolyl- [1, 2, 4] oxadiazol

[0524]3-chloromethyl-5-m-tolyl- [1, 2, 4] in acetonitrile (2ml) at 60 ℃ overnight]Oxadiazole (50mg, 0.24mmol), Potassium carbonate (99mg, 0.72mmol), 5- (2-methyl-thiazol-4-yl) [1, 3, 4]]Triazole-2-thiol (57.3mg, 0.29mmol) gives 3- [5- (2-methyl-thiazol-4-yl) - [1, 3, 4]]Oxadiazol-2-ylthiomethyl]-5-m-tolyl [1, 2, 4]]Oxadiazole (89mg, 99%, off-white solid). Purification was achieved on silica gel using 80% ethyl acetate in hexanes.¹HNMR(CDCl₃)，δ(ppm)：7.97(s，1H)，7.90(m，2H)，7.40(m，2H)，4.66(s，2H)，2.80(s，3H)，2.42(s，3H)。

[0525]Example 53

[0526]3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiophen-2-yl- [1, 2, 4] oxadiazole

[0527]In acetonitrile (1ml) at room temperature, from 3-chloromethyl-5-thiophen-2-yl- [1, 2, 4]Oxadiazole (50mg, 0.25mmol), Potassium carbonate (103mg, 0.75mmol), 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (59mg, 0.30mmol) gives 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-thiophen-2-yl- [1, 2, 4]Oxadiazole (80mg, 88%, white solid). Purification was achieved by SPE (flash) chromatography using 50-70% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.89(d，1H)，7.65(m，1H)，7.51(m，2H)，7.19(m，2H)，4.50(t，2H)，3.74(s，3H)。

[0528]Example 54

[0529]3- [5- (2, 4-dimethyl-thiazol-5-yl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole

[0530]3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (50mg, 0.24mmol), Potassium carbonate (99mg, 0.72mmol) and 5- (2, 4-dimethyl-thiazol-5-yl) -4-methyl-4H- [1, 2, 4]Triazole-3-thiol (65.1mg, 0.29mmol) in acetonitrile (2ml) at 60 ℃ overnight to give 3- [5- (2, 4-dimethyl-thiazol-5-yl) -4-methyl-4H- [1, 2, 4 ℃]Triazol-3-ylthiomethyl]-5-m-tolyl- [1, 2, 4]Oxadiazole (54.2mg, 57%, off-white solid). Purification was achieved on silica gel using 80% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.88(m，2H)，7.39(m，2H)，4.57(s，2H)，3.49(s，3H)，2.73(s，3H)，2.43(d，6H)。

[0531]Example 55

[0532]3- [ 4-methyl-5- (5-nitro-furan-2-yl) -4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole

[0533] From 3-chloromethyl-5-m-tolyl- [1, 2, 4] oxadiazole (50mg, 0.24mmol), potassium carbonate (99mg, 0.72mmol) and 4-methyl-5- (5-nitro-furan-2-yl) -4H- [1, 2, 4] triazole-3-thiol in acetonitrile (2ml) at 60 ℃ overnight, 3- [ 4-methyl-5- (5-nitro-furan-2-yl) -4H- [1, 2, 4] triazol-3-ylthiomethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole (77.9mg, 81%, yellow solid) was obtained. Purification was achieved on silica gel using 80% ethyl acetate in hexanes.

¹H NMR(CDCl₃，δ(ppm)：7.90(m，2H)，7.46(d，1H)，7.40(m，2H)，7.33(d，1H)，4.59(s，2H)，3.91(s，3H)，2.42(s，3H)。

[0534]Example 56

[0535]4- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine

[0536]From 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (50mg, 0.24mmol), Potassium carbonate (99mg, 0.72mmol), 4-methyl-5-pyridin-4-yl-4H- [1, 2, 4]Triazole-3-thiol (55.3mg, 0.29mmol) in acetonitrile (2ml) at 60 ℃ overnight to give 4- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4)]Oxadiazol-3-ylmethylthio) -4H- [1, 2, 4]Triazol-3-yl]Pyridine (66mg, 75%, white solid). Purification was achieved on silica gel using 80% ethyl acetate in hexanes.¹HNMR(CDCl₃)，δ(ppm)：8.79(dd，2H)，7.89(m，2H)，7.63(dd，2H)，7.40(m，2H)，4.59(s，2H)，3.69(s，3H)，2.41(s，3H)。

[0537]Example 57

[0538]3- [5- (4-tert-butyl-phenyl) -4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] -5-m-tolyl- [1, 2, 4] -oxadiazole

[0539]From 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (50mg, 0.24mmol), Potassium carbonate (99mg, 0.72mmol) and 5- (4-tert-butyl-phenyl) -4-methyl-4H- [1, 2, 4]Triazole-3-thiol (71.1mg, 0.29mmol) in acetonitrile (2ml) at 60 ℃ overnight to give 3- [5- (4-tert-butyl-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-5-m-tolyl- [1, 2, 4]Oxadiazole (100mg, 99%, white waxy solid). Purification was achieved on silica gel using 80% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.89(m，2H)，7.57(m，4H)，7.39(d，2H)，4.55(s，2H)，3.61(s，3H)，2.40(s，3H)，1.35(s，9H)。

[0540]Example 58

[0541] 2-chloro-5- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine

[0542]From 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (50mg, 0.24mmol), Potassium carbonate (99mg, 0.72mmol), 5- (6-chloro-pyridin-3-yl) -4-methyl-4H- [1, 2, 4]Triazole-3-thiol (65.2mg, 0.29mmol) in acetonitrile (2ml) at 60 ℃ overnight to give 2-chloro-5- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4)]Oxadiazol-3-ylmethylthio) -4H- [1, 2, 4]Triazol-3-yl]Pyridine (53.8mg, 56%, white solid). Purification was achieved on silica gel using 80% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.67(d，1H)，8.02(dd，1H)，7.88(m，2H)，7.49(d，1H)，7.40(m，2H)，4.58(s，2H)，3.65(s，3H)，2.42(s，3H)。

Example 59

[0543]2- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -benzoxazole

[0544]From 3-chloromethyl-5- (3-methoxy-phenyl) - [1, 2, 4]]Oxadiazole (225.9mg, 1.11mmol), benzoxazole-2-thiol (167mg, 1.00mmol) and potassium carbonate (180mg, 1.3mmol) in DMF (4.5ml) at room temperature overnight to give 2- [5- (3-methoxy-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethylthio]Benzoxazole (138mg, 62%). Purification was achieved on silica gel using 10-20% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)∷7.67(d，1H)，7.57(m，3H)，7.43(t，1H)，7.21(m，2H)，7.14(m，1H)，4.50(s，2H)，3.86(s，3H)。

[0545]Example 60

[0546]3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiophen-3-yl- [1, 2, 4] oxadiazole

[0547]In acetonitrile (1ml) at room temperature, from 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (61mg, 0.31mmol), 3-chloromethyl-5-thiophen-3-yl- [1, 2, 4]Oxadiazole (50mg, 0.28mmol) and potassium carbonate (115mg, 0.83mmol) gave 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-Thien-3-yl- [1, 2, 4]Oxadiazole (73.6mg, 73%, white solid). Purification was achieved by SPE (flash) chromatography using 50-70% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.20(d，1H)，7.64(d，1H)，7，48(m，3H)，7.18(m，1H)，4.52(s，2H)，3.72(s，3H)。

[0548]Example 61

[0549]3- (5-Furan-2-yl-4-methyl-4H- [1, 2, 4] triazol-3-ylthiomethyl) -5-m-tolyl- [1, 2, 4] oxadiazole

[0550]From 3-chloromethyl-5-m-tolyl- [1, 2, 4 ]Oxadiazole (40.0mg, 0.19mmol), Potassium carbonate (79mg, 0.58mmol) and 5-Furan-2-yl-4-methyl-4H- [1, 2, 4]Triazole-3-thiol (41.7mg, 0.23mmol) in acetonitrile (2ml) at 60 ℃ overnight to give 3- (5-furan-2-yl-4-methyl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (51.0mg, 76%, white solid). Purification was achieved on silica gel using 80% ethyl acetate in hexanes.¹HNMR(CDCl₃)，δ(ppm)：7.88(m，2H)，7.58(s，1H)，7.40(m，2H)，7.10(d，1H)，6.58(dd，1H)，4.51(s，2H)，3.77(s，3H)，2.41(s，3H)。

[0551]Example 62

[0552]5- (3-fluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0553]In acetonitrile (1ml) at room temperature, from 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (51mg, 0.26mmol), 3-chloromethyl-5- (3-fluoro-phenyl) - [1, 2, 4]Oxadiazole (50mg, 0.24mmol) and potassium carbonate (98mg, 0.71mmol) gave 5- (3-fluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazole (75.4mg, 83%, white solid). Purification was achieved by SPE (flash) chromatography using 55-60% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.89(d，1H)，7.78(m，1H)，7.51(m，3H)，7.32(m，1H)，7.18(m，1H)，4.55(s，2H)，3.74(s，3H)。

[0554]Example 63

[0555]2- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -pyridine

[0556]From 3-chloromethyl-5-m-tolyl- [1, 2, 4 ]Oxadiazole (20.8mg, 0.1mmol) was reacted with pyridine-2-thiol (12.2mg, 0.11mmol) and potassium carbonate in DMF (0.8ml) at room temperature for 15 h to give 2- (5-m-tolyl- [1, 2, 4)]Oxadiazol-3-ylmethylthio) -pyridine (27.3mg, 96.5%). Purification was achieved via flash chromatography on silica gel using 20% ethyl acetate in hexanes.¹HNMR(CDCl₃)，δ(ppm)：8.47(dd，1H)，7.94(s，1H)，7.90(t，1H)，7.51(dt，1H)，7.38(d，2H)，7.26(dd，1H)，7.02(dd，1H)，4.61(s，2H)，2.42(s，3H)。

[0557]Example 64

[0558]2- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1H-imidazo [4, 5-b ] pyridine

[0559]From 3-chloromethyl-5- (3-methoxy-phenyl) - [1, 2, 4]]Oxadiazole (51.2mg, 0.25mmol), 1H-imidazo [4, 5-b]Pyridine-2-thiol (37.5mg, 0.23mmol) and potassium carbonate (80mg, 0.58mmol) in DMF (1.5ml) at room temperature overnight to give 2- [5- (3-methoxy-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethylthio]-1H-imidazo [4, 5-b]Pyridine (74.5mg, 96%). Purification was achieved on silica gel using 25-50% ethyl acetate in dichloromethane.¹H NMR(CDCl₃)，δ(ppm)：8.24(br s，1H)5 7.88 br s，1H)，7.66(d，1H)，7.55(m，3H)，7.29(d，1H)，7.19(m，1H)，4.82(s，2H)，3.85(s，3H)。

[0560]Example 65

[0561]5- (3-fluoro-5-methyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0562]In acetonitrile (1ml) at room temperature, from 3-chloromethyl-5- (3-fluoro-5-methyl-phenyl) - [1, 2, 4-]Oxadiazole (50mg, 0.22mmol), Potassium carbonate (91.5mg, 0.66mmol) and 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4 ]Triazole-3-thiol (52.2mg, 0.26mmol) gives 5- (3-fluoro-5-methyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazole (58mg, 68%, white solid). Purification was achieved by SPE (flash) chromatography using 40-100% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.70(s，1H)，7.58(d，1H)，7.52(m，1H)，7.49(m，1H)，7.18(m，1H)，7.12(d，1H)，4.53(s，2H)，3.73(s，3H)，2.42(s，3H)。

[O563]Example 66

[0564] 3-methyl-5- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine

[0565]In acetonitrile (1ml) at room temperature, from 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (26mg, 0.13mmol), 3- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -5-methyl-pyridine (25mg, 0.12mmol) and potassium carbonate (50mg, 0.36mmol) to give 3-methyl-5- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]Pyridine (19.0mg, 43%, pale yellow solid). Purification was achieved via SPE (flash) chromatography using 100% ethyl acetate.¹H NMR(CDCl₃)，δ(ppm)：9.13(s，1H)，8.65(s，1H)，8.16(s，1H)，7.50(m，2H)，7.19(t，1H)4.57(s，2H)3.74(s，3H)，2.43(s，3H)。

[0566]Example 67

[0567]3- (4-methyl-5-phenyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole

[0568] From 3-chloromethyl-5-m-tolyl- [1, 2, 4] oxadiazole (48.4mg, 0.23mmol), potassium carbonate (96mg, 0.70mmol), 4-methyl-5-phenyl-4H- [1, 2, 4] triazole-3-thiol (44.4mg, 0.23mmol) in acetonitrile (2ml) at 60 ℃ overnight, 3- (4-methyl-5-phenyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole (55.8mg, 67%, white solid) was obtained. Purification was achieved on silica gel using 50% ethyl acetate in hexanes. δ (ppm): 7.89(m, 2H), 7.64(m, 2H), 7.50(m, 3H), 7.39(m, 2H), 4.56(s, 2H), 3.61(s, 3H), 2.41(s, 3H).

[0569]Example 68

[0570]2- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine

[0571]From 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (48.4mg, 0.23mmol), Potassium carbonate (96mg, 0.70mmol) and 4-methyl-5-pyridin-2-yl-4H- [1, 2, 4]Triazole-3-thiol (44.6mg, 0.23mmol) in acetonitrile (2ml) at 60 ℃ overnight to give 2- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4)]Oxadiazol-3-ylmethylthio) -4H- [1, 2, 4]Triazol-3-yl]Pyridine (42.8mg, 51%, off-white solid). Purification was achieved on silica gel using 50% ethyl acetate in hexanes.¹HNMR(CDCl₃)，δ(ppm)：8.62(d，1H)，8.30(d，1H)，7.85(m，3H)，7.36(m，3H)，4.59(s，2H)，4.02(s，3H)，2.40(s，3H)。

[0572]Example 69

[0573] 4-benzyl-2- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -morpholine

[0574]From 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (59.9mg, 0.29mmol), Potassium carbonate (119mg, 0.86mmol) and 5- (4-benzyl-morpholin-2-yl) -4-methyl-4H- [1, 2, 4]Triazole-3-thiol (83.3mg, 0.29mmol) in acetonitrile (2ml) at 60 ℃ overnight to give 4-benzyl-2- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4)]Oxadiazol-3-ylmethylthio) -4H- [1, 2, 4]Triazol-3-yl]Morpholine (95.8mg, 83%, clear oil). Purification was achieved on silica gel using ethyl acetate with 10% methanol. ¹H NMR(CDCl₃)，δ(ppm)：7.88(m，2H)，7.31(m，7H)，4.75(dd，1H)，4.47(dd，2H)，3.84(m，2H)，3.59(bs，5H)，3.20(d，1H)，2.72(m，2H)，2.43(s，3H)，2.30(dt，1H)。

[0575]Example 70

[0576]4- [ 4-methyl-5- (5-thiophen-3-yl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine

[0577]3-chloromethyl-5-thiophen-3-yl- [1, 2, 4]Oxadiazole (40mg, 0.20mmol), Potassium carbonate (82.5mg, 0.60mmol) and 4-methyl-5-pyridin-4-yl-4H- [1, 2, 4]Triazole-3-thiol (38.3mg, 0.20mmol) in acetonitrile (2ml) at 60 ℃ overnight to give 4- [ 4-methyl-5- (5-thiophen-3-yl- [1, 2, 4)]Oxadiazol-3-ylmethylthio) -4H- [1, 2, 4]Triazol-3-yl]Pyridine (24mg, 34%, white solid). Purification was achieved on silica gel using ethyl acetate with 10% methanol.¹HNMR(CDCl₃)，δ(ppm)：8.80(bs，2H)，8.20(dd，1H)，7.62(m，3H)，7.45(dd，1H)，4.59(s，2H)，3.70(s，3H)。

[0578]Example 71

[0579]3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-thiazol-4-yl- [1, 2, 4] oxadiazole

[0580]In acetonitrile (1ml) at room temperature, from 3-chloromethyl-5-thiophen-2-yl- [1, 2, 4]Oxadiazole (37mg, 0.18mmol), Potassium carbonate (75.3mg, 0.54mmol) and 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (43mg, 0.22mmol) gives 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-thiazol-4-yl- [1, 2, 4]Oxadiazole (44mg, 67%, white solid). Purification was achieved by SPE (flash) chromatography using 50-100% ethyl acetate in hexanes. ¹H NMR(DMSO)，δ(ppm)：9.37(d，1H)，8.86(d，1H)，7.80(d，1H)，7.65(d，1H)，7.26(t，1H)，4.54(s，2H)，3.75(s，3H)。

[0581]Example 72

[0582]3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-nitro-phenyl) - [1, 2, 4] oxadiazole

[0583]In acetonitrile (2ml) at room temperature, from 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (91mg, 0.46mmol), 3-chloromethyl-5- (3-nitro-phenyl) - [1, 2, 4%]Oxadiazole (100mg, 0.42mmol) and potassium carbonate (173mg, 1.25mmol) gave 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (3-nitro-phenyl) - [1, 2, 4]Oxadiazole (21.1mg, 13%, white solid). Purification was achieved via SPE (flash) chromatography using 60% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：8.96(s，1H)，8.44(t，2H)，7.75(t，1H)，7.51(m，2H)，7.19(t，1H)，4.59(s，2H)，3.76(s，3H)。

[0584]Example 73

[0585] 2-methyl-4- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine

[0586]In acetonitrile (1ml) at room temperature, from 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (51mg, 0.26mmol), 4- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -2-methyl-pyridine (50mg, 0.24mmol) and potassium carbonate (100mg, 0.72mmol) to give 2-methyl-4- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]Pyridine (59.2mg, 66%, white solid). Purification was achieved via SPE (flash) chromatography using 100% ethyl acetate. ¹H NMR(DMSO)，δ(ppm)：8.71(d，1H)，7.79(s，1H)，7.73(d，1H)，7.49(m，2H)，7.19(t，1H)，4.58(s，2H)，3.73(s，3H)，2.65(s，3H)。

[0587]Example 74

[0588]3- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine

[0589]From 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (50mg, 0.24mmol), Potassium carbonate (100mg, 0.72mmol) and 4-methyl-5-pyridin-3-yl-4H- [1, 2, 4]Triazole-3-thiol (46.1mg, 0.24mmol) in acetonitrile (2ml) at 60 deg.C overnight to give 3- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4)]Oxadiazol-3-ylmethylthio) -4H- [1, 2, 4]Triazol-3-yl]Pyridine (30mg, off-white solid). Purification was achieved on silica gel using ethyl acetate with 5% methanol.¹HNMR(CDCl₃)，δ(ppm)：8.90(bs，1H)，8.76(bs，1H)，8.03(m，1H)，7.88(m，2H)，7.46(dd，1H)，7.40(m，2H)，4.58(s，2H)，3.66(s，3H)，2.42(s，3H)。

[0590]Example 75

[0591]3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole

[0592]From 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (50mg, 0.24mmol), Potassium carbonate (100mg, 0.72mmol) and 4-methyl-5-thiophen-3-yl-4H- [1, 2, 4]Triazole-3-thiol (47.3mg, 0.24mmol) in acetonitrile (2ml) at 60 ℃ overnight to give 3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (60mg, white solid). Purification was achieved on silica gel using 40% ethyl acetate in dichloromethane. ¹HNMR(CDCl₃)，δ(ppm)：7.87(m，2H)，7.71(dd，1H)，7.48(m，2H)，7.38(m，2H)，4.52(s，2H)，3.67(s，3H)，2.41(s，3H)。

[0596]Example 76

[0594]3- (4-methyl-5-thiazol-4-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole

[0595]From 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (50mg, 0.24mmol), Potassium carbonate (100mg, 0.72mmol) and 4-methyl-5-thiazol-4-yl-4H- [1, 2, 4]Triazole-3-thiol (47.5mg, 0.24mmol) in acetonitrile (2ml) at 60 ℃ overnight to give 3- (4-methyl-5-thiazole-4-yl-4H- [1, 2, 4]]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (30mg, off-white solid). Purification was achieved on silica gel using 60% ethyl acetate in dichloromethane.¹HNMR(CDCl₃)，δ(ppm)：8.89(d，1H)，8.22(d，1H)，7.88(m，2H)，7.38(m，2H)，4.55(s，2H)，3.94(s，3H)，2.41(s，3H)。

[0596]Example 77

[0597]5- (3-iodo-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0598]In acetonitrile (10ml) at room temperature, the reaction mixture was purified from 3-chloromethyl-5- (3-iodo-phenyl) - [1, 2, 4]]Oxadiazole (500mg, 1.56mmol), Potassium carbonate (647mg, 4.68mmol) and 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (369mg, 1.87mmol) gives 5- (3-iodo-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazole (725mg, 97%, white solid). Purification was achieved via flash column chromatography using 40% ethyl acetate in hexanes. ¹H NMR(CDCl₃)，δ(ppm)：8.44(d，1H)，8.06(d，1H)，7.93(d，1H)，7.51(m，2H)，7.26(t，1H)，7.19(m，1H)，4.54(s，2H)，3.73(s，3H)。

[0599]Example 78

[0600]5- (3-ethyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0601]In acetonitrile (1ml) at room temperature, from 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (59mg, 0.30mmol), 3-chloromethyl-5- (3-ethyl-phenyl) - [1, 2, 4%]Oxadiazole (60mg, 0.27mmol) and potassium carbonate (111mg, 0.80mmol) gave 5- (3-ethyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazole (28.1mg, 27%, white solid). Purification was achieved via SPE (flash) chromatography using 50% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.90(t，2H)，7.51(m，2H)，7.42(t，2H)，7.18(m，1H)，4.52(s，2H)，3.72(s，3H)，2.70(m，2H)，1.26(t，3H)。

[0602]Example 79

[0603]2- [5- (2-methyl-pyridin-4-yl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1H-benzimidazole

[0604]In DMF (1ml) at room temperature, the mixture was prepared from 2-mercaptobenzimidazole 2- (41mg, 0.27mmol) and 4- (3-chloromethyl- [1, 2, 4%]Oxadiazol-5-yl) -2-methyl-pyridine (50mg, 0.24mmol) and potassium carbonate (100mg, 0.72mmol) to give 2- [5- (2-methyl-pyridin-4-yl) - [1, 2, 4]Oxadiazol-3-ylmethylthio]-1H-benzimidazole (46.0mg, 59%, white solid). Purification was achieved via SPE (flash) chromatography using 100% ethyl acetate and trituration with ether. ¹H NMR(DMSO-d₆，δ(ppm)：8.72(d，1H)，7.87(s，1H)，7.78(d，1H)，7.47(t，2H)，7.14(m，2H)，4.81(s，2H)，2.59(s，3H)。

[0605]Example 80

[0606]2- [5- (3-iodo-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1H-benzimidazole

[0607]In DMF (1ml) at room temperature, from 3-chloromethyl-5- (3-iodo-phenyl) - [1, 2, 4]]Oxadiazole (50mg, 0.16mmol), Potassium carbonate (65mg, 0.47mmol) and 1H-benzimidazole-2-thiol (23mg, 0.16mmol) gave 2- [5- (3-iodo-phenyl) - [1, 2, 4] methyl ethyl ester]Oxadiazol-3-ylmethylthio]-1H-benzimidazole (36mg, 51%, white solid). Purification was achieved by SPE (flash) chromatography using 50-100% ethyl acetate in hexanes followed by ethyl acetate trituration.¹H NMR(DMSO)，δ(ppm)：12.73(bs，1H)，8.30(s，1H)，8.09(d，2H)，7.45(m，3H)，7.18(m，2H)，4.78(s，2H)。

06081 example 81

[0609]3- (4-methyl-5-trifluoromethyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole

[0610]From 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (40mg, 0.19mmol), Potassium carbonate (79mg, 0.58mmol) and 4-methyl-5-trifluoromethyl-4H- [1, 2, 4]Triazole-3-thiol (35.1mg, 0.19mmol) in acetonitrile (2ml) at 60 ℃ overnight to give 3- (4-methyl-5-trifluoromethyl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (54.3mg, 80%, clear oil). Purification was achieved from silica gel using 50% ethyl acetate in hexanes.¹HNMR(CDCl₃)，δ(ppm)：7.87(m，2H)，7.41(m，2H)，4.59(s，2H)，3.69(s，3H)，2.43(s，3H)。

[0611]Example 82

[0612]2, 6-dichloro-4- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4] oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4] triazol-3-yl ] -pyridine

[0613]From 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (40mg, 0.19mmol), Potassium carbonate (79mg, 0.58mmol) and 5- (2, 6-dichloro-pyridin-4-yl) -4-methyl-4H-1, 2, 4]Triazole-3-thiol (50.1mg, 0.19mmol) in acetonitrile (2ml) at 60 ℃ overnight to give 2, 6-dichloro-4- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4)]Oxadiazol-3-ylmethylthio) -4H- [1, 2, 4]Triazol-3-yl]Pyridine (51.4mg, 62%, off-white solid). Purification was achieved from silica gel using 80% ethyl acetate in hexanes.¹H NMR(CDCl₃)，δ(ppm)：7.87(m，2H)，7.61(s，2H)，7.40(m，2H)，4.60(s，2H)，3.71(s，3H)，2.42(s，3H)。

[0614]Example 83

[0615]3- (4-methyl-5-p-tolyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole

[0616]From 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (40mg, 0.19mmol), Potassium carbonate (79mg, 0.58mmol), 4-methyl-5-p-tolyl-4H- [1, 2, 4]Triazole-3-thiol (39.4mg, 0.19mmol) in acetonitrile (2ml) at 60 ℃ overnight to giveTo 3- (4-methyl-5-p-tolyl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (57.8mg, 81%, off-white solid). Purification was achieved from silica gel using 80% ethyl acetate in hexanes. ¹HNMR(CDCl₃)，δ(ppm)：7.88(m，2H)，7.53(d，2H)，7.39(m，2H)，7.30(d，2H)，4.55(s，2H)，3.59(s，3H)，2.42(d，6H)。

[0617]Example 84

[0618] Dimethyl- {3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] phenyl } -amine

[0619]In acetonitrile (1ml) at room temperature, from 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (18mg, 0.093mmol), 3- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -phenyl]-dimethyl-amine (20mg, 0.084mmol) and potassium carbonate (35mg, 0.25mmol) to give dimethyl- {3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]Phenyl } -amine (28.0mg, 85%, white solid). Purification was achieved via SPE (flash) chromatography using hexane with 70% ethyl acetate.¹H NMR(CDCl₃)，δ(ppm)：7.49(m，2H)，7.36(m，3H)，7.17(t，1H)，6.91(d，1H)，4.51(s，2H)，3.72(s，3H)，3.00(s，6H)。

[0620]Example 85

[0621]5- (3-chloro-phenyl) -3- (4-methyl-5-thiophene) -2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0622]In acetonitrile (1ml) at room temperature, from 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (47mg, 0.24mmol), 3-chloromethyl-5- (3-chloro-phenyl) - [1, 2, 4%]Oxadiazole (50mg, 0.22mmol) and potassium carbonate (91mg, 0.66mmol) gave 5- (3-chloro-phenyl) -3- (4-methyl-5-thiophen) -2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazole (76.8mg, 90%, white solid). Hexane with 70% ethyl acetate, via SPE (flash) chromatography And (5) realizing purification.¹H NMR(CDCl₃)，δ(ppm)：8.09(s，1H)，7.98(d，1H)，7.49(m，4H)，7.18(m，1H)，4.55(s，2H)，3.73(s，3H)。

[0623]Example 86

[0624]3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (3-trifluoromethoxyphenyl) [1, 2, 4] oxadiazole

[0625]3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]]Triazol-3-ylsulfanylmethyl) -5- (3-trifluoromethoxy-phenyl) [1, 2, 4]Oxadiazole (144.0mg, 91%, white solid) was prepared from 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (78mg, 0.39mmol), 3-chloromethyl 5- (3-trifluoromethoxy-phenyl) - [1, 2, 4]]Oxadiazole (100mg, 0.36mmol) and potassium carbonate (149mg, 1.08mmol) were reacted in acetonitrile (2ml) at room temperature. Purification was performed by SPE (flash) chromatography using 55% ethyl acetate in hexane.¹HNMR(CDCl₃)，δ(ppm)：8.04(d，1H)，7.95(s，1H)，7.51(m，4H)，7.18(m，1H)，4.56(s，2H)，3.74(s，3H)

[0626]Example 87

[0627]3- (5-cyclohexane-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole

[0628]3- (5-cyclohexane-4-methyl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (10.5mg, clear oil) was prepared from 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (50mg, 0.24mmol), Potassium carbonate (165mg, 1.20mmol), 5-cyclohexane 4-methyl-4H- [1, 2, 4]Triazole-3-thiol (94.6mg, 0.48mmol) was obtained in acetonitrile (3ml) at 60 ℃ overnight. The purification was carried out on silica gel with a 2% ammonia (2N methanol) in dichloromethane. ¹HNMR(CDCl₃)，δ(ppm)：7.88(m，2H)，7.39(m，2H)，4.42(s，2H)，3.46(s，3H)，2.60(m，1H)，2.42(d，3H)，1.74(m，7H)，1.34(m，3H)。

[0629]Example 88

[0630]3- (5-tert-butyl-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole

[0631]3- (5-tert-butyryl-4-methyl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (56.8mg, white solid) was prepared from 3-chloromethyl-5-m-tolyl- [1, 2, 4]Oxadiazole (50mg, 0.24mmol), Potassium carbonate (100mg, 0.72mmol), 5-tert-butyl-4-methyl-4H- [1, 2, 4]Triazole-3-thiol (41mg, 0.24mmol) was obtained in acetonitrile (2ml) at 60 ℃ overnight. The purification was carried out on silica gel using a hexane solution containing 80% ethyl acetate.¹HNMR(CDCl₃)，δ(ppm)：7.89(m，2H)，7.40(m，2H)，4.46(s，2H)，3.63(s，3H)，2.43(m，3H)，1.45(s，9H)。

[0632]Example 89

[0633]5- (3-bromo-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0634]5- (3-bromo-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazole (83.4mg, 86%, white solid) was prepared from 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (47mg, 0.24mmol), 5- (3-bromo-phenyl) -3-chloromethyl [1, 2, 4]Oxadiazole (60mg, 0.22mmol), potassium carbonate (91mg, 0.66mmol) in acetonitrile (2ml) was obtained at room temperature. Purification was performed by SPE (flash) chromatography using 60% ethyl acetate in hexane. ¹HNMR(CDCl₃)，δ(ppm)：8.25(t，1H)，8.02(d，1H)，7.73(d，1H)，7.50(m，2H)，7.40(t，1H)，7.19(m，1H)，4.55(s，2H)，3.73(s，3H)

[0635] Example 90

[0636]2- [5- (3-bromobenzene-yl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1H-benzimidazole

[0637]2- [5- (3-bromo-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethylthio]-1H-benzimidazole (71.1mg, 84%, white solid) was prepared from 2-mercaptobenzimidazole (35mg, 0.23mmol), 5- (3-bromo-phenyl) -3-chloromethyl [1, 2, 4%]Oxadiazole (60mg, 0.22mmol) and potassium carbonate (91mg, 0.66 mmol) were reacted in DMF (2ml) at room temperature. Purification was performed by SPE (flash) chromatography using 35% ethyl acetate in hexane and trituration with ether.¹HNMR(DMSO-d₆，δ(ppm)：12.78 broad s，1H)，8.18(s，1H)，8.07(d，1H)，7.93(d，1H)，7.59(t，1H)，7.46(s，2H)，7.14(m，2H)，4.77(s，2H)

[0638] Example 91

[0639]5- (3-methoxymethyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0640]5- (3-methoxymethyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazole (76mg, 90%, white solid) was prepared from 3-chloromethyl-5- (3-methoxymethyl-phenyl) - [1, 2, 4%]Oxadiazole (50mg, 0.21mmol), Potassium carbonate (87mg, 0.63mmol), 4-methyl 5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (50mg, 0.25mmol) was obtained in acetonitrile (2ml) at room temperature. Purification was performed by SPE (flash) chromatography using 40-70% ethyl acetate in hexane. ¹HNMR(CDCl₃)，δ(ppm)：8.06(s，1H)，8.01(d，1H)，7.59(d，1H)，7.50(m，3H)，7.18(t，1H)，4.54(s，2H)，4.50(s，2H)，3.72(s，3H)，3.43(s，3H)。

[0641]Example 92

[0642]2- [5- (3-methoxymethyl-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1H-benzimidazole

[0643]2- [5- (3-methoxymethyl-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethylthio]-1H-benzimidazole (62mg, 84%, white solid) was prepared by reacting 3-chloromethyl-5- (3-methoxymethyl-phenyl) - [1, 2, 4]]Oxadiazole (50mg, 0.21mmol), Potassium carbonate (87mg, 0.63mmol), 1H-benzimidazole-2-SulfurAlcohol (32mg, 0.21mmol) was reacted in DMF (2ml) at room temperature. Purification was performed by SPE (flash) chromatography using 40-100% ethyl acetate in hexane.¹HNMR(DMSO)，δ(ppm)：8.09(d，2H)，7.59(m，2H)，7.46(bs，2H)，7.14(m，2H)，4.77(s，2H)，4.51(s，2H)，3.35(s，3H)。

[0644] Example 93

[0645]4- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -pyridine

[0646]A solution of isonicotinoyl chloride (2.0g, 11.2mmol) in dichloromethane was treated with 2-chloro-N-hydroxy-acetamidine (1.58g, 14.6mmol) and triethylamine (4.67ml, 33.6mmol) was added dropwise. After stirring at room temperature for 1 hour, extraction with ethyl acetate and washing with water and brine gave the oxo-acyl intermediate (150 mg, 0.7mmol, used without further purification). The crude product in acetonitrile (2ml) and DMSO (2ml) was added K₂CO₃(292mg, 2.1mmol) and 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4 ]Triazole-3-thiol (140mg, 0.7mmol) was stirred at room temperature for 24 hours, followed by stirring at 120 ℃ for 1.5 hours (sealed tube). Work-up with ethyl acetate standard water and washing with water and brine before chromatography on silica gel gave the title compound (110mg, 44%).¹HNMR(CDCl₃，δ(ppm)：8.41 dd，2H)，7.92(dd，2H)，7.50(dd，1H)，7.47(dd，1H)，7.18(dd，1H)，4.58(s，2H)，3.74(s，3H)；LC-MS(M+H)⁺：357。

[0647] EXAMPLE 94 preparation of a procedure similar to that of example 93

[0648]Example 94

[0649]4- [5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-3-yl ] -pyridine

[0650]4- [5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-3-yl]Pyridine (12mg, 5%) from N-hydroxy-isonicotinamidine (b200mg, 1.4mmol) and chloroacetyl chloride (0.11ml, 1.4mmol) and triethylamine (0.5ml, 3.5 mmol); work-up with water gave intermediate (150mg, 0.7 mmol); by K₂CO₃(292mg, 2.1mmol), and 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (140mg, 0.7 mmol). The purification process was carried out by silica gel chromatography and recrystallization.¹HNMR(CDCl₃)，δ(ppm)：8.76(dd，2H)，7.89(dd，2H)，7.53(dd，1H)，7.48(dd，1H)，7.18(dd，1H)，4.71(s，2H)，3.73(s，3H)；LC-MS(M+H)⁺：357。

[0651]Example 95

[0652]2- {1- [5- (3-methoxyphenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -1-methyl-1H-imidazo [4, 5-b ] pyridine and 2- [5- (3-methoxy-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -1-methyl-1H-imidazo [4, 5-b ] pyridine

[0653]THF (3ml) was added to sodium hydride (60%, 8mg, 0.2mmol) and 2- [5- (3-methoxy-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethylthio]-1H-imidazo [4, 5-b]Pyridine (24.6mg, 0.072mmol) and the resulting mixture stirred at 0 ℃ for about 15 minutes. Methyl iodide (20. mu.L, 0.32mmol) was added to the resulting mixture and stirred at 0 ℃ for 2 hours. The reaction was quenched by the addition of dichloromethane (10ml) and water (2 ml). After vigorous stirring, the organic extract (10ml, plus 3X 5ml) was eluted through a Chem Elut extraction column (Varian, cat # 1219-. Purification was carried out by SPE chromatography (5g silica) using ethyl acetate/dichloromethane/hexane solutions 25/25/50 to 50/25/25 to give two products. The first product eluted was 2- {1- [5- (3-methoxyphenyl) - [1, 2, 4]]Oxadiazol-3-yl]-ethylthio } -1-methyl-1H-imidazo [4, 5-b]Pyridine (6mg, 23%).¹HNMR(CDCl₃)，δ(ppm)：8.46(d，1H)，7.72(d，1H)，7.62(d，1H)，7.55(d，1H)，7.42(t，1H)，7.14(m，2H)，5.67(q，1H)，3.88(s，3H)，3.71(s，3H)，2.01(d，3H)。

[0654]The second product eluted is 2- [5- (3-methoxy-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethylthio]-1-methyl-1H-imidazo [4, 5-b]Pyridine (12mg, 47%).¹HNMR(CDCl₃)，δ(ppm)：8.44(d，1H)，7.69(d，1H)，7.60(d，1H)，7.55(d，1H)，7.41(t，1H)，7.13(m，1H)，4.90(s，2H)，3.87(s，3H)，3.70(s，3H)。

[0655] EXAMPLES 96-97 were prepared in a similar manner to the procedure set forth in example 95.

[0656]Example 96

[0657]3- [ 1-methyl-1- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole

[0658]3- [ 1-methyl-1- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]]Triazol-3-ylthio) -ethyl]-5-m-tolyl- [1, 2, 4]Oxadiazole (13mg, 47%) was prepared from 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4%]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (25.5mg, 0.069mmol) and 60% sodium hydride (37mg, 0.92mmol) and iodomethane (0.10ml, 1.6mmol) were reacted in THF (3ml) at room temperature for 2 h. The product was extracted with ethyl acetate and purified on a SPE with a 1: 1 dichloromethane: hexane solution containing 20-40% ethyl acetate.¹HNMR(CDCl₃)，δ(ppm)：7.83(br s，2H)，7.48(d，1H)，7.42(d，1H)，7.36(m，2H)，7.13(m，1H)，3.50(s，3H)，2.35(s，3H)，1.95(s，6H)。

[0659]Example 97

[0660]3- [1- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylthio) -ethyl ] -5-m-tolyl- [1, 2, 4] oxadiazole

[0661]3- [1- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]]Triazol-3-ylthio) -ethyl]-5-m-tolyl- [1, 2, 4]Oxadiazole (6.1mg, 17%) was prepared from 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4%]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (33.8mg, 0.091mmol) and 60% sodium hydride (17mg, 0.42mmol) and iodomethane (20. mu.L, 0.32mmol) in THF (2.5 mL)) And reacted at room temperature for 1 hour. The product was extracted with dichloromethane and purified on a SPE with a 1: 1 chloroform: hexane solution containing 25-40% ethyl acetate. ¹HNMR(CDCl₃)，δ(ppm)：7.89(br s，2H)，7.50(d，1H)，7.46(d，1H)，7.38(m，2H)，7.16(m，1H)，4.89(q，1H)，3.64(s，3H)，2.37(s，3H)，1.90(d，3H)。

[0662] Example 98

[0663]3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole-3-sulfonylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole and 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazole-3-sulfinylmethyl) -5-m-tolyl- [1, 2, 4] oxadiazole

[0664]Dichloromethane (2.5ml) was added to 3-chloro-perbenzoic acid (57-85%, 49.5mg, 0.16-0.25mmol) and 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4%]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (45mg, 0.12mmol) and the resulting mixture was stirred at room temperature overnight. The reaction was quenched by the addition of dichloromethane (10ml) and 1M sodium hydroxide (3 ml). After vigorous stirring, the organic extract (10ml, plus 3X 5ml) was extracted through a Chem Elut extraction column (Varian, cat # 1219-. Purification was performed by SPE chromatography (5g silica) using a 1: 1 dichloromethane: hexane solution containing 10-30% ethyl acetate to give two products. The first product eluted is 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]]Triazole-3-sulfonylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (12.3mg, 25%).¹HNMR(CDCl₃)，δ(ppm)：7.83(br s，2H)，7.63(d，1H)，7.56(d，1H)，7.36(m，2H)，7.24(m，1H)，5.12(s，2H)，3.94(s，3H)，2.36(d，3H)。

[0665]The second product eluted is 3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4) ]Triazole-3-sulfinylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazole (33.2mg, 71%).¹HNMR(CDCl₃)，δ(ppm)：7.87(br s，2H)，7.59(d，1H)，7.54(d，1H)，7.38(m，2H)，7.22(m，1H)，5.05(d_AB，1H)，4.90(d_AB，1H)，4.03(s，3H)，2.39(d，3H)。

[0666]Example 99

[0667]5- (3-furan-3-yl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0668]In the presence of 5- (3-iodo-phenyl) -3- (4-methyl-5-thiophen-2-yl 4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]A vial of oxadiazole (50mg, 0.10mmol) was charged with 3-furanboronic acid (17mg, 0.16mmol), tetrakis (triphenylphosphine) palladium (0) (6mg, 0.0052mmol), ethylene glycol dimethyl ether (1ml) and 2M sodium carbonate (1 ml). The vial was sealed and heated to 90 ℃ with vigorous stirring for 1 hour. The reaction was cooled, diluted with ethyl acetate, washed with water and saturated brine, filtered and concentrated. The residue was purified by flash column chromatography using a hexane solution containing 70% ethyl acetate. Trituration of the further purified product with a mixture of diethyl ether and hexane afforded 25mg (57%) of the title compound as a tan solid after filtration.¹HNMR(CDCl₃)，δ(ppm)：8.18(s，1H)，7.98(d，1H)，7.79(s，1H)，7.71(d，1H)，7.51(m，4H)，7.17(m，1H)，6.74(s，1H)，4.55(s，2H)，3.73(s，3H)。

[0669] Intermediate product

[0670]Example 100

[0671] Pyrimidine-4-carboxylic acid.

[0672]3-methylpyrimidine (9.41g, 100mmol), potassium permanganate (26.9g) and sodium carbonate (10.6g) were heated under reflux in water (100ml) for 72 hours, then filtered through celite. The filtrate was washed with DCM and EtOAc several times and acidified by addition of concentrated hydrochloric acid. The precipitate formed was collected and washed with water to give 1.37g of a white solid, i.e. the title compound. ¹HNMR(DMSO-d6)δ(ppm)：13.94(br s，1H)，9.37(d，1H)，9.07(d，1H)，8.01(dd，1H)。

[0673]Example 101

[0674] 5-chloro-thiophene-3-carboxylic acid.

[0675]Thiophene-3-carboxylic acid (17.51g, 136.6mmol) and 1-chloro-pyrrolidine-2, 5-dione (23.7g) were poured into water (700ml) after refluxing in acetic acid (200ml) under argon for 4 hours. Repeated extraction with DCM in small amount, back extraction with 2M sodium hydroxide solution in small amount from the combined organic matter, washing the combined alkaline water solution with DCM, and acidifying and precipitating with concentrated hydrochloric acid to obtain crude product. The precipitate was recrystallized from water to yield 14.98g of precipitated crystals by MS and¹H-NMR measurement of the title compound as a grey solid containing approximately 20 mol% of dichloroated by-products.¹HNMR(DMSO-d6)δ(ppm)：8.15(d，1H)，7.37(d，1H)。

[0676] Example 102

[0677] 3-methylsulfanyl-benzoic acid

[0678]Methyl iodide (0.972mL) was added to a mixture of 3-mercapto-benzoic acid (601mg, 3.9mmol) and potassium carbonate (2.7g, 19.5mmol) in DMF (8mL) while cooling on ice. After the reaction was warmed to room temperature and stirred for 1 hour, the reaction mixture was diluted with ethyl acetate, washed with water (3X), dried over anhydrous sodium sulfate, filtered, and concentrated to give methyl 3-methylsulfanyl-benzoate (684mg, 96%, yellow oil).¹HNMR(CDCl₃)，δ(ppm)：7.90(s，1H)，7.80(d，1H)，7.44(d，1H)，7.35(t，1H)，3.92(s，3H)，2.53(s，3H)。

[0679]A mixture of methyl 3-methylthiobenzoate (684mg, 3.8mmol) and 1N NaOH (5.6mL, 5.6mmol) in methanol (8mL) and THF (8mL) was heated to 70 ℃ for 1 h. The reaction mixture was concentrated and the resulting residue was diluted with water. Acidification to pH-2 was done by addition of 1N HCl, the aqueous layer was extracted with ethyl acetate and washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 3-methylsulfanyl-benzoic acid (616mg, 97%, white solid). ¹HNMR(DMSO)，δ(ppm)：13.1(bs，1H)，7.76(s，1H)，7.70(d，1H)，7.51(d，1H)，7.44(t，1H)，2.52(s，3H)。

[0680]Example 103

[0681] 3-cyclopropyl-benzoic acid

[0682] 1.0M diethylzinc (27.3ml, 27.3mmol) in hexane was added to a solution of 2, 4, 6-trichlorophenol (5.4g, 27.3mmol) in dichloromethane (100ml) at-40 ℃. After stirring for 15 minutes, diiodomethane (2.2mL, 27.3mmol) was added at 40 ℃ and stirred for an additional 15 minutes. 1-bromo-3-ethenyl-benzene (2.5g, 13.7mmol) was then added to the reaction mixture, warmed to room temperature and stirred overnight. The reaction mixture was diluted with dichloromethane, washed with IN HCl (2 ×), saturated sodium bicarbonate (2 ×), saturated sodium sulfite, 1N sodium hydroxide and saturated brine, dried over magnesium sulfate, filtered and concentrated. GC-MS showed the reaction mixture to contain 1-bromo-3-cyclopropyl-benzene and 1-bromo-3-alkenylbenzene.

[0683] To remove the bromo-3-alkenylbenzene, the crude mixture was reacted with potassium permanganate. A potassium permanganate/water (1.5g/20mL) solution was added dropwise to a solution of the crude mixture (. about.3.5 g) in THF (40mL) at 0 deg.C and then warmed to room temperature. After 1 hour, the reaction mixture was diluted with diethyl ether, washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. Purification procedure on flash column chromatography eluting with 100 hexanes yielded 1-bromo-3-cyclopropyl-benzene 2.20g, 81%).

[0684]1.6M n-butyllithium in hexane (3.2mL, 5.1mmol) was added dropwise to the 1-bromo-3-cyclopropyl-benzene solution at-78 deg.C and stirred for 1 hour. The reaction mixture was transferred via a catheter into a 250mL round bottom flask equipped with a stir bar, which had approximately 1/4 full of dry ice, and then stirred for 1 hour. The reaction mixture was concentrated and the resulting residue was diluted with water. The aqueous layer was washed with dichloromethane (3 ×), acidified to pH-2 with 1N HCl, and extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 3-cyclopropyl-benzoic acid (356mg, 43%, white solid).¹HNMR(DMSO)，δ(ppm)：12.90(bs，1H)，7.71(d，1H)，7.64(s，1H)，7.34(m，2H)，2.01(m，1H)，0.99(m，2H)，0.70(m，2H)。

[0685]Example 104

[0686] 3-tert-Butoxycarbonylamino-benzoic acid

[0687] In a flask charged with ethyl-3-aminobenzoate (1g, 6.05mmol), di-tert-butyl carbonate (3.16g, 14.5mmol), triethylamine (500mg, 4.94mmol) and THF (10mL) were added, and the mixture was stirred at 60 ℃ for 2 hours, then at room temperature overnight. The THF was removed in vacuo and the crude ester was partitioned between ethyl acetate and water, washed with saturated brine, dried over anhydrous sodium sulfate and the solvent removed in vacuo. The product was purified by flash column chromatography using 15% ethyl acetate in hexane to give 2g of ethyl 3-tert-butoxycarbonylamino-benzoate (white syrup).

[0688]To the charge of crude 3-tert-butoxycarbonylamino-benzoic acid ethyl ester (. about.2.0 g, 0.00754mmol) was added THF (15mL), and 0.5MLiOH (15 mL). The mixture was heated at 75 ℃ for 2 hours, cooled and the THF was removed. The precipitate was filtered from the resulting mixture, and the filtrate was transferred to a separatory funnel. The aqueous layer was washed with dichloromethane (3 ×) and acidified to pH-5 with 1M HCl. The product was extracted with ethyl acetate, washed with water, saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. 730mg of 3-tert-butoxycarbonylamino-benzoic acid (white solid) was isolated.¹HNMR(DMSO-d₆)δ(ppm)：9.58(s，1H)，8.16(s，1H)，7.63(d，1H)，7.54(d，1H)，7.37(t，1H)，1.49(s，9H)

[0689]Example 105

[0690] 3-acetyl-benzoic acid

[0691]6M sodium hydroxide (25mL) was added to a solution of 3-acetylbenzonitrile (850mg, 5.82mmol) in methanol (25mL) and heated to 90 ℃ overnight. After concentrating the reaction mixture, the aqueous layer was washed with dichloromethane (2 ×) and acidified to pH-3 with 12M HCl. Extracting the precipitate with ethyl acetate, washing with water and saturated brine, adding anhydrous sodium sulfate, drying, filtering, and concentrating to obtain colorless oily 3-ethylbenzoic acid; 0.800g (92%).¹HNMR(CDCl₃)δ(ppm)：8.70(s，2H)，8.33(d，2H)，8.24(d，2H)，7.64(t，1H)，2.70(s，3H)。

[0692]Example 106

[0693] 2-methyl-isonicotinyl hydrazide

[0694]Dichloromethane (10mL) was slowly added to a mixture of 2-methylnicotinic acid hydrochloride (1.1g, 6.34mmol) and oxalyl chloride (6.95mL, 13.9mmol) under argon while the flask was cooled in ice. Dimethylformamide (2 drops) was added to the reaction and stirred overnight, during which time it was warmed to room temperature. The reaction was concentrated and THF (10mL) was added to the flask and placed in an ice bath. Methanol (5mL) was added to the reaction and stirred for 1 hour. The reaction was concentrated and the residue was taken up in NaHCO ₃Layer separation between (saturated) and EtOAc. The product was extracted three times with EtOAc. The combined organic layers were washed with brine, washed with Na₂SO₄Dried, filtered and concentrated. The purification process yielded a clear oil, the title compound, via a solid extraction tube (20% EtOAc/hexanes).¹HNMR(CDCl₃)，δ(ppm)：8.51(d，1H)，7.57(d，1H)，7.51(d，1H)，3.82(s，3H)，2.50(s，3H)。

[0695]Methyl 2-methylisonicotinate (316.5mg, 2.093mmol) was dissolved in MeOH (7mL) under argon and hydrazine monohydrate 98% (1mL, 20.93mmol) was added. The reaction was stirred at room temperature under argon for 18 hours. The reaction was concentrated to give the title compound as a white solid (271.9mg, 86%).¹HNMR(CDCl₃)，δ(ppm)：8.59(d，1H)，7.50(s，1H)，7.38(d，1H)，3.09(br s，3H)，2.60(s，3H)。

[0696]Example 107

[0697] 5-chloro-2-fluoro-benzoylhydrazines

[0698]Step 1: 5-chloro-2-fluoro-benzoic acid methyl ester: methanol (20ml) was added to a solution of 5-chloro-2-fluoro-benzoyl chloride (1.2g, 6.2mmol) in dichloromethane (10ml) in an ice bath. The reaction mixture was heated to room temperature, stirred for 3 hours and concentrated to give 5-chloro-2-fluoro-benzylAcid methyl ester (1.17g, 100%).¹HNMR(CDCl₃) δ (ppm): 7.93(m, 1H), 7.48(m, 1H), 7.12(m, 1H), 3.96(s, 3H). Step 2: 5-chloro-2-fluoro-benzoyl hydrazine: a mixture of methyl 5-chloro-2-fluoro-benzoate (1.17g, 6.2mmol) and hydrazine monohydrate (0.451ml, 9.3mmol) in ethanol (20ml) was stirred at room temperature overnight. The reaction mixture was concentrated and the resulting residue was triturated with diethyl ether to give 5-chloro-2-fluoro-benzoyl hydrazine (497mg, 42%, white solid). ¹HNMR(DMSO)，δ(ppm)：9.66(bs，1H)，7.58(m，2H)，7.36(m，1H)，4.58(bs，2H)。

[0699] Example 108 was prepared in a similar manner to example 107.

[0700] Example 108

[0701] 3-cyano-benzoyl hydrazine

[0702]A solution of 3-cyano-benzoyl chloride (3g, 18.12mmol) in dichloromethane (5mL) and methanol (20mL) was stirred at room temperature overnight. The solvent was removed on a rotary evaporator to give a white solid (3.76 g).¹HNMR(DMSO)，δ(ppm)：8.33 (m，1H)，8.24(m，1H)，8.14(m，1H)，7.76(m，1H)，3.89(d，3H)。

[0703]A mixture of methyl 3-cyano-benzoate (2g, 12mmol) and hydrazine monohydrate (0.60mL, 12mmol) in ethanol (10mL) was stirred at room temperature overnight. The reaction mixture was concentrated and the resulting residue triturated with diethyl ether to give 3-cyano-benzoyl hydrazine (1.02g, 51%, pink solid).¹HNMR(DMSO)，δ(ppm)：10.31(s，1H)，8.21(m，1H)，8.11(m，1H)，7.99(m，1H)，7.70(m，1H)，4.50(s，1H)。

[0704] Example 109

[0705] 2-chloro-isonicotinyl hydrazide

[0706]HOBt (823mg, 6.09mmol), and EDCI (1.2g, 6.09mmol) were added to a suspension of 2-chloro-isonicotinic acid (800mg, 5.08mmol) in acetonitrile (10.3ml) at room temperature. After 2 hours, a solution of hydrazine monohydrate (0.493ml, 10.2mmol) in acetonitrile (5.0ml) was added dropwise at 0 deg.C. After 30 min, the solvent was removed in a rotary evaporator and the resulting residue was diluted with ethyl acetate, quenched by addition of water, dried over sodium sulfate, filtered and concentrated to give 2-chloro-isoniazid (493mg, 57%, yellow solid). ¹HNMR(DMSO)δ(ppm)：10.21(bs，1H)，8.55(d，1H)，7.82(s，1H)，7.75(d，1H)，4.69(bs，2H)。

[0707] The following compounds were prepared in a similar manner to example 109:

example No. 2	Name (R)
example No. 2	Name (R)	110	2-fluoro-5-methyl-benzoylhydrazines
111	Pyrimidine-4-carboxylic acid hydrazides	110	2-fluoro-5-methyl-benzoylhydrazines

[0708] The following compounds were prepared in a similar manner to example 6:

example No. 2	Name (R)
example No. 2	Name (R)	112	3-fluoro-N-hydroxy-benzamidine
113	N-hydroxy-thiophene-3-carboxamidines	112	3-fluoro-N-hydroxy-benzamidine
113	N-hydroxy-thiophene-3-carboxamidines	114	2-chloro-N-hydroxy-propionamidine
115	3, N-dihydroxy-benzamidines	114	2-chloro-N-hydroxy-propionamidine
115	3, N-dihydroxy-benzamidines	116	N-hydroxy-2-methyl-benzamidine
117	N-hydroxy-2- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthio) -acetamidines	116	N-hydroxy-2-methyl-benzamidine
117		118	3-chloro-N-hydroxy-benzamidine
119	N-hydroxy-2- (4- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthio) -acetamidines	118	3-chloro-N-hydroxy-benzamidine
119		120	2, 5-difluoro-N-hydroxy-benzamidine

[0709] The following compounds were prepared in a similar manner to example 31:

example No. 2	Name (R)
example No. 2	Name (R)	121	4-methyl-5-pyrimidin-3-yl-4H- [1, 2, 4]Triazole-3-thiols
122	4-butyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiols	121	4-methyl-5-pyrimidin-3-yl-4H- [1, 2, 4]Triazole-3-thiols
122	4-butyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiols	123	4 (3-methoxy-propyl) -5-thiophen-2-yl 4H- [1, 2, 4]Triazole-3-thiols
124	4-benzyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiols	123
124	4-benzyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiols	125	4-furan-2-ylmethyl-5-thiophen-2-4H- [1, 2, 4 ]Triazole-3-thiols
126	5-thiophen-2-yl-4-thiophen-2-ylmethyl-4H- [1, 2, 4]Triazole-3-thiols	125
126		127	4-Ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiols
128	4-furan-2-ylmethyl-5-pyridin-4-yl-4H- [1, 2, 4]Triazole-3-thiols	127	4-Ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiols
128		129	4-Ethyl-5-pyridin-4-yl-4H- [1, 2, 4]Triazole-3-thiols
130	4-Ethyl-5-pyridin-3-yl-4H- [1, 2, 4]Triazole-3-thiols	129	4-Ethyl-5-pyridin-4-yl-4H- [1, 2, 4]Triazole-3-thiols
130	4-Ethyl-5-pyridin-3-yl-4H- [1, 2, 4]Triazole-3-thiols	131	4-Ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiols
132	4-furan-2-ylmethyl-5-pyridin-3-yl-4H- [1, 2, 4]Triazole-3-thiols	131	4-Ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiols
132		133	4-Ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazole-3-thiols
134	4-Ethyl-5- (3-fluoro-phenyl) -4H- [1, 2, 4]Triazole-3-thiols	133	4-Ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazole-3-thiols
134		135	4-Ethyl-5- (4-fluoro-phenyl) -4H- [1, 2, 4]Triazole-3-thiols
136	5- (2-fluoro-5-methyl-phenyl) -4-furan-2-ylmethyl-4H- [1, 2, 4]Triazole-3-thiols	135
136		137	4-Ethyl-5- (3-methyl-thiophen-2-yl) -4H- [1, 2, 4]Triazole-3-thiols
138	4-Ethyl-5- (5-methyl-thiophen-2-yl) -4H- [1, 2, 4]Triazole-3-thiols	137
138		139	5- (2-chloro-6-methyl-pyridin-4-yl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols
140	5- (5-bromo-furan-2-yl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols	139
140		141	4-Ethyl-5- (3-methoxy-thiophen-2-yl) -4H- [1, 2, 4 ]Triazole-3-thiols
142	4-Ethyl-5- (tetrahydro-furan-2-yl) -2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones	141
142		143	4-ethyl-5-thio-4, 5-dihydro-1H- [1, 2, 4]Triazole-3-carboxylic acid methyl ester

[0710] The following compounds were prepared in a similar manner to example 36:

example No. 2	Name (R)
example No. 2	Name (R)	144	5- (2-chloro-pyridin-4-yl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols
145	5- (2-chloro-6-methoxy-pyridin-4-yl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols	144
145		146	4-Ethyl-5- (3-methyl-3H-imidazol-4-yl) -4H- [1, 2, 4]Triazole-3-thiols
147	4-propyl-5-pyridin-4-yl-4H- [1, 2, 4]Triazole-3-thiols	146
147	4-propyl-5-pyridin-4-yl-4H- [1, 2, 4]Triazole-3-thiols	148	4-Ethyl-5- (1-methyl-1H-imidazole) -2-yl) -4H- [1, 2, 4]Triazole-3-thiols
149	4-Ethyl-5- (1-methyl-1H-imidazol-4-yl) -4H- [1, 2, 4]Triazole-3-thiols	148
149		150	3- (5-mercapto-4-methyl-4H- [1, 2, 4)]Triazol-3-yl) -benzonitrile
151	5- (3-chloro-phenyl) -4-methyl-4H- [1, 2, 4]Triazole-3-thiols	150
151		152	5- (4-chloro-phenyl) -4-methyl-4H- [1, 2, 4]Triazole-3-thiols
153	5- (2-fluoro-phenyl) -4-methyl-4H- [1, 2, 4]Triazole-3-thiols	152
153		154	55- (3-fluoro-phenyl) -4-methyl-4H- [1, 2, 4]Triazole-3-thiols
155	5- (4-fluoro-phenyl) -4-methyl-4H- [1, 2, 4]Triazole-3-thiols	154
155		156	5-benzo [ b ]]thien-2-yl-4-methyl-4H- [1, 2, 4 ]Triazole-3-thiols
157	5- (3-methoxy-phenyl) -4-methyl-4H- [1, 2, 4]Triazole-3-thiols	156
157		158	5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4]Triazole-3-thiols
159	4-Ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4]Triazole-3-thiols	158
159		160	5- (3, 5-difluoro-phenyl) -4-ethyl 4H- [1, 2, 4]Triazole-3-thiols
161	5- (2, 6-difluoro-phenyl) -4-ethyl 4H- [1, 2, 4]Triazole-3-thiols	160
161		162	5- (4-butoxy-phenyl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols
163	5-benzo [1, 3]]Dioxol-5-yl 4-ethyl-4H- [1, 2, 4]Triazole-3-thiols	162
163		164	4-Ethyl-5-pyrimidin-5-yl 2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones
165	4-Ethyl-5-furan-3-yl-2, 4-dihydro- [1, 2, 4]Triazole-3-thiones	164
165		166	4- (tetrahydrofuran-2-ylmethyl) -5-thiophen-2-yl-2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones
167	5-cyclopentyl-4-ethyl-dihydro- [1, 2, 4]Triazole-3-thiones	166
167	5-cyclopentyl-4-ethyl-dihydro- [1, 2, 4]Triazole-3-thiones	168	4-Ethyl-5- [2- (4-methoxy-phenyl) -ethyl]-2, 4-dihydro- [1, 2, 4]Triazole-3-thiones

[0711] Example 169

[0712]5- (3, 5-dichloro-phenyl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol

[0713] 3, 5-dichloro-benzoic acid (382mg, 2mmol) and triethylamine (606mg, 3mmol) were mixed in THF (6ml) at 10 ℃. Isobutyl chloroformate (300mg, 2.2mmol) was then added dropwise and stirred for 45 minutes. 4-methyl-3-thiosemicarbazide (238.4mg, 2mmol) was added to the reaction mixture. After stirring for 10 minutes at room temperature, the reaction mixture was heated at 70 ℃ overnight. Standard post-processing. This product was purified by column chromatography using 25-30% ethyl acetate in hexane to yield 46.4mg (8.5%) of 5- (3, 5-dichloro-phenyl) -4-ethyl-4H- [1, 2, 4] triazole-3-thiol.

[0714] The following compounds were prepared according to a similar method to example 169:

example No. 2	Name (R)
example No. 2	Name (R)	170	5- (3-methylphenyl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols
171	5- (4-methylphenyl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols	170	5- (3-methylphenyl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols
171	5- (4-methylphenyl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols	172	4-Ethyl-5- (3-nitrophenyl) -4H- [1, 2, 4]Triazole-3-thiols
173	5- (2, 5-difluorophenyl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols	172	4-Ethyl-5- (3-nitrophenyl) -4H- [1, 2, 4]Triazole-3-thiols
173		174	5- (3-chlorophenyl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols
175	5- (4-chlorophenyl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols	174	5- (3-chlorophenyl) -4-ethyl-4H- [1, 2, 4]Triazole-3-thiols

[0715] Example 176

[0716] 4-Ethyl-5-methoxymethyl-2, 4-dihydro- [1, 2, 4] triazole-3-thione

[0717]Step 1: n-ethyl-2- (methoxyacetyl) hydrazine thiocarboxamide: methoxyacetic acid (360mg, 3.99mmol), 4-ethyl 3-thiosemicarbazide (581mg, 4.87mmol), diisopropylcarbodiimide (615mg, 4.87mmol) and hydroxybenzotriazole (69.6mg, 0.51mmol) in dimethylformamideThe amine (10ml) was mixed and stirred under argon at room temperature for 19 hours. The crude product obtained after evaporation drying was used directly in the next step. MS (ESI) M/z 192(M + 1). Step 2: 4-Ethyl-5-methoxymethyl-2, 4-dihydro- [1, 2, 4 [ ]]Triazole-3-thione: N-Ethyl 2- (methoxyacetyl) dithiocar-boxamide (760mg of crude product, 4mmol) and sodium hydrogen carbonate (560mg, 6.6mmol) were suspended in water (15ml) and refluxed for 5 hours. After cooling, filtration was carried out, and the filtrate was acidified with concentrated hydrochloric acid and extracted with ethyl acetate. The crude product was recrystallized from ethyl acetate/hexane after evaporation to dryness. The mother liquor was filtered and recrystallized to jointly yield 325mg (47%) of the title compound. ¹HNMR(CDCl₃)，δ(ppm)：4.47(s，2H)，4.13(q，2H)，3.37(s，3H)，1.38(t，3H)。

[0718] The following compounds were prepared according to a similar procedure to example 176:

example No. 2	Name (R)
example No. 2	Name (R)	177	4-methyl-5-pyridin-4-yl 2, 4-dihydro- [1, 2, 4]Triazole-3-thiones
178	4-allyl-5-furan-2-yl 2, 4-dihydro- [1, 2, 4]Triazole-3-thiones	177
178		179	4-Ethyl-5- (4-methoxy-phenoxymethyl) -2, 4-dihydro- [1, 2, 4]Triazole-3-thiones
180	4-ethyl-5-phenoxymethyl-2, 4-dihydro- [1, 2, 4]Triazole-3-thiones	179
180		181	4-Ethyl-5-hydroxymethyl 2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones
182	4-Ethyl-5- (2-methoxy-ethyl) -2, 4-dihydro- [1, 2, 4]Triazole-3-thiones	181
182		183	4-ethyl-5-methylthiomethyl-2, 4-dihydro- [1, 2, 4]Triazole-3-thiones
184	5-ethoxymethyl-4-ethyl-2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones	183
184		185	5-furan-3-yl-4-methyl-2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones
186	4-methyl-5-pyrimidin-4-yl-2, 4-dihydro- [1, 2, 4]Triazole-3-thiones	185
186		187	4-Ethyl-5-pyridazin-4-yl-2, 4-dihydro- [1, 2, 4]Triazole-3-thiones
188	4-Ethyl-5-pyridin-4-ylmethyl-2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones	187
188		189	4-Ethyl-5 (6-hydroxypyridin-3-yl) -2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones
190	4-Ethyl-5- (4-hydroxy-phenyl) -2, 4-dihydro- [1, 2, 4 ]Triazole-3-thiones	189
190		191	4-Ethyl-5-p-tolyloxymethyl-2, 4-dihydro- [1, 2, 4%]Triazole-3-thiones
192	4-Ethyl-5- (6-methoxy-pyridin-3-yl) -2, 4-dihydro- [1, 2, 4]Triazole-3-thiones	191
192		193	4-Ethyl-5 (2-methoxy-pyridin-4-yl) -2, 4-dihydro- [1, 2, 4]Triazole-3-thiones
194	4-Ethyl-5-pyrimidin-2-yl 2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones	193
194		195	4-Ethyl-5- (5-methoxy-pyrimidin-2-yl) -2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones

[0719] Example 196

[0720] 4-furan-2-ylmethyl-4H- [1, 2, 4] triazole-3-thiol

[0721]A solution of formylhydrazine (439mg, 7.809mmol) in pyridine (20ml) was added to a solution of 2-isothiocyanatomethyl-furan (1g, 7.185mmol) in pyridine (20 ml). The reaction was allowed to proceed overnight at room temperature, and ethanol (20ml) was added directly to the reaction and placed in a water bath at 80 ℃ overnight. The solvent was removed by evaporation and purified by SPE chromatography on silica gel using 500ml 20%, 250ml 25%, 250ml 30%, 250ml 35%, 250ml 40% and 250ml 50% ethyl acetate in hexane to give the title compound (1.09g, 83%).¹HNMR(CD₃OD)，δ(ppm)：14.0(bs，1H)，8.19(s，1H)，7.52(q，1H)，6.52(m，1H)，6.42(m，IH)，4.90(s，2H)。

[0722] The following compounds were prepared in a similar manner to example 196:

example No. 2	Name (R)
example No. 2	Name (R)	197	4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4 ]Triazole-3-thiols
198	4-cyclopropylmethyl-5-pyridin-4-yl-4H- [1, 2, 4]Triazole-3-thiols	197

[0723] Example 199

[0724] 4-cyclopropyl-5-thiophen-2-yl 2, 4-dihydro- [1, 2, 4] triazole-3-thione

[0725]To a slurry of thiophene-2-carbonyl hydrazine (866mg, 6.09mmol) in iPrOH (25ml) was added isothiocyanatocyclopropane (602mg, 6.08 mmol). The mixture was stirred at 70 ℃ for 72 hours and then cooled to room temperature. The white precipitate was filtered off and suspended in MeOH: H₂O (9: 1, 40ml) and containing aq. NaOH (2%, 5 ml). The reaction mixture was stirred at 70 ℃ overnight and cooled to room temperature. The pH was adjusted to about 4 with aq. HCl (1N). The precipitate formed was filtered off, washed with water and dried in vacuo (829mg, 61%).¹HNMR(CD₃OD)，δ(ppm)：7.67(dd，1H)，7.63(dd，1H)，7.17(dd，1H)，3.15(m，1H)，1.14(m，2H)，0.86(m，2H).

[0726] The following compounds were prepared in a similar manner to example 199:

example No. 2	Name (R)
example No. 2	Name (R)	200	5-Furan-2-yl-4- (2-methoxy-ethyl) -2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones
201	4-cyclopropyl-5-furan-2-yl-2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones	200
201		202	(3-Thien-2-yl-5-thio-1, 5-dihydro- [1, 2, 4)]Triazol-4-yl) -acetic acid methyl ester
203	4-Cyclopropylmethyl-5-thiophen-2-yl-2, 4-dihydro- [1, 2, 4-]Triazole-3-thiones	202
203		204	4- (2-methoxy-ethyl) Base) -5-thiophen-2-yl 2, 4-dihydro- [1, 2, 4]Triazole-3-thiones
205	Thien-2-yl-4- (2, 2, 2-trifluoroethyl) -2, 4-dihydro- [1, 2, 4]Triazole-3-thiones	204
205		206	4-cyclopropyl-5-pyrimidin-4-yl 2, 4-dihydro- [1, 2, 4]Triazole-3-thiones
207	4-cyclopropyl-5-pyridin-3-yl 2, 4-dihydro- [1, 2, 4]Triazole-3-thiones	206

[0727] Examples 208

[0728] 4-Ethyl-5-trifluoromethyl-4H- [1, 2, 4] triazole-3-thiol

[0729]To a solution of 4-ethyl-3-thiosemicarbazide (2.38g, 20mmol) and triethylamine (6.06g, 60mmol) in THF (30ml) was added trifluoroacetic anhydride (5.04g, 24 mmol). The reaction mixture was stirred at room temperature for 1 hour and heated to 60 ℃ overnight. Standard work-up, trituration of the product with hexane gave 564g of 4-ethyl-5-trifluoromethyl-4H- [1, 2, 4]Triazole-3-thiol is a light brown solid.¹HNMR(CDCl₃) δ (ppm): 12.64(w, 1H), 4.22(q, 2H) and 1.44(t, 3H).

[0730] Example 209

[0731] 4-Ethyl-3-methanesulfonyl 5-thiophen-2-yl-4H- [1, 2, 4] triazole

[0732]The title CompoundPrepared according to the method described in Akerblom et al J.Med.chem.16, 312 (1973). 4-ethyl-3-methylsulfanyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole (1.14g, 5.06mmol) was dissolved in glacial acetic acid (20ml) and 30% hydrogen peroxide (5ml) was added. After stirring at room temperature for 16 hours, 30% hydrogen peroxide (5ml) was added. The mixture was stirred at room temperature for 3 hours and then heated to 100 ℃ for 2.5 hours. After cooling in an ice/water bath, the reaction was neutralized by addition of sodium hydroxide and extracted twice with dichloromethane. The organic layers were combined, evaporated to dryness and dried in vacuo to give the title compound (0.78g, 60%). ¹HNMR(CDCl₃)，δ(ppm)：7.60(d，1H)，7.56(d，1H)，7.22(m，1H)，4.51(q，2H)，3.58(s，3H)，1.55(t，3H)。

[0733] The following compounds were prepared in a similar manner to example 209:

example No. 2	Name (R)
example No. 2	Name (R)	210	4- (5-methanesulfonyl-4-methyl-4H- [1, 2, 4]]Triazol-3-yl) -pyridines

[0734] Example 211

[0735]4- (2-hydroxy-ethyl) -5-thiophen-2-yl-2, 4-dihydro- [1, 2, 4] triazole-3-thione

[0736](3-Thien-2-yl-5-thio-1, 5-dihydro- [1, 2, 4] was added dropwise to a slurry of LAH (38.1mg, 1.00mmol) in anhydrous THF (8ml)]Triazol-4-yl) -acetic acid (101mg, 0.42mmol) in dry THF (4 ml). The mixture was reacted for 2 hours and then saturated aq₂SO₄(10ml) quench. THF was removed under reduced pressure, the residue was acidified with aq.hcl (3N) and partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (3X 20 mL). The combined organic layers were washed with brine (15ml) and dried (MgSO)₄) The crude product was concentrated under reduced pressure and used in the next step without purification.¹HNMR(DMSO-d6)δ(ppm)：13.94(s，1H)，7.86(d，1H)；7.81(d，1H)，7.24(dd，1H)，5.09(t，1H)，4.16(t，2H)，3.76(app.q，2H)。

[0737] Example 212

[0738]4- (4, 5-dimethyl-4H- [1, 2, 4] triazol-3-yl) -pyridine

[0739]860. mu.l (10mmol) of oxalyl chloride are slowly added to 731mg (10mmol) of N-methylacetamide and 2.33ml (20mmol) of 2, 6-lutidine in 20ml of CH at 0 DEG C₂Cl₂In the solution of (1). After 15 minutes 1.37g (10mmol) of isonicotinyl hydrazide are added in one portion. The resulting mixture was stirred at room temperature for 1 hour and NaHCO was used ₃(saturation) neutralization reaction. Separating the aqueous phases with CH₂Cl₂And (4) extracting. The combined organic phases were dried and concentrated. The residue was dissolved in 20ml of acetic acid and heated to 120 ℃ for 2 hours. After cooling, the solvent was removed. By flash Chromatography (CH)₂Cl₂MeOH 10: 1) gave 765mg (44%) of an ash/white solid.¹HNMR(CDCl₃)，δ(ppm)：2.52(s，3H)3.66(s，3H)7.58(d，2H)8.76(d，2H)。

[0740] Example 213

[0741] Methyl- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -amine

[0742]A mixture of 1000mg (4.35mmol) N-amino N', N "-dimethyl-guanidinium hydroiodide (Henry; Smith; J.Amer.chem.Soc; 73; 1951; 1858) and 774mg (4.35mmol) isonicotinoyl chloride hydrochloride in 3ml pyridine is heated with microwaves at 160 ℃ for 5 minutes. AddingInto K₂CO₃(saturated) and the mixture was taken up in CHCl₃The extraction was carried out 4 times. The organic phase was dried and concentrated. Recrystallization from ethanol, water and EtOAc afforded 216mg (26%) of an off-white solid.¹HNMR(DMSO)δ(ppm)：2.85(d，3H)3.45(s，3H)6.25(d，1H)7.65(m，2H)8.67(m，2H)。

[0743] Example 214

[0744] 3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrimidine

[0745]A solution of 750mg (3.1mmol) (1, 4, 5, 6-tetrahydro-pyrimidin-2-yl) -hydrazinium hydroiodide (ref. Krezel, IZabella; Pharmazie; EN; 49; 1; 1994; 27-31) and 552mg (3.1mmol) isonicotinoyl chloride hydrochloride in 3ml pyridine is heated at 120 ℃ overnight. After cooling the reaction mixture, K is added ₂CO₃(saturated) diluted and extracted with 3X 10ml of chloroform. The combined organic layers were dried and concentrated. By flash Chromatography (CH)₂Cl₂MeOH 10: 1) gave 83mg (18%) of a white solid.¹HNMR(CDCl₃)，δ(ppm)：1.91(m，2H)3.24(m，2H)4.13(m，2H)7.67(m，2H)8.65(m，2H)。

[0746] The following compounds were prepared in the same manner as in example 214:

example No. 2	Name (R)
example No. 2	Name (R)	215	3-furan-2-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4]Triazole [4, 3-a ]]Pyrimidines

[0747] Example 216

[0748] 4-Ethyl-5- (6-methoxy-pyridazin-3-yl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione

[0749]Step 1: 6-chloro-pyridazine-3-carboxylic acid: potassium dichromate (3.3g, 11.2mmol) was added in portions to 3-chloro-6-methyl-pyridazine (1.2g, 9.3mmol) in H₂SO₄(10ml) in solution. The mixture was stirred at above 50 ℃. The reaction was poured onto ice and extracted 3 times with diethyl ether. The combined organic phases were dried and concentrated to give the title compound (840mg, 57%). LC-MS (M + + 1): 159 and 161 (3: 1). Step 2: 6-chloro-pyridazine-3-carboxylic acid methyl ester: a solution of 6-chloro-pyridazine-3-carboxylic acid (700mg, 4.53mmol) in thionyl chloride (15ml) was refluxed for 3 hours. The reaction was cooled to room temperature and evaporated to dryness. To the residue was added a solution of sodium methoxide (244mg, 4.53mmol) in MeOH (20ml), and the resulting solution was stirred further at room temperature. Addition of H ₂O and extracted 3 times with DCM. The combined organic phases were dried and concentrated. Flash chromatography (SiO)₂heptane/EtOAc 1: 1) gave 560mg (72%) of the title compound.¹HNMR(CDCl₃) δ (ppm): 4.09(s, 3H), 7.69(d, 1H), 8.18(d, 1H). LC-MS (M + + 1): 173 and 175 (3: 1). And step 3: 6-methoxy-pyridazine-3-carboxylic acid methyl ester: a solution of methyl 6-chloro-pyridazine-3-carboxylate in NaOMe and MeOH (1M, 10ml) was refluxed. Water was added and the mixture was extracted 3 times with DCM to give organic phase I. The combined organic phases I were dried and concentrated to give the title compound (40mg, 0%). The aqueous phase was acidified with concentrated hydrochloric acid and extracted 3 times with DCM to give organic phase II. The combined organic phases II were dried and concentrated to give 6-methoxypyridazine 3-carboxylic acid (LC-MS (M + + 1): 155) (230mg, 65%). A solution of 6-methoxypyridazine 3-carboxylic acid in thionyl chloride (6ml) was refluxed for 3 hours. The reaction was cooled to room temperature and evaporated to dryness. MeOH (10ml) was added to the residue and the resulting solution was stirred further at room temperature. Adding saturated NaHCO into the mixture₃(aqueous solution) post-useDCM was extracted 3 times. The combined organic phases were dried and concentrated to give the title compound (253mg, 100%). LC-MS (M + + 1): 169. and 4, step 4: 4-Ethyl-5- (6-methoxy-pyridazin-3-yl) -2, 4-dihydro- [1, 2, 4 ]Triazole-3-thione: NaOMe (86mg, 1.6mmol) was added to a solution of methyl 6-methoxy-pyridazine-3-carboxylate (210mg, 1.25mmol) and 4-ethyl-3-thiosemicarbazide (190mg, 1.6mmol) in MeOH (6ml) and the mixture was heated to 70 ℃ for 72 h. The reaction was cooled to ambient temperature and evaporated to dryness. H is to be₂O (10ml) was added to the residue, and the resulting mixture was acidified with concentrated hydrochloric acid and filtered to collect the title compound (35 mg, 12%). LC-MS (M + + 1): 238.

[0750] example 217

[0751] 4-Ethyl-5- (5-methoxypyridin-2-yl) -2, 4-dihydro- [1, 2, 4] triazole-3-thione

[0752]Step 1: 5-methoxy-pyridine-2-carboxylic acid methyl ester: 5-methoxy-2-methyl-pyridine (700mg, 5.69mmol) was dissolved in H₂O (20ml) and heated to 80 ℃. KMnO was added to the solution in portions over 1 hour₄(4g, 25.3 mmol). After stirring at 80 ℃ for 5 hours, the mixture is filtered and the filtrate is taken up in H₂O (60 ℃ C.) washing. The combined aqueous phases were concentrated. DMF (20ml), K₂CO₃(785mg, 5.7mmol) and MeI (540ml, 8.6mmol) were added to the remaining residue and the mixture was heated to 80 ℃. The reaction was cooled to ambient temperature, water was added and the mixture was extracted three times with toluene. The combined organic phases were dried and concentrated. Flash chromatography (SiO) ₂heptane/EtOAc 1: 1) gave 210mg (22%) of the title compound.¹HNMR(CDCl₃) δ (ppm): 3.93(s, 3H)4.00(s, 3H)7.23(m, 1H), 8.13(d, 1H)8.40(d, 1H). Step 2: 4-Ethyl-5- (5-methoxy-pyridin-2-yl) -2, 4-dihydro- [1, 2, 4]Triazole-3-thione: NaOMe (4ml, 4.0mmol, 1M) was added to a solution of methyl 5-methoxy-pyridine-2-carboxylate (200mg, 1.2mmol), 4-ethyl-3-thiosemicarbazide (145mg, 1.2mmol) in MeOH (10ml) and the mixture was heated to 70 ℃. The reaction was cooled to room temperature and evaporated to dryness. H is to be₂O (10ml) was added to the residue, and the resulting mixture was acidified with concentrated hydrochloric acid and collected by filtration to obtain a standardTitle compound 50mg (18%). LC-MS (M + + 1): 237.

[0753] the following compounds were prepared in a similar manner to example 10:

example No. 2	Name (R)
example No. 2	Name (R)	218	5-chloromethyl-3-phenyl- [1, 2, 4]Oxadiazoles as herbicides
219	5-chloromethyl-3- (3-fluoro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	218	5-chloromethyl-3-phenyl- [1, 2, 4]Oxadiazoles as herbicides
219		220	5-chloromethyl-3- (2-fluoro-5-methyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides
221	5-chloromethyl-3-thiophen-2-yl- [1, 2, 4]Oxadiazoles as herbicides	220
221		222	5-chloromethyl radical-3-thiophen-3-yl- [1, 2, 4]Oxadiazoles as herbicides
223	3- (5-chloromethyl- [1, 2, 4)]Oxadiazol-3-yl) -phenols	222
223	3- (5-chloromethyl- [1, 2, 4)]Oxadiazol-3-yl) -phenols	224	5-chloromethyl-3-o-tolyl- [1, 2, 4 ]Oxadiazoles as herbicides
225	5-chloromethyl-3- (3-chloro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	224
225		226	5-chloromethyl-3- (2, 5-difluoro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides

[0754] The following compounds were prepared in a similar manner to example 16:

example No. 2	Name (R)
example No. 2	Name (R)	227	3- (3-chloromethyl [1, 2, 4]]Oxadiazol-5-yl) -benzonitriles
228	2-chloro-4- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -pyridines	227	3- (3-chloromethyl [1, 2, 4]]Oxadiazol-5-yl) -benzonitriles
228		229	3-chloromethyl-5- (2, 5-dimethyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides
230	3-chloromethyl-5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	229
230		231	3-chloromethyl-5- (2, 5-dichloro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides
232	3-chloromethyl-5- (2-fluoro-5-bromo-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	231
232		233	3-chloromethyl-5- (3-methyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides
234	3-chloromethyl-5- (2, 5-difluoro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	233
234		235	3-chloromethyl-5- (3-methylsulfanyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides
236	3-chloromethyl-5- (3-cyclopropyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	235
236		237	3- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -phenyl) -carbamic acid tert-butyl ester
238	1- [3- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -phenyl]-ethanones	237
238		239	5- (5-chloro-2-fluoro-phenyl) -3-chloromethyl- [1, 2, 4]Oxadiazoles as herbicides
240	2- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -4-methyl-phenol	239

[0755] Example 241

[0756] 3-chloromethyl 5- (2-chloro-5-methylphenyl) - [1, 2, 4] oxadiazole

[0757] 2-chloro-5-methyl-benzoic acid (1g, 5.8mmol) was treated with 5ml thionyl chloride under heating reflux for 2 hours. Excess thionyl chloride was removed under reduced pressure. The residue was added to a suspension of 2-chloro-N-hydroxyacetamidine (638mg, 5.8mmol) in dichloromethane (10ml) at room temperature. After stirring for 30 minutes, triethylamine (2.04ml, 14.6mmol) was added and stirring was continued for an additional 1 hour. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated. Flash column chromatography with 10-20% ethyl acetate in hexane afforded 460mg of the acyclic ester intermediate. DMF was added to the intermediate and then heated to 135 ℃ for 4 hours to cyclize to form oxadiazole. After cooling, the mixture was washed with water (3 times) and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Purification on flash column chromatography on silica gel with 5% ethyl acetate in hexane afforded the title compound 160mg (2 steps 12%) as a white solid. m/z244 (GCMS).

[0758] The following compounds were prepared in a similar manner to example 241:

example No. 2	Name (R)
example No. 2	Name (R)	242	3-chloromethyl-5- (2, 5-dichloro-thiophen-3-yl) - [1, 2, 4]Oxadiazoles as herbicides
243	3- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -benzonitriles	242
243		244	3-chloromethyl 5- (3-fluoro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides
245	3-chloromethyl-5- (2-methyl-thiazol-4-yl) - [1, 2, 4]Oxadiazoles as herbicides	244
245		246	3-chloromethyl-5- (4-fluoro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides
247	5- (5-bromo-2-fluoro-phenyl) -3-chloromethyl [1, 2, 4]Oxadiazoles as herbicides	246
247		248	3-methyl 5- (4-methyl-thiophen-2-yl) - [1, 2, 4]Oxadiazoles as herbicides
249	5- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -thiophene-3-carbonitriles	248
249		250	2- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -4-methyl-benzonitrile
251	3- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -5-fluoro-benzonitrile	250
251		252	3- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -4-fluoro-benzonitrile
253	4-chloro-2- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -phenols	252
253		254	3- (1-chloro-ethyl) -5- (3-chloro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides
255	3- (1-chloro-ethyl) -5- (3-fluoro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	254
255		256	3- (1-fluoro-ethyl) -5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides

[0759] Example 257

[0760] [3- (3-chloromethyl- [1, 2, 4] oxadiazol-5-yl) -phenyl ] -methanol

[0761]3-hydroxymethylbenzoic acid (175mg, 1.15mmol), as described in Reed, g.a.; dimmel, d.r.; 2-chloro-N-hydroxy-acetamidine (125mg, 1.15mmol) and HBTU were dissolved in anhydrous DMF (4ml) as described in Malcolm, E.W.J.org.chem.1993, 58(23), 6372-6376. After addition of triethylamine (0.48ml, 3.5mmol) the reaction was stirred at ambient temperature overnight. The crude product is purified in dichloromethane and NaHCO ₃Partitioned between (aqueous solution) and dried (MgSO)₄) The organic phase was removed in vacuo to remove dichloromethane. The resulting DMF solution was heated at 120 ℃ overnight. The reaction mixture was concentrated in vacuo and flash chromatographed using a heptane solution containing 25-50% ethyl acetate to give the title compound (64mg, 25%).¹HNMR(CDCl₃)，δ(ppm)：8.15(s，1H)，8.06(d，1H)，7.62(d，1H)，7.53(t，1H)；4.80(d，2H)，4.66(s，1H)；1.99(br.t，1H)。

[0762] The following compounds were prepared analogously to example 257:

example No. 2	Name (R)
example No. 2	Name (R)	258	3-chloromethyl 5- [1- (toluene-4-sulfonyl) -1H-pyrrol-3-yl]-[1，2，4]Oxadiazoles as herbicides
259	3-chloromethyl-5-furan-3-yl- [1, 2, 4]Oxadiazoles as herbicides	258
259		260	3-chloromethyl-5- (5-chloro-thiophen-2-yl) - [1, 2, 4]Oxadiazoles as herbicides

[0763] Example 261

[0764]1- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -ethanol

[0765]Step 1: 1- {1- [5- (3-chloro-phenyl) - [1, 3, 4]]Oxadiazol-2-yl]-ethoxy } -1H-benzotriazole: reacting 2- (1-chloro-ethyl) -5- (3-chloro-phenyl) - [1, 3, 4%]Oxadiazole (109mg, 0.45mmol), hydroxybenzotriazole (76.4mg, 0.56mmol) and potassium iodide (23.0mg, 0.14mmol) were dissolved in DMF (2.5ml) before potassium carbonate (74.0mg, 0.53mmol) was added. After stirring for 24 hours at ambient temperature under argon, the reaction mixture was diluted with ethyl acetate and washed with 2N ammonium chloride solution. After re-extraction of the aqueous layer with ethyl acetate, the combined organic phases were washed with brine and evaporated to dryness. Column chromatography on 12g silica gel with a solution of heptane/ethyl acetate 4/1 gave the title compound after drying in vacuo (129mg, 84%). ¹HNMR(CDCl₃) δ (ppm): 7.94(d, 1H), 7.82(m, 1H), 7.76(m, 1H), 7.46(m, 1H), 7.39-7.27(m, 4H), 5.98(q, 1H), 2.04(d, 3H). Step 2: 1- [5- (3-chloro-phenyl) - [1, 3, 4]]Oxadiazol-2-yl]-ethanol: 1- {1- [5- (3-chloro-phenyl) - [1, 3, 4]]Oxadiazol-2-yl]-ethoxy } -1H-benzotriazole (58.4mg, 0.17mmol) was dissolved in dry THF (3ml) under argon atmosphere. To this mixture was slowly added a solution of 0.1 mole samarium diiodide in THF (5ml, 0.5mmol) over 20 minutes. After stirring for 80 minutes, a further samarium diiodide solution (4ml, 0.4mmol) was added over 5 minutes. After a further 15 minutes Na was added₂S₂O₃The solution quenched the reaction, diluted with diethyl ether and washed with 1 molar hydrochloric acid solution, dried over sodium sulfate and evaporated to dryness. After drying in vacuo, the title compound was obtained as a crude product (36.0mg, 92%), which was used in the next step without purification.¹HNMR(CDCl₃)，δ(ppm)：7.98-7.75(m，2H)，7.50-7.38(m，2H)，5.25(q，1H)，1.74(d，3H)。

[0766] The following compounds were prepared in a similar manner to example 261:

example No. 2	Name (R)
example No. 2	Name (R)	262	[5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4]Oxadiazol-3-yl]-methanol

[0767] Example 263

[0768]1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethanol

[0769]To a solution of 3.19g (30.6mmol) 2, N-dihydroxy-propionamide in 25ml pyridine at 0 ℃ is added 4.3ml (33.7mmol) 3-chloro-benzoyl chloride. The ice bath was removed and the mixture was stirred at room temperature for 25 minutes and heated at reflux for 25 minutes. After cooling, the mixture was poured into water and charged with CH ₂Cl₂The extraction was performed 2 times. The organic phase was dried and concentrated. From the seventhRecrystallization from alkane/EtOAc provided 4.12g (60%) of a white solid.¹HNMR(CDCl₃)，δ(ppm)：1.68(d，3H)2.67(m，1H)5.09(m，1H)7.46(t，1H)7.56(d，1H)8.01(d，1H)8.13(s，1H)。

[0770] Example 264

[0771] [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -methanol

[0772]Step 1: n- {4- [ (Z) - { [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl]Methylene } (oxy) amino]Phenyl } -N, N-dimethylamine: the title compound is prepared according to the general formula as described in Palazzo et al j.heterocyclic. chem. (1979) 16: 1469. 1- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethyl]Pyridinium chloride (1.81g, 5.87mmol) was dissolved in water (20 ml). To this solution was added a solution of 4-nitroso-N, N-dimethylaniline (0.88g, 5.86mmol) dissolved in ethanol (50ml), followed by slow addition of 1 molar sodium hydroxide solution (5.9ml, 5.9mmol) over 3 minutes. After 1 hour, the precipitate formed was filtered, washed with water and air dried to give the title compound (2.08g, moist) which was used directly in the next step. MS (ESI) M/z 344(M + 1). Step 2: [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-yl]-a glycol: reacting N- (4- [ (Z) - { [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl)]Methylene } (oxy) amino]Phenyl) -N, N-dimethylamine (2.08g moist) was suspended in diethyl ether (30ml) and 1 mol aqueous hydrochloric acid was added. The mixture was stirred vigorously for 20 minutes, transferred to a separatory funnel, and diluted with diethyl ether and 1 molar hydrochloric acid solution. After extraction, the aqueous layer was extracted twice more with diethyl ether. The combined organic layers were dried over magnesium sulfate, then evaporated to dryness, and dried in vacuo to give the title compound as a crude product (0.56g, 42% from 1- [5- (3-chloro-phenyl) - [1, 2, 4] ]Oxadiazol-3-ylmethyl]Pyridinium chloride). MS (ESI) M/z 227(M + 1). And step 3: [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-yl]-methanol: 1- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethyl]-pyridinium chloride (99.3mg, 0.44mmol) was dissolved in methanol (4ml) before addition of sodium borohydride (32mg, 0.84 mmol). After 2 hours more sodium borohydride was added and the reaction was allowed to proceed overnight. With dichloromethane and chlorineThe reaction mixture was diluted with ammonium hydroxide solution and stirred vigorously. The organic layer was washed with brine and evaporated to dryness to give crude product. Purification was performed on flash chromatography with heptane/ethyl acetate to give the title compound (32.0mg, 32%).¹HNMR(CDCl₃) δ (ppm): 8.11(s, 1H), 8.00 (apparent d, 1H), 7.56 (apparent d, 1H), 7.46 (apparent t, 1H), 4.87(d, 2H), 2.91(t, 1H).

[0773] Example 265

[0774] 2-chloromethyl-5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] oxadiazole

[0775]2-fluoro-5-methylbenzoyl hydrazine (320mg, 1.9mmol) and 2-chloro-1, 1, 1-triethoxy-ethane (1.9ml) were heated at 120 ℃ for 30 minutes in a sealed vial. The reaction mixture was placed directly on a flash column (silica gel) and purified with 0-5% ethyl acetate in hexane to give 2-chloromethyl-5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4] ]Oxadiazole (284.5mg, 66%).¹HNMR(CDCl₃)，δ(ppm)：7.89(q，1H)，7.36(m，1H)，7.16(t，1H)，4.81(s，2H)，2.43(s，3H)。

[0776] The following compound was prepared in a similar manner to example 265:

example No. 2	Name (R)
example No. 2	Name (R)	266	2-chloromethyl-5- (3-chloro-phenyl) - [1, 3, 4]Oxadiazoles as herbicides
267	4- (5-chloromethyl- [1, 3, 4)]Oxadiazol-2-yl) -2-methyl-pyridines	266
267		268	2-chloromethyl-5-m-tolyl- [1, 3, 4]Oxadiazoles as herbicides
269	3- (5-chloromethyl- [1, 3, 4)]Oxadiazol-2-yl) -benzonitriles	268
269		270	2-chloro-4- (5-chloromethyl- [1, 3, 4)]Oxadiazol-2-yl) -pyridines
271	2- (5-chloro-2-fluoro-phenyl) -5-chloromethyl- [1, 3, 4]Oxadiazoles as herbicides	270

[0777] Example 272

[0778]2- (1-bromo-ethyl) -5- (3-chloro-phenyl) - [1, 3, 4] oxadiazole

[0779]3-chloro-benzoylhydrazine (170mg, 1mmol) and 2-bromo-1, 1, 1-triethoxypropane (1ml) were heated at 120 ℃ for 10 minutes in a sealed vial. The reaction mixture was placed directly on a flash column (silica gel) and purified with 0-50% dichloromethane in hexane. The product was extracted with ethyl acetate, hexane, dichloromethane (1: 19: 2)0) The mixture is purified again by flash column chromatography to obtain 2- (1-bromo-ethyl) -5- (3-chloro-phenyl) - [1, 3, 4]]Oxadiazole (93mg, 32%, colorless oil).¹HNMR(CDCl₃)，δ(ppm)：8.09(t，1H)，7.99(t，1H)，7.55(m，3H)，5.30(m，1H)，2.21(q，3H)。

[0780] The following compounds were prepared in a similar manner to example 272:

example No. 2	Name (R)
example No. 2	Name (R)	273	2- (1-bromo-ethyl) -5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4]Oxadiazoles as herbicides
274	4- [5- (1-bromo-ethyl) - [1, 3, 4]]Oxadiazol-2-yl]-2-methyl-pyridine	273
274		275	2- (1-bromo-ethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4]Oxadiazoles as herbicides
276	2- (1-bromo-ethyl) -5- (3-chloro-benzeneBase) - [1, 3, 4]Oxadiazoles as herbicides	275

[0781] Example 277

[0782]3- (1-bromo-ethyl) -5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole

[0783]A solution of 583mg (2.22mmol) of triphenylphosphine in 2ml of THF is added dropwise at 0 ℃ to a solution of 396mg (2.22mmol) of N-bromosuccinimide in 2ml of THF. After stirring for 20 min 416mg (1.85mmol) of 1- [5- (3-chloro-phenyl) - [1, 2, 4] are added]Oxadiazol-3-yl]Ethanol in 2ml THF solution. After stirring at room temperature overnight, the solvent was removed under reduced pressure. Flash chromatography (heptane/EtOAc 6: 1) afforded 168mg (32%).¹HNMR(CDCl₃)，δ(ppm)：2.12(d，3H)5.21(q，1H)7.47(t，1H)7.57(m，1H)8.03(d，IH)8.15(s，1H)。

[0784] Example 278

[0785]1- [5- (3-chloro-phenyl) -isoxazol-3-yl ] -ethanol

[0786]Step 1: 4- (3-chloro-phenyl) -2, 4-dioxo-butyric acid ethyl ester: sodium hydride (60% oil dispersed phase, 1.24g, 31.1mmol) was added portionwise to a solution of 3-chloroacetophenone (4.0g, 25.9mmol) and diethyl oxalate (4.54g, 31.1mmol) in DMF (32ml) at 0 ℃. The mixture was stirred at room temperature for 1 hour and heated at 80 ℃ for half an hour. After cooling the mixture was treated with 3N HCl and diluted with ethyl acetate. The organic phase was washed with water (3 ×) and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by flash column chromatography using 0-10% ethyl acetate in hexanes to give 4- (3-chloro-phenyl) -2, 4-dioxo-butyric acid ethyl ester (4.43g, 67%, yellow solid). ¹HNMR(CDCl₃) δ (ppm): 15.12(br s, 1H), 7.98(s, 1H), 7.88(d, 1H), 7.58(d, 1H), 7.47(t, 1H), 7.05(s, 1H), 4.39(m, 2H), 1.41(m, 3H). Step 2: 5- (3-chloro-phenyl) -isoxazole-3-carboxylic acid ethyl ester: 4- (3-chloro-phenyl) -2, 4-dioxo-butyric acid ethyl ester (3.0g,11.8mmol) and hydroxylamine hydrochloride (2.46g, 35.4mmol) in methanol (60ml) were heated at 80 ℃ for 4 hours. After cooling, the mixture was filtered and washed with cold methanol to give ethyl 5- (3-chloro-phenyl) -isoxazole-3-carboxylate (2.0g, 71%, white solid).¹HNMR(CDCl₃) δ (ppm): 7.82(s, 1H), 7.72(m, 1H), 7.47(m, 2H), 4.03(s, 3H). A mixture of methyl and ethyl esters (mostly methyl esters). And step 3: 1- [5- (3-chloro-phenyl) -isoxazol-3-yl ethanone: to a screw-cap vial equipped with a stir bar were added methylmagnesium iodide (3M in diethyl ether) (0.79ml, 2.38mmol), toluene (1ml), tetrahydrofuran (0.39ml, 4.77mmol) and triethylamine (1ml, 7.15 mmol). The solution was cooled to 0 ℃ and a solution of ethyl 5- (3-chloro-phenyl) -isoxazole-3-carboxylate (300mg, 1.19mmol) in toluene (5ml) was added. The resulting mixture was stirred at 0 ℃ for 5 hours. The reaction was quenched with 1N hydrochloric acid (solution, 6.5ml, 6.5mmol), diluted with toluene (35ml) and washed with water (50ml), saturated sodium bicarbonate (solution, 30ml), water (50ml) and brine (30 ml). The organic phase was concentrated in vacuo. The separated residue was dissolved in methanol (8ml) and 20% potassium hydroxide (solution, 1 ml). The mixture was stirred at 45 ℃ for 30 minutes. The mixture was concentrated in vacuo at this time. The separated residue was dissolved in toluene (60ml) and washed with water (50ml), saturated sodium bicarbonate (solution, 50ml), water (50 ml). The organic phase was concentrated in vacuo. The crude residue was purified on silica gel with 2% ethyl acetate in hexane to isolate the desired compound as a white solid (156mg, 60%). ¹HNMR(CDCl₃) δ (ppm): 7.77(m, 1H), 7.66(m, 1H), 7.42(m, 2H), 6.90(s, 1H), 2.69(s, 3H). And 4, step 4: 1- [5- (3-chloro-phenyl) -isoxazol-3-yl]-ethanol: adding 1- [5- (3-chloro-phenyl) -isoxazol-3-yl to a screw-cap vial equipped with a stir bar]-ethanone (100mg, 0.45mmol), sodium borohydride (34mg, 0.90mmol) and methanol (3 ml). The mixture was stirred at room temperature for 3 hours. The reaction was quenched by the addition of water (30ml) and brine (30ml) and extracted with dichloromethane (3X 30 ml). The combined organic phases were dried (sodium sulfate), filtered and concentrated, and separated in vacuo to give 1- [5- (3-chloro-phenyl) -isoxazol-3-yl]Ethanol as a white solid (110 mg).¹HNMR(CDCl₃)，δ(ppm)：7.69(m，1H)，7.59(m，1H)，7.37(m，2H)，6.59(s，1H)，5.07(q，1H)，3.45(bs，1H)，1.58(d，3H)。

[0787] The following compounds were prepared in a similar manner to example 278:

example No. 2	Name (R)
example No. 2	Name (R)	279	1- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl]-ethanol

[0788] The following compound is prepared in analogy to the preparation of ethyl 5- (3-chloro-phenyl) -isoxazole-3-carboxylate (step 2 in example 279):

example No. 2	Name (R)
example No. 2	Name (R)	280	5- (2-fluoro-5-methyl-phenyl) -isoxazole-3-carboxylic acid methyl ester
281	5-Thien-3-yl-isoxazole-3-carboxylic acid methyl ester	280
281	5-Thien-3-yl-isoxazole-3-carboxylic acid methyl ester	282	5-phenyl-isoxazole-3-carboxylic acid methyl ester
283	5- (3-chloro-phenyl) -4-methyl-isoxazole-3-carboxylic acid ethyl ester	282	5-phenyl-isoxazole-3-carboxylic acid methyl ester
283		284	5- (2-chloro-thiophen-3-yl) -isoxazole-3-carboxylic acid methyl ester

[0789] Example 285

[0790] [5- (3-chloro-phenyl) -isoxazol-3-yl ] -methanol

[0791]Lithium aluminium hydride (320mg, 8.4mmol) was slowly added to a solution of ethyl 5- (3-chloro-phenyl) -isoxazole-3-carboxylate (2.0g, 8.4) in THF (100ml) at room temperature. After 1 hour, the reaction was quenched with water and then extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by flash column chromatography using 15-40% ethyl acetate in hexane to give [5- (3-chloro-phenyl) -isoxazol-3-yl]Methanol (1.32g, 75%, yellow solid)。¹HNMR(CDCl₃)，δ(ppm)：7.78(s，1H)，7.68(m，1H)，7.43(m，2H)，6.63(s，1H)，4.84(d，2H)，2.23(t，1H)。

[0792] The following compounds were prepared in a similar manner to example 285:

example No. 2	Name (R)
example No. 2	Name (R)	286	[2- (3-chloro-phenyl) -oxazol-4-yl-methanol
287	[3- (3-chloro-phenyl) -isoxazol-5-yl]-methanol	286	[2- (3-chloro-phenyl) -oxazol-4-yl-methanol
287	[3- (3-chloro-phenyl) -isoxazol-5-yl]-methanol	288	5- (thien-3-yl-isoxazol-3-yl) -methanol
289	[5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl]-methanol	288	5- (thien-3-yl-isoxazol-3-yl) -methanol
289	[5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl]-methanol	290	(5-phenyl-isoxazol-3-yl) -methanol
291	[5- (3-chloro-phenyl) -4-methyl-isoxazol-3-yl]-methanol	290	(5-phenyl-isoxazol-3-yl) -methanol
291	[5- (3-chloro-phenyl) -4-methyl-isoxazol-3-yl]-methanol	292	[5- (5-chloro-thiophen-3-yl) -isoxazol-3-yl]-methanol

[0793] Example 293

[0794] Methanesulfonic acid 1- [5- (3-chloro-phenyl) -isoxazol-3-yl ] -ethyl ester

[0795] 1- [5- (3-chloro-phenyl) -isoxazol-3-yl ] -ethanol (110mg, 0.49mmol), dichloromethane (3ml) and triethylamine (0.34ml, 2.46mmol) were added to a screw-cap vial equipped with a stir bar. The mixture was cooled to 0 ℃ and methanesulfonyl chloride (0.08ml, 0.98mmol) was added. The reaction was allowed to stir at room temperature for 30 minutes. The reaction was quenched by the addition of saturated sodium bicarbonate (solution, 40ml) and extracted with dichloromethane (3X 30 ml). The combined organic phases were washed with brine (40ml), dried (sodium sulfate), filtered and concentrated to give the desired compound as a brown oil which was isolated in vacuo.

[0796] The following compounds were prepared in a similar manner to example 293:

example No. 2	Name (R)
example No. 2	Name (R)	294	Methanesulfonic acid 2- (3-chloro-phenyl) -oxazol-4-ylmethyl ester
295	Methanesulfonic acid 3- (3-chloro-phenyl) -isoxazol-5-ylmethyl ester	294
295		296	Methanesulfonic acid 5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-ylmethyl ester
297	Methanesulfonic acid-phenyl-isoxazol-5-yl-ethyl ester	296
297	Methanesulfonic acid-phenyl-isoxazol-5-yl-ethyl ester	298	Methanesulfonic acid 5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-ylmethyl ester
299	Methanesulfonic acid 5- (3-chloro-phenyl) -isoxazol-3-ylmethyl ester	298
299		300	Methanesulfonic acid 5-thiophen-3-yl-isoxazol-3-ylmethyl ester
301	Methanesulfonic acid 5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-ylmethyl ester	300
301		302	Methanesulfonic acid 5-phenyl-isoxazol-3-ylmethyl ester
303	Methanesulfonic acid 5- (3-chloro-phenyl) -4-methyl-isoxazol-3-ylmethyl ester	302	Methanesulfonic acid 5-phenyl-isoxazol-3-ylmethyl ester
303		304	Methanesulfonic acid 5- (5-chloro-thiophen-3-yl) -isoxazol-3-ylmethyl ester
305	Methanesulfonic acid 1- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl]-Ethyl ester	304
305		306	Methanesulfonic acid 1- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl]-Ethyl ester

[0797] Example 307

[0798] Methanesulfonic acid 4-chloro-5- (3-chloro-phenyl) -isoxazol-3-ylmethyl ester

[0799]Sulfonyl chloride (1ml) was added to methanesulfonic acid 5- (3-chloro-phenyl) -isoxazol-3-ylmethyl ester (200mg, 0.70mmol), which was then stirred at 60 ℃ overnight. The reaction mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and concentrated to give 4-chloro-5- (3-chloro-phenyl) -isoxazol-3-ylmethyl methanesulfonate (219mg, 97%, light brown solid).¹HNMR(CDCl₃)，δ(ppm)：8.07(m，1H)，7.92(m，1H)，7.50(m，2H)，5.38(s，2H)，3.16(s，3H)。

[0800] Example 308

[0801]3- (3-chloro-phenyl) -isoxazole-5-carboxylic acid methyl ester

[0802]Step 1: 3-chloro-N-hydroxy-benzamidine: a solution of 3-chlorobenzaldehyde (3.35ml, 0.030mmol) in ethanol (40ml) was added to a solution of hydroxylamine hydrochloride (2.47g, 0.036mmol) and sodium hydroxide (1.42g, 0.036) in water (20ml) at room temperature, followed by heating at 90 ℃ for 24 hours. After cooling, the reaction mixture was concentrated, the residue diluted with water, the precipitate filtered off and dried to give 3-chloro-N-hydroxy-benzamidine (1.13g, 93%). ¹HNMR(CDCl₃) δ (ppm): 8.11(s, 1H), 7.72(s, 1H), 7.61(m, 1H), 7.46(m, 1H), 7.36(m, 1H). Step 2: 3-chloro-N-hydroxybenzylidene chloride: n-chlorosuccinimide (858mg, 6.4mmol) was added to a solution of 3-chloro-N-hydroxy-benzamidine (1g, 6.4mmol) at room temperature and stirred for 1 hour. The reaction mixture was diluted with diethyl ether and washed with water (3 ×), dried over anhydrous magnesium sulfate, filtered, and concentrated to give the title compound (1.13g, 93%).¹HNMR(CDCl₃) δ (ppm): 8.03(s, 1H), 7.87(m, 1H), 7.76(m, 1H), 7.43(m, 1H). And step 3: 3- (3-chloro-phenyl) -isoxazole-5-carboxylic acid methyl ester: triethylamine (0.73ml, 5.3mmol) was added dropwise to a solution of 3-chloro-N-hydroxy-aminobenzylidenechloride (1.0g, 5.3mmol) and methyl propiolate (2.2ml, 25.3mmol) in an ice bath. The reaction mixture was warmed to room temperature and stirred overnight. After the reaction was diluted with dichloromethane, the organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. Flash column chromatography with 50% hexane in ethyl acetateThe solution was purified by elution and recrystallized from methanol to give methyl 3- (3-chloro-phenyl) -isoxazole-5-carboxylate (635mg, 51%, white solid). ¹HNMR(CDCl₃)，δ(ppm)：7.86(m，1H)，7.74(m，1H)，7.46(2H)，7.2(s，1H)，4.05(s，3H)。

[0803] Example 309

[0804] 2-bromomethyl-5- (3-chloro-phenyl) -oxazole

[0805]Step 1: 5- (3-chloro-phenyl) -2-methyl-oxazole: at room temperature to Tl (O Ac)₃(4.2g, 11.1mmol) in acetonitrile (80ml), trifluoromethanesulfonic acid (5g, 33.3mmol) was added dropwise and stirred for 15 min. The reaction mixture was heated to 80 ℃ and a solution of 1- (3-chloro-phenyl) -ethanone (1.14g, 7.4 mmol) in acetonitrile (40ml) was added. After one hour, the reaction was quenched with dichloromethane and saturated sodium bicarbonate. The organic layer was dried and purified by column chromatography using 5-19% ethyl acetate in hexane to give 1.2g (83.9%) 5- (3-chloro-phenyl) -2-methyloxazole as a yellow oil.₁HNMR(CDCl₃) δ (ppm): 7.60(s, 1H), 7.48(d, 1H), 7.29(m, 2H), 7.23(s, 1H) and 2.34(s, 3H). Step 2: 2-bromomethyl-5- (3-chloro-phenyl) -oxazole: 5- (-chloro-phenyl) -2-methyl-oxazole (580mg, 3mmol) was mixed with NBS (531mg, 3mmol) and BPOA (36.3mg, 0.15mmol) in CCl at room temperature₄Mixing the above materials. The reaction mixture was heated at 75 ℃ for 2 hours and quenched with water and dichloromethane. The organic layer was dried, concentrated and purified by column chromatography using 2-5% ethyl acetate in hexane to give 562mg (68.3%) of 2-bromomethyl-5- (3-chloro-phenyl) -oxazole as a yellow oil. ¹HNMR(CDCl₃) δ (ppm): 7.67(s, 1H), 7.54(d, 1H), 7.35(m, 3H) and 4.56(s, 2H).

[0806] Example 310

[0807]2- (3-chloro-phenyl) -oxazole-4-carboxylic acid methyl ester

[0808]To a mixture of 3-chlorobenzoic acid (5.0g, 31.9mmol), serine methyl ester hydrochloride (6.1g, 31.9mmol) and HOBt (4.31g, 31.9mmol) in DMF (100ml) at 0 deg.C was added N-methylmorpholine (NMM) (7)0ml, 63.8mmol) and EDCI (4.97 g. 31.9 mmol). The mixture was warmed to room temperature and stirred for 18 hours. The mixture was diluted with ethyl acetate (300ml) and washed with water and then brine. Organic extract Na₂SO₄Dried (anhydrous) and concentrated in vacuo to give 2- (3-chloro-benzoylamino) -3-hydroxy-propionic acid methyl ester (7.2g, 93%) as a pale yellow solid.¹HNMR(CDCl₃)，δ(ppm)：7.78(s，1H)，7.66(d，1H)，7.45，(dd，1H)，7.34(t，1H)，7.25(br，d，1H)，4.82(m，1H)，4.08(m，2H)，3.79(s，3H)，3.19(br t，IH)。

[0809]To methyl 2- (3-chloro-benzoylamino) -3-hydroxy-propionate (7.2g, 29.6mmol) in CH at-20 deg.C₂Cl₂The solution in (1) was added dropwise to De-oxofluor (7.2g, 32.6 mmol). After stirring for 30 minutes at this temperature, BrCCl was added dropwise₃(3.6g, 18.1mmol) followed by DBU (2.79g, 18.1mmol) was added. The mixture was then stirred at 2-3 ℃ for 8 hours and saturated NaHCO was used₃Quenched and extracted with ethyl acetate. The organic extracts were washed with brine and Na₂SO₄(anhydrous) drying. Purification was performed on flash column chromatography silica gel with ethyl acetate in hexane as eluent to give methyl 2- (3-chloro-phenyl) -oxazole-4-carboxylate (4.1g, 59%) as a yellow solid. ¹HNMR(CDCl₃)，δ(ppm)：8.30(s，1H)，8.12(d，1H)，7.98(dd，1H)，7.45(m，2H)，3.96(s，3H)。

[0810] Example 311

[0811]2- (3-chloro-phenyl) -oxazole-4-carboxylic acid methyl ester

[0812]To a mixture of 3-chlorobenzoic acid (5.0g, 31.9mmol), serine methyl ester hydrochloride (6.1g, 31.9mmol) and HOBt (4.31g, 31.9mmol) in DMF (100ml) was added N-methylmorpholine (NMM) (7.0ml, 63.8mmol) and EDCI (4.97g, 31.9mmol) at 0 ℃. The mixture was warmed to room temperature and stirred for 18 hours. The mixture was diluted with ethyl acetate (300ml) and washed with water (3X 250ml) followed by brine. Organic extract Na₂SO₄(Anhydrous) drying and concentration in vacuo to give 2- (3-chloro-benzoylamino) -3-hydroxy-propionic acid methyl ester (b-chloro-benzoylamino) -27.2g, 93%) as a pale yellow solid.¹HNMR(CDCl₃)，δ(ppm)：7.78(s，1H)，7.66(d，1H)，7.45，(dd，1H)，7.34(t，1H)，7.25(br，d，1H)，4.82(m，1H)，4.08(m，2H)，3.79(s，3H)，3.19(br，d，1H)。

[0813]To methyl 2- (3-chloro-benzoylamino) -3-hydroxy-propionate (7.2g, 29.6mmol) in CH at-20 deg.C₂Cl₂The solution in (1) was added dropwise to De-oxofluor (7.2g, 32.6 mmol). After stirring for 30 minutes at this temperature, BrCCl was added dropwise₃(3.6g, 18.1mmol) followed by DBU (2.79g, 18.1mmol) was added. The mixture was then stirred briefly for 8 hours at 2-3 ℃ and saturated NaHCO was used₃Quenched and extracted with ethyl acetate. The organic extracts were washed with brine and Na₂SO₄(anhydrous) drying. Purification was performed on flash column chromatography silica gel with ethyl acetate in hexane as eluent to give methyl 2- (3-chloro-phenyl) -oxazole 4-carboxylate (4.1g, 59%) as a yellow solid. ¹HNMR(CDCl₃)，δ(ppm)：8.30(s，1H)，8.12(d，1H)，7.98(dd，1H)，7.45(m，2H)，3.96(s，3H)。

[0814] Example 312

[0815]1- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl ] -ethanol

[0816]Step 1: 5- (5-chloro-2-fluoro-phenyl) -isoxazole-3-carbaldehyde: in a 50ml round bottom flask equipped with a stir bar and a dry tube were added 5- (5-chloro-2-fluoro-phenyl) -isoxazole-3-carboxylic acid ethyl ester (0.78g, 2.89mmol) and dichloromethane (10 ml). The solution was cooled to-78 ℃ and diisobutylaluminum hydride (1M hexane, 5.3ml, 5.3mmol) was added to the stirred solution. The resulting mixture was stirred at-78 ℃ for 3 hours. The reaction was quenched with sodium sulfate decahydrate. The resulting mixture was stirred at 63 ℃ for 15 minutes, after which it was filtered through a layer of celite. The filtrate was concentrated in vacuo to isolate an off-white solid which was triturated with hexane to isolate the title compound as a white solid (0.55g, 84%).¹HNMR(CDCl₃) δ (ppm): 10.2(s, 1H), 7.99(m, 1H), 7.44(m, 1H), 7.20(m, 1H), 7.10(d, 1H). Step 2: 1- [5- (5-Chloro-2-fluoro-phenyl) -isoxazol-3-yl]-ethanol: a50 ml round bottom flask equipped with a stir bar was charged with 5- (5-chloro-2-fluoro-phenyl) -isoxazole-3-carbaldehyde (0.55g, 2.42mmol) and tetrahydrofuran (6 ml). The mixture was cooled to 0 ℃ and methylmagnesium iodide (3M in diethyl ether, 3.23ml, 9.67mmol) was added. The resulting mixture was stirred at 0 ℃ for 3 hours. The reaction was quenched with hydrochloric acid (1N, aqueous, 10ml) and extracted with diethyl ether (3X 50 ml). The combined organic phases were washed with water (50ml), brine (50ml), dried (sodium sulphate), filtered and concentrated in vacuo. The crude residue was purified on silica gel with 10% ethyl acetate in hexane to isolate the desired compound as a clear oil (179mg, 31%).

[0817] Example 313

[0818]1- [3- (3-chloro-phenyl) -isoxazol-5-yl ] -ethanol

[0819]3-chloro-benzohydroxamic acid chloride (e.g., Kim, Jae Nyoung; Ryu, Eung K; J. org. chem. (1992), 57(24), 6649-50) (2.84g, 14.8mmol) is suspended in benzene (50ml) and cooled to 0 ℃. 3-butyn-2-ol (2.10g, 29.9mmol) and triethylamine (1.89ml, 26.7mmol) were added. The mixture was heated at 60 ℃ for 1.5 h, cooled and diluted with benzene and 1N hydrochloric acid solution. After stirring, the benzene layer was separated and evaporated to dryness and the crude product was purified by flash chromatography on silica with a solution of heptane/ethyl acetate 5/1 to yield the title compound (0.49g, 15%) after drying in vacuo.¹HNMR(CDCl₃)，δ(ppm)：1.64(d，3H)，5.07(dq，1H)，6.50(s，1H)，7.40(m，2H)，7.68(m，1H)，7.79(m，1H)

[0820] Example 314

[0821] [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl ] -methanol

[0822]Step 1: (5-chloro-2-fluoro-phenylacetylene) -trimethyl-silane: into a 250ml round bottom flask equipped with a stir bar and reflux condenser were added 4-chloro-2-bromo-1-fluoro-benzene (5g, 23.9mmol), triphenylphosphine (250mg, 0.10mmol), (trimethylsilyl) acetylene (5.2ml, 36.5mmol) and triethylamine (60 ml). The reaction mixture was purged with argonWash, add palladium (II) acetate (108mg, 0.05 mmol). The resulting mixture was stirred at reflux under argon overnight. The reaction mixture was filtered through a small piece of celite with ethyl acetate and the filtrate was concentrated in vacuo. The residue separated is taken up on silica gel and filtered through hexane. The filtrate was concentrated in vacuo to isolate the title compound as a brown oil (5.42 g). Step 2: 4-chloro-2-ethynyl 1-fluoro-benzene: to a 250ml round bottom flask equipped with a stir bar were added (5-chloro-2-fluoro-phenylacetylene) -trimethyl-silane (5.42g, 23.9mmol), potassium carbonate (16.5g, 120mmol) and methanol (60 ml). The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with hexane (200ml) and washed with water (250 ml). The aqueous phase was extracted with hexane (2X 100 ml). The combined organic phases were washed with brine (200ml), dried (sodium sulfate), filtered and concentrated in vacuo to isolate the desired compound as a brown oil (3.56 g). ¹HNMR(CDCl₃) δ (ppm): 7.47(dd, 1H), 7.30(m, 1H), 7.05(t, 1H), 3.36(s, 1H). And step 3: chloro-hydroxyimino-acetic acid ethyl ester: to a 1L round bottom flask equipped with a stir bar was added glycine ethyl ester hydrochloride (20g, 143mmol) and water (30 ml). After cooling the solution to 0 ℃ concentrated hydrochloric acid (11.8ml, 143mmol) was added in order and a solution of sodium nitrite (9.89g, 143mmol) in water (15ml) was added dropwise. After 10 minutes the same equivalent of an aqueous solution of concentrated hydrochloric acid and nitrous acid was added. The reaction mixture was stirred at 0 ℃ for 1 hour. The reaction mixture was extracted with diethyl ether (4X 100 ml). The combined organic phases were dried (sodium sulfate), filtered and concentrated in vacuo to isolate a solid of lemon yellow. The solid was isolated by recrystallization from hexane as a white solid (11g, 51%).¹HNMR(CDCl₃) δ (ppm): 9.98(bs, 1H), 4.40(q, 2H), 1.38(t, 3H). And 4, step 4: 5- (5-chloro-2-fluoro-phenyl) -isoxazole-3-carboxylic acid ethyl ester: into a 250ml round bottom flask equipped with a stir bar were added 4-chloro-2-ethynyl-1-fluoro-benzene (2g, 12.9mmol), chloro-hydroxyimino-ethyl acetate (3.92g, 25.9mmol), sodium bicarbonate (7.07g, 84.1mmol) and toluene (50 ml). The reaction mixture was stirred at room temperature for 48 hours. Followed by concentration in vacuo. The residue was dissolved in ethyl acetate (200ml) and washed with water (150ml), brine (150ml), dried (sodium sulphate), filtered and concentrated in vacuo. Crude residue Purification on silica gel with 3% acetone in hexane afforded the title compound as a grey solid (1.56 g).¹HNMR(CDCl₃) δ (ppm): 8.00(dd, 1H), 7.43(m, 1H), 7.18(m, 2H), 4.51(q, 2H), 1.47(t, 3H). And 5: [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl]-methanol: to a 50ml round bottom flask equipped with a stir bar and drying tube was added 5- (5-chloro-2-fluoro-phenyl) -isoxazole-3-carboxylic acid ethyl ester (0.78g, 2.89mmol) and tetrahydrofuran (10 ml). To the stirred solution was added a solution of lithium aluminium hydride (0.12g, 2.89mmol) in tetrahydrofuran (2 ml). The resulting mixture was stirred at room temperature for 1 hour. The reaction was quenched with sodium sulfate decahydrate. The resulting mixture was stirred at 63 ℃ for 15 minutes, after which it was filtered through a pad of celite. The filtrate was concentrated in vacuo to isolate the title compound as a yellow solid (0.65g, 99%).¹HNMR(CDCl₃)，δ(ppm)：7.73(dd，1H)，7.27(m，1H)，7.24(t，1H)，6.73(d，1H)，4.77(s，2H)，4.45(bs，1H)。

[0823] Example 315

[0824]3- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -propionylhydrazine

[0825]Step 1: 3- [5- (3-chloro-phenyl) - [1, 3, 4]]Oxadiazol-2-yl]-propionic acid: 3-chloro-benzoylhydrazine (3.4g, 20mmol) and succinic anhydride (2.g, 20mmol) were mixed in ethyl acetate (50ml) at room temperature for 15 min. The reaction mixture is diluted with diethyl ether and the precipitate is filtered off to give 5.1g of 4- [ N' - (3-chloro-benzoyl) -hydrazino ]-4-oxo-butyric acid.¹HNMR(CDCl₃+ DMSO-d6), δ (ppm): 10.01(s, 1H), 9.53(s, 1H), 7.68(s, 1H), 7.55(d, 1H), 7.21(d, 1H), 7.12(t, 1H) and 2.35(m, 4H). The solid is mixed with concentrated H₂SO₄Mix and stir at room temperature for 45 minutes, then carefully add the reaction mixture to crushed ice (400 g). The precipitate was filtered off to give 4.07g (80.6%) of 3- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]Propionic acid is a white solid.¹HNMR (DMSO-d6) delta (ppm): 12.4(w, 1H), 7.96(s, 1H), 7.91(d, 1H), 7.71(d, 1H), 7.63(t, 1H), 3.15(t, 2H) and 2.82(t, 2H). Step 2: 3- [5- (3-chloro-phenyl))-[1，3，4]Oxadiazol-2-yl]Propionyl hydrazine: reacting 3- [5- (3-chloro-phenyl) - [1, 3, 4 ] at room temperature]Oxadiazol-2-yl]Propionic acid (2.52g, 10mmol) with methyl iodide (5.68g, 40mmol) and K₂CO₃(5.52g, 40mmol) was mixed in DMF (25ml) overnight. The reaction mixture was diluted with ethyl acetate and washed 3 times with water, MgSO₄Dried and concentrated to give 2.57g of 3- [5- (3-chloro-benzene) - [1, 3, 4 ]]Oxadiazol-2-yl]-methyl propionate. The methyl ester (2.54g, 9.52mmol) was mixed with 98% hydrazine hydrate (4.76g, 95.2mmol) in methanol (10ml) for 1 hour. The reaction mixture was concentrated, diluted with water and filtered to give 2.17g (81.4%) of 3- [5- (3-chloro-phenyl) - [1, 3, 4 ] ]Oxadiazol-2-yl]Propionohydrazide is a white solid.¹HNMR(CDCl₃+ DMSO-d6) δ (ppm): 8.75(w, 1H), 7.91(s, 1H), 7.82(d, 1H), 7.42(m, 2H), 3.45(w, 2H), 3.19(t, 2H) and 2.68(t, 2H).

[0826] Example 316

[0827]3- [5- (3-chloro-phenyl) - [1, 3, 4] oxadiazol-2-yl ] -butyryl hydrazine

[0828]Step 1: 2- {1- [5- (3-chloro-phenyl) - [1, 3, 4]]Oxadiazol-2-yl]-ethyl } -malonic acid dimethyl ester: reacting 2- (1-chloro-ethyl) -5- (3-chloro-phenyl) - [1, 3, 4] at 70 deg.C]Oxadiazole (331mg, 1.36mmol) was mixed with dimethyl propionate (360mg, 2/76mmol) and DBU (207mg, 1.36mmol) in acetonitrile 3ml) overnight. The reaction mixture was diluted with dichloromethane and washed with water. The organic layer was dried and concentrated. The residue was purified with 5-20% ethyl acetate in hexane to give 357mg (74.3%) of 2- {1- [5- (3-chloro-phenyl) - [1, 3, 4]]Oxadiazol-2-yl]-ethyl } -malonic acid dimethyl ester is a white solid.¹HNMR(CDCl₃) δ (ppm): 8.03(s, 1H), 7.95(d, 1H), 7.53(d, 1H), 7.47(t, 1H), 4.06(d, 1H), 3.95(m, 1H), 3.84(s, 3H), 3.74(s, 3H) and 1.51(d, 3H). Step 2: 3- [5- (3-chloro-phenyl) - [1, 3, 4]]Oxadiazol-2-yl]-methyl butyrate: 2- {1- [5- (3-chloro-phenyl) - [1, 3, 4] ]Oxadiazol-2-yl]-Ethyl } -malonic acid dimethyl ester (352.8mg, 1.0mmol) was mixed with sodium chloride (76.3mg, 1.3mmol) and a drop of water in DMSO (1.5ml) at 175 ℃ for 1 hour. The reaction mixture was diluted with water and diluted with diAnd (4) extracting methyl chloride. The organic layer was washed with water and concentrated. The residue was purified by column chromatography using 10-20% ethyl acetate in hexane to give 215mg (76.8%) of 3- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]Methyl-butyrate is a clear oil.¹HNMR(CDCl₃) δ (ppm): 8.03(s, 1H), 7.94(d, 1H), 7.53(d, 1H), 7.45(t, 1H), 3.73(s, 3H), 3.67(m, 1H), 3.05(dd, 1H), 2.73(dd, 1H) and 1.50(d, 3H). And step 3: 3- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-butyryl hydrazine: 3- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-Butyrhydrazide (146mg,%) by reacting 3- [5- (3-chloro-phenyl) - [1, 3, 4 ] at room temperature]Oxadiazol-2-yl]Methyl butyrate (215mg, 0.766mmol) was reacted with hydrazine hydrate (0.74ml) in methanol (3ml) for 2.5 hours.¹HNMR(CDCl₃) δ (ppm): 8.03(s, 1H), 7.94(d, 1H), 7.53(d, 1H), 7.46(t, 1H), 7.23(w, 1H), 3.93(w, 2H), 3.71(m, 1H), 2.90(dd, 1H), 2.57(dd, 1H) and 1.50(d, 3H).

[0829] Example 317

[0830]3- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol 5-yl ] -alanine ethyl ester hydrochloride

[0831]Step 1: 3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-propionamide: reacting 3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]Propionic acid (1.6g, 6.33mmol) with SOCl₂(10ml) was reacted at room temperature overnight. The reaction mixture was concentrated in vacuo. The residue was mixed with THF (20ml) and washed with 28% NH₃-H₂O (5ml) the reaction was quenched at 0 ℃. After stirring for 2 hours, the reaction mixture was diluted with dichloromethane and washed with water and brine. The organic layer was dried, concentrated and triturated with hexane to give 1.21g (76%) of 3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-propionamide.¹HNMR(CDCl₃) δ (ppm): 8.07(s, 1H), 7.96(d, 1H), 7.45(m, 2H), 5.60(dw, 2H), 3.32(t, 2H) and 2.87(t, 2H). Step 2: 3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-propionitrile: 3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]Propionamide (1.2g, 4.77mmol) with pyridine (0.829g, 10.5mmol) and trifluoroacetic anhydride (1.2g, 5).72mml) was mixed in dichloromethane (25ml) at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane and washed with water and brine. The organic layer was dried to give 1.1g (98%) of 3- [3- (-chloro-phenyl) - [1, 2, 4] ]Oxadiazol-5-yl]-propionitrile as a light brown oil.¹HNMR(CDCl₃) δ (ppm): 8.09(s, 1H), 7.98(d, 1H), 7.45(m, H), 5.60(dw, 2H), 3.35(t, 2H) and 3.01(t, 2H). And step 3: 3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-alanine ethyl ester hydrochloride: 3- [3- (3-chlorophenyl- [1, 2, 4]]Oxadiazol-5-yl]Properlotin (1.1g, 4.71mmol) was mixed with 24% HCl in ethanol (8ml) overnight. The precipitate was filtered off and washed with diethyl ether to give 0.99g (66%) of 3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-alanine ethyl ester hydrochloride as white solid.¹H-NMR (DMSO-d6) delta (ppm): 11.70(w, 2H), 7.78(m, 2H), 7.64(m, 2H), 4.41(q, 2H), 3.45(t, 2H), 3.22(t, 2H) and 1.28(t, 3H).

[0832] Example 318

[0833]3- [3- (3-chloro-phenyl- [1, 2, 4] oxadiazol-5-yl ] -propionylhydrazine

[0834]Step 1: 3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-propionic acid: 3-chloro-N-hydroxy-benzamidine (4.52g, 26.5mmol) was heated with succinic anhydride (2.65mg, 26.5mmol) in DMF (5ml) at 150 ℃ for one hour. The reaction mixture was cooled and diluted with ethyl acetate. The organic solution was washed with water and brine and concentrated in vacuo. The residue was triturated with 20% ethyl acetate in hexane to give 4.0g (60%) of 3- [3- (3-chloro-phenyl) - [1, 2, 4] ]Oxadiazol-5-yl]Propionic acid is a white solid.¹HNMR(CDCl₃) δ (ppm): 8.08(s, 1H), 7.96(d, 1H), 7.49(d, 1H), 7.42(t, 1H), 3.28(t, 2H) and 3.04(t, 2H). Step 2: 3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]Propionyl hydrazine: the acid was mixed with iodoethane (1.6g, 10.5mmol) and K₂CO₃(1.46, 10.5mmol) in DMF (5ml) for 5 min to form 3- [3- (3-chloro-phenyl) - [1, 2, 4%]Oxadiazol-5-yl]-ethyl propionate. The ethyl ester was treated with a solution of 37% hydrazine (2ml) in ethanol (5ml) at 80 ℃ for 2 hours to give 595mg (65% in 3 steps) 3- [3- (3-chloro-phenyl) - [1, 2, 4]Oxadiazol-5-yl]Propionohydrazide is an off-white solid.¹HNMR(CDCl₃) δ (ppm): 8.07(s, 1H), 7.96(d, 1H), 7.49(d, 1H), 7.43(t, 1H), 7.00(w, 1H), 3.95(w, 2H), 3.34(t, 2H) and 2.79(t, 2H).

[0835] Example 319

[0836] [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl-acethydrazide

[0837]Step 1: (N-hydroxycarbamimidoyl) -acetic acid ethyl ester: to an ethanol solution (40ml) of ethyl cyanoacetate (9.9g, 0.1mol), a mixed solution of a solution of sodium hydroxide (4g, 0.1mol) in water (40ml) and 5M hydroxylamine hydrochloride (20ml) was added, and the reaction mixture was stirred at 50 ℃ overnight. After concentration, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried and concentrated again. The residue was purified by column chromatography using 30-70% ethyl acetate in hexane to give 3.32g (22.7%) (N-hydroxycarbamimidoyl) -ethyl acetate as a white solid. ¹HNMR(CDCl₃) δ (ppm): 5.04(ws 2H), 4.20(q, 2H), 3.19(s, 2H) and 1.30(t, 3H). Step 2: [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethyl acetate: to a solution of (N-hydroxycarbamimidoyl) -acetic acid ethyl ester (1.46g, 10mmol) and triethylamine in dichloromethane (10ml) was slowly added 3-chlorobenzoyl chloride (1.75g, 10mmol) at 5 ℃ and the reaction mixture was stirred for 10 min. DMF (8ml) was added to the reaction mixture and heated at 135 ℃ for 2 h. Standard work-up, the product is eluted with dichloromethane on a column to give 1.2g (45%) [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]Ethyl acetate is a pale yellow oil.¹HNMR(CDCl₃) δ (ppm): 8.168(s, 1H), 8.04(d, 1H), 7.59(d, 1H), 7.49(t, 1H), 4.26(q, 2H), 3.91(s, 2H) and 1.31(t, 3H). And step 3: [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-acetyl hydrazine: 5- (3-chlorophenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]Ethyl acetate (0.64g, 2.4mmol) was mixed with 37% hydrazine (1.6ml) in ethanol (ethabol) (10ml) at 80 ℃ for 4 h. The reaction mixture was concentrated and diluted with water. The precipitate was filtered off and washed with water to give 0.51g (83.3%) [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-acetyl hydrazine.

[0838] Example 320

[0839] (R) -3- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol 5-yl ] -butyryl hydrazine

[0840]Step 1: (R) -3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-methyl butyrate: to a solution of (R) -4-methyl 2-methylsuccinate (2.2g, 15mmol) and triethylamine (4.54g, 45mmol) in THF (30ml) at 0 deg.C was added isobutyl chloroformate (2.16g, 15.8mmol) dropwise. After stirring for 30 min, 3-chloro-N-hydroxy-benzamidine (2.56g, 15mmol) was added. The reaction mixture was stirred at room temperature for a further 30 minutes and then heated at 135 ℃ with DMF for 45 minutes. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried and concentrated to give 4.0g (95%) (R) -3- [3- (3-chloro-phenyl) - [1, 2, 4]Oxadiazol-5-yl]Methyl-butyrate is a pale yellow oil. Step 2: (R) -3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-butyryl hydrazine: (R) -3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-butyryl hydrazine (430mg, 77%) was prepared by reacting (R) -3- [3- (3-chloro-phenyl) - [1, 2, 4] at 65 ℃]Oxadiazol-5-yl]Methyl butyrate (461.4mg, 2.0mmol) was reacted with hydrazine hydrate (2mL) in methanol (2mL) for 1 hour.¹HNMR(CDCl₃) δ (ppm): 8.07(s, 1H), 7.96(d, 1H), 7.46(m, 2H), 6.98(w, 1H), 3.93(w, 2H), 3.78(m, 1H), 2.86(dd, 1H), 2.55(dd, 1H) and 1.59(d, 3H).

[0841] The following compounds were prepared in a similar manner to example 320:

example No. 2	Name (R)
example No. 2	Name (R)	321	3- [3- (3-chlorophenyl) - [1, 2, 4]]Oxadiazol-5-yl]-3-methylbutyrylhydrazine

[0842] Example 322

[0843]3- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -piperidin-2-one

[0844]1.33ml (3.32mmol) of n-BuLi (2.5M in hexane) are added dropwise at 0 ℃ to a solution of 157mg (1.58mmol) of d-valerolactone in 5, 3ml of THF. After stirring for 2 hours at 0 ℃ 400mg (1.58mmol) of 3-chloromethyl 5- [ 3-chloro-phenyl ] -were added in one portion]-[1，2，4]Oxadiazole and stirring was continued for 3 hours. Addition of NH₄The reaction was quenched with Cl (saturation) and the mixture was quenched with CH₂Cl₂The extraction was performed twice. The combined organic phases were dried and concentrated. Flash chromatography (SiO2, heptane/EtOAc 1: 8) afforded 113mg (25%) of an off-white solid.¹HNMR(CDCl₃)δppm 1.80(m，1H)1.89(m，1H)2.00(m，1H)2.91(m，1H)2.98(m，1H)3.35(m，1H)3.52(m，1H)5.83(s，1H)7.46(t，1H)7.55(d，J＝8.O8Hz，1H)8.00(d，1H)8.11(s，1H)。

[0845] The following compounds were prepared in a similar manner to example 322:

example No. 2	Name (R)
example No. 2	Name (R)	323	3- [5- (5-chloro-2-fluorophenyl) - [1, 2, 4]]Oxadiazol-3-ylmethyl]-piperidin-2-ones

[0846] Example 324

[0847] 3-chloromethyl-5- (5-chloro-thiophen-3-yl) - [1, 2, 4] oxadiazole and 1- [5- (5-chloro-thiophen-3-yl) - [1, 2, 4] oxadiazol-3-ylmethoxy ] -1H-benzotriazole

[0848] A solution of 2-chloro-N-hydroxyacetamidine (781mg, 7.2mmol), 5-chlorothiophene-3-carboxylic acid (1.4g), HBTU (3.55g) and DIPEA (1.3g) in DMF (20ml) was stirred at ambient temperature for 1 hour, after which it was heated at 120 ℃ under argon for 4 hours. The solvent was removed in vacuo and the residue was purified on silica gel chromatography with 0-20% EtOAc in n-heptane to give 38.5mg of the first eluting 3-chloromethyl-5- (5-chloro-thiophen-3-yl) - [1, 2, 4] oxadiazole as a syrup, after which 65mg of the slower eluting 1- [5- (5-chloro-thiophen-3-yl) - [1, 2, 4] oxadiazol-3-ylmethoxy ] -1H-benzotriazole were obtained as a white solid. 3-chloromethyl-5- (5-chloro-thiophen-3-yl) - [1, 2, 4] oxadiazole: 1HNMR (CDCl3) δ (ppm): 8.01(d, 1H), 7.50(d, 1H), 4.63(s, 2H). 1- [5- (5-chloro-thiophen-3-yl) - [1, 2, 4] oxadiazol-3-ylmethoxy ] -1H-benzotriazole: 1HNMR (CDCl3) δ (ppm): 7.97(m, 2H), 7.52(dt, 1H), 7.44(m, 2H), 7.34(m, 1H), 5.70(s, 2H).

[0849] Example 325

[0850] (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -acetonitrile

[0851] 4-methyl-5-thiophen-3-yl-4H- [1, 2, 4] triazole-3-thiol (197mg, 1.0mmol), chloroacetonitrile (95ml, 1.5mmol), sodium carbonate (424mg, 4mmol) and potassium iodide (332mg, 2.0mmol) were stirred together at 100 ℃ for 3 hours, after which 2 hours chloroacetonitrile (60ml, 0.5mmol) was added. After the reaction was cooled, it was diluted with ethyl acetate and washed with water. The organic solution was dried, filtered and evaporated. Chromatography on silica gel (dichloromethane: methanol 19: 1) gives 150mg of the expected compound.

[0852] Example 326

[0853]2- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthio) -propionic acid [0854](R) -2-chloropropionic acid (500mg, 4.6mmol), 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] at room temperature]Triazole-3-thiol (1.09g, 5.58mmol) and potassium carbonate (1.94g, 14.03mmol) were dissolved in acetonitrile (15 ml). After 2.5 hours the reaction was partitioned between ethyl acetate (350ml) and water three times, washed with 1M HCl hydrochloric acid, once with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The reaction was not complete at this stage and the crude product was stirred overnight in DMF (10 ml). The extraction process was repeated and purified by SPE (solid phase extraction) chromatography on silica gel with 300ml ethyl acetate, 100ml, 1% and 100ml 3% formic acid in ethyl acetate to give the title compound (150.7mg, 12%). 1HNMR (CDCl) ₃)δ(ppm)：7.52(dd，2H)，7.19(m，1H)，4.21(q，1H)，3.78(s，3H)，1.64(d，3H)。

[0855] The following compounds were prepared in a similar manner to example 326:

example No. 2	Name (R)
example No. 2	Name (R)	327	2- (4-methyl-5-pyridin-3-yl-4H- [1, 2, 4)]Triazole-3-ylsulfanyl) -propionic acid

[0856] Example 328

[0857]3- (3-chloro-phenyl) -5- (4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0858]The title compound (2.08g, 81.5%) was prepared by reacting 5-chloromethyl-3- (3-chloro-phenyl) - [1, 2, 4] at room temperature]Oxadiazole (1.9g, 8.29mmol) and 4-methyl-4H- [1, 2, 4]Triazole-3-thiol (1.0g, 8.71mmol) and K₂CO₃(4.58g, 33.2mmol) in DMF (19ml) was obtained overnight. 1HNMR (CDCl)₃) δ (ppm): 8.21(s, 1H), 8.05(s, 1H), 7.94(d, 1H), 7.49(d, 1H), 7.43(t, 1H), 4.69(s, 2H) and 3.64(s, 3H).

[0859] Example 329

[0860] {3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl-phenyl ] -carbamic acid tert-butyl ester

[0861]The title compound is prepared by reacting 4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-thiol (53mg, 0.27mmol), 3- (3-chloromethyl- [1, 2, 4)]Oxadiazol-5-yl) -phenyl]Tert-butyl carbamate (75mg, 0.24mmol) and potassium carbonate (101mg, 0.73mmol) in acetonitrile (2.5 ml). Purification by SPE (flash) chromatography using 65% ethyl acetate in hexanes afforded the product (88.0mg, 79%, white solid). 1HNMR (CDCl) ₃)δ(ppm)：8.06(s，1H)，7.73(d，1H)，7.66(d，1H)，7.51(t，2H)，7.42(t，1H)，7.18(m，1H)，6.68(s，1H)，4.51(s，2H)，3.73(s，3H)，1.53(s，9H)。

[0862] The following compounds were prepared in a similar manner to example 41:

example No. 2	Name (R)	¹HNMR	MS
example No. 2	Name (R)	¹HNMR	MS	330	4- (4-cyclopropyl-5- {1- [5- (2, 5-difluoro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.88(d，2H)，7.81(m，1H)，7.75(m，2H)，7.22(m，2H)，5.42(q，1H)，3.22(m，1H)，1.98(d，3H)，1.17(m，2H)，0.79(m，2H)
331	4- (5- {1- [5- (3-methoxy-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.69(m，2H)，7.6(m，1H)，7.52(m，3H)，7.35(t，1H)，7.04(m，1H)，4.93(q，1H)，3.78(t，3H)，3.55(s，3H)，1.86(d，3H)		330
331				332	4- { 4-methyl-5- [1- (5-m-tolyl- [1, 2, 4 ]]Oxadiazole) ethylthio group]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.71(m，2H)，7.82(m，2H)，7.53(m，2H)，7.32(m，2H)，4.94(q，1H)，3.54(s，3H)，2.33(s，3H)，1.87(d，3H)
333	5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -3-o-tolyl- [1, 2, 4]Oxadiazoles as herbicides	2.58(s，3H)3.70(s，3H)4.65(s，2H)7.17(s，1H)7.29(s，2H)7.36(s，1H)7.46(s，1H)7.51(s，1H)7.90(s，1H)	370.0	332
333			370.0	334	5- (3-chloro-phenyl) -3- (4-cyclopropyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	0.87(m，2H)1.18(m，2H)3.47(ddd，J＝6.95，3.41，3.28Hz，1H)4.70(s，2H)7.23(m，1H)7.67(m，2H)7.77(m，2H)8.04(d，2H)	415.9

335	2- {3- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-5-thiophen-2-yl- [1, 2, 4]Triazol-4-yl } -ethanol	2.36(s，3H)4.03(t，2H)4.30(t，2H)4.57(s，2H)7.11(m，2H)7.35(s，1H)7.47(d，1H)7.64(d，1H)7.81(d，1H)	417.9
335			417.9	336	4- { 4-Ethyl-5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4H-[1，2，4]Triazol-3-yl } -pyrimidines	1.38(t，3H)2.34(s，3H)4.66(m，4H)7.19(m，1H)7.47(m，1H)7.83(d，1H)8.23(d，1H)8.94(d，1H)9.28(s，1H)	398.0
337	3- (4-Ethyl-5-furan-3-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	1.34(t，3H)2.37(s，3H)4.06(q，2H)4.61(s，2H)6.82(s，1H)7.12(m，1H)7.36(ddd，1H)7.55(s，1H)7.85(d，2H).	386.0	336			398.0
337			386.0	338	{3- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio ]-5-thiophen-2-yl- [1, 2, 4]Triazol-4-yl } -acetic acid methyl ester	2.36(s，3H)3.70(s，3H)4.46(s，2H)5.10(s，2H)7.21(m，2H)7.47(m，2H)7.73(d，1H)7.86(m，1H)	445.9
339	5- (2-fluoro-5-methylphenyl) -3- [ 5-furan-2-yl-4- (2-methoxy-ethyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	2.26(s，3H)3.16(s，3H)3.57(t，2H)4.42(t，2H)4.44(s，2H)6.60(s，1H)7.10(m，2H)7.37(m，1H)7.70(s，1H)7.73(d，1H)	416.0	338			445.9

340	3- (4-cyclopropyl-5-furan-2-radical-4H- [1, 2, 4]Triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	0.87(m，2H)1.14(m，2H)2.35(s，3H)3.39(dt，1H)4.71(s，2H)6.72(s，1H)7.09(d，1H)7.39(m，1H)7.56(m，1H)7.87(d，1H)7.93(s，1H)	398.0
340			398.0	341	3- (5-chloro-2-fluoro-phenyl) -5- (4-cyclopropylmethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	0.32(m，2H)0.56(m，2H)1.14(d，1H)4.00(d，2H)4.76(s，2H)7.16(ddd，2H)7.43(m，1H)7.50(t，2H)7.99(dd，1H)	448.1
342	4- {5- [3- (5-chloro-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-5-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyrimidines	1.40(t，3 H)4.63(q，2H)4.72(s，2)7.20(m，1H)7.53(m，1H)8.06(dd，1H)8.29(d，1H)8.86(d，1H)9.26(s，1H).	417.8	341			448.1
342			417.8	343	3- (5-cyclopentyl-4-ethyl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazoles as herbicides	1.29(t，3H)1.66(m，3H)1.87(m，2H)2.02(m，3H)2.42(s，3H)3.01(s，2H)3.90(d，2H)4.52(s，2H)7.39(d，2H)7.90(d，2H)	370.2
344	3- (3-chloro-phenyl) -5- { 4-ethyl-5- [2- (4-methoxy-phenyl) -ethyl]-4H-[1，2，4]Triazol-3-ylthiomethyl } - [1, 2, 4]Oxadiazoles as herbicides	1.18(t，3H)2.95(t，2H)3.09(t，2H)3.72(q，2H)3.76(s，3H)4.66(s，2H)6.81(d，2H)7.09(d，2H)7.40(t，1H)7.47(m，1H)7.92(d，1H)8.03(s，1H)	456.1	343			370.2

345	5- (3-chloro-phenyl) -3- (4-ethyl-5-p-tolyloxymethyl-4H- [1, 2, 4%]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	1.23(t，3H)2.22(s，3H)4.02(d，2H)4.60(s，2H)5.22(s，2H)6.92(d，2H)7.09(d，2H)7.65(t，1H)7.79(d，1H)8.04(m，2H)	442.1
345			442.1	346	5- (3-chloro-phenyl) -3- [4- (2-methoxy-ethyl) -5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	3.14(s，3H)3.57(t，2H)4.30(t，2H)4.58(s，2H)7.23(m，1H)7.64(m，2H)7.78(m，2H)8.03(d，2H)	433.9
347	3- (5-chloro-2-fluoro-phenyl) -5- (4-ethyl-5-methoxymethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4 ]Oxadiazoles as herbicides	7.98(m, 1H), 7.43(m, 1H), 7.16 (significant t, 1H), 4.73(s, 2H), 4.62(s, 2H), 4.01(q, 2H), 3.33(s, 3H), 1.34(t, 3H).	384.9	346			433.9
347			384.9	348	5- (5-chloro-2-fluoro-phenyl) -3- (4-ethyl-5-methoxymethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.05(m, 1H), 7.53(m, 1H), 7.21 (overt t, 1H); 4.62(s, 2H), 4.61(s, 2H), 4.02(q, 2H), 3.34(s, 3H), 1.32(t, 3H).	384.9
349	5- (3-chloro-phenyl) -3- (4-ethyl-5-methoxymethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.07 (sensibly s, 1H), 7.97(m, 1H), 7.55 (m, 1H), 7.45 (sensibly t, 1H), 4.62(s, 2H), 4.59(s, 2H), 4.01(q, 2H), 3.34(s, 3H), 1.32(t, 3H).	366.9	348			384.9

350	3- (3-chloro-phenyl) -5- (4-ethyl-5-methoxymethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.02(m, 1H), 7.92(m, 1H), 7.46(m, 1H), 7.39 (overt t, 1H), 4.71(s, 2H), 4.62(s, 2H), 4.01(q, 2H), 3.34(s, 3H), 1.34(t, 3H).	366.9
350			366.9	351	4- (5- {1- [3- (3-chloro-phenyl) -isoxazol-5-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	1.82(d，3H)，3.46(s，3H)，4.93(q，1H)，6.33(s，1H)，7.23-7.31(m，2H)，7.44(d，2H)，7.49(m，1H)，7.61(s，1H)，8.63(d，2H).	399.1
352	3- (4-allyl-5-furan-2-yl-4H- [1, 2, 4) ]Triazol-3-ylsulfanylmethyl) -5- (3-chloro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	4.6(s，2H)，4.8(d，2H)，5.0(d，1H)，5.2(d，1H)，5.9(m，1H)，6.5(m，1H)，7.1(d，1H)，7.4(t，1H)，7.5(m，2H)，8.0(d，1H)，8.1(s，1H)	399.95	351			399.1
352			399.95	353	3- (4-allyl-5-furan-2-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -5-thiophen-3-yl- [1, 2, 4]Oxadiazoles as herbicides	4.5(s，2H)4.8(d，2H)5.0(d，1H)5.2(d，1H)5.9(m，1H)6.5(m，1H)7.0(d，1H)7.4(m，1H)7.5(s，1H)7.6(d，1H)8.2(m，1H)	371.98
354	5- (4-allyl-5-furan-2-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -3-furan-2-yl- [1, 2, 4]Oxadiazoles as herbicides	4.7(s，2H)4.8(m，2H)5.0(d，1H)5.2(d，1H)5.9(m，1H)6.5(dt，2H)7.1(dd，2H)7.6(dd，2H)	356.01	353			371.98

355	5- (3-chloro-phenyl) -3- [ 4-ethyl 5- (4-methoxy-phenoxymethyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	1.4(t，3H)3.7(s，3H)4.1(q，2H)4.6(s，2H)5.2(s，2H)6.8(d，2H)6.9(d，2H)7.4(t，1H)7.6(d，1H)8.0(d，1H)8.1(s，1H)	457.91
355			457.91	356	3- (3-chloro-phenyl) -5- [ 4-ethyl-5- (4-methoxy-phenoxymethyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	1.4(t，3H)3.7(s，3H)4.1(q，2H)4.8(s，2H)5.2(s，2H)6.8(d，2H)6.9(d，2H)7.4(t，1H)7.5(m，1H)7.9(d，1H)8.0(s，1H)	457.97
357	{5- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -methanol	1.4(t，3H)4.2(d，2H)4.7(s，2H)4.9(s，2H)7.4(t，1H)7.5(m，1H)7.9(d，1H)8.0(s，1H)	352.09	356			457.97
357			352.09	358	3- (3-chloro-phenyl) -5- [ 4-ethyl-5- (2-methoxy-ethyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	1.3(t，3H)3.0(t，2H)3.3(s，3H)3.8(t，2H)3.9(q，2H)4.7(s，2H)7.4(t，1H)7.5(ddd，1H)7.9(dt，1H)8.0(t，1H)	380.12
359	3- (3-chloro-phenyl) -5- [ 4-ethyl-5-methylthiomethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	1.4(t，3H)2.1(s，3H)3.8(s，2H)4.0(q，2H)4.7(s，2H)7.4(t，1H)7.5(ddd，1H)7.9(dt，1H)8.0(t，1H)	382.07	358			380.12

360	3- (3-chloro-phenyl) -5- (5-ethoxymethyl-4-ethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	2(t，3H)1.3(t，3H)3.5(q，2H)4.0(q，2H)4.7(s，2H)4.7(s，2H)7.4(t，1H)7.5(ddd，1H)7.9(dt，1H)8.0(t，1H)	379.13
360			379.13	361	5- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazole-3-carboxylic acid methyl ester
362	2- (5-chloro-2-fluoro-phenyl) -5- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4 ]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazoles as herbicides	1.4(t 3H)4.2(q，2H)4.7(s，2 H)6.6(dd，1H)7.1(d，1H)7.2(m，1H)7.5(ddd，1H)7.6(d，1H)8.0(dd，1H)	406.07	361
362			406.07	363	2- (3-chloro-phenyl) -5- (4-cyclopropyl-5-furan-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazoles as herbicides	0.9(m，2H)1.2(m，2H)3.2(m，1H)4.8(s，2H)6.6(m，1H)7.0(d，1H)7.4(t，1H)7.5(m，1H)7.6(m，1H)7.9(m，1H)8.0(m，1H)	399.86

364	5- (3-chloro-phenyl) -3- {1- [ 4-ethyl-5- (tetrahydro-furan-2-yl) -4H- [1, 2, 4]Triazol-3-ylthio]-ethyl } - [1, 2, 4]Oxadiazoles as herbicides	1.3(t，3H)1.9(d，3H)2.0(m，1H)2.1(m，1H)2.3(m，1H)2.8(m，1H)3.8(m，2H)4.0(m，1H)4.1(m，1H)5.0(m，1H)5.1(m，1H)7.4(t，1H)7.6(m，1H)8.0(m，1H)8.1(s，1H)	406.04
364			406.04	365	4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -pyridazines	1.4(t，3H)1.9(d，3H)4.1(m，2H)5.2(q，1H)7.4(t，1H)7.5(m，1H)7.8(m，1H)8.0(m，1H)8.1(m，1H)9.4(m，1H)9.5(s，1H)	414.12
366	4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-ylmethyl) -pyridine	1.0(t，3H)1.9(d，3H)3.7(m，2H)4.2(m，2H)5.0(q，1H)7.1(m，2H)7.4(t，1H)7.5(m，1H)7.9(d，1H)8.1(s，1H)8.5(m，2H)	427.06	365			414.12
366			427.06	367	5- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -pyridin-2-ols	1.3(t，3H)1.9(d，3H)3.9(m，2H)5.1(q，1H)6.7(d，1H)7.5(t，1H)7.6(m，1H)7.7(m，1H)7.7(s，1H)8.0(d，1H)8.1(s，1H)13.1(s，1H)	429.1
368	4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -phenols	1.2(t，3H)1.9(d，3H)3.9(q，2H)5.1(q，1H)6.9(d，2H)7.3(d，2H)7.4(t，1H)7.5(m，1H)7.9(m，1H)8.1(m，1H)10.2(s，1H)	428.08	367			429.1

369	5- (3-chloro-phenyl) -3- [5- (4-methoxy-phenoxymethyl) -4- (tetrahydro-furan-2-ylmethyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	1.54(m，1H)1.86(m，2H)2.02(m，1H)3.71(m，4H)3.79(m，1H)4.13(m，3H)4.60(m，2H)5.30(s，2H)6.82(m，2H)6.92(m，2H)7.44(t，1H)7.55(d，1H)7.95(d，1H)8.07(s，1H)
369				370	5- (3-chloro-phenyl) -3- [ 4-cyclopropyl-5- (4-methoxy-phenoxymethyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	1.14(m，4H)3.10(s，1H)3.75(s，3H)4.70(s，2H)5.21(s，2H)6.82(d，2H)6.95(d，2H)7.45(t，1H)7.56(m，1H)7.99(d，1H)8.10(s，1H)
371	5- (5-chloro-2-fluoro-phenyl) -3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4 ]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	1.38(t，3H)4.27(q，2H)4.64(s，2H)6.58(m，1H)7.21(m，2H)7.53(m，1H)7.59(m，1H)8.06(m，1H)		370
371				372	3- (4-ethyl-5-methoxymethyl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazoles as herbicides	1.29(t，3H)2.40(s，3H)3.31(s，3H)3.99(m，2H)4.56(s，2H)4.60(s，2H)7.37(m，2H)7.87(m，2H)	346
373	3- [ 4-Ethyl-5- (tetrahydro-furan-2-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-5-m-tolyl- [1, 2, 4]Oxadiazoles as herbicides	1.30(t，3H)1.97(m，1H)2.10(m，1H)2.24(m，1H)2.39(s，3H)2.80(m，1H)3.79(m，1H)3.86(m，1H)3.99(m，1H)4.08(m，1H)4.54(m，2H)4.98(m，1H)7.36(m，2H)7.86(m，1H)7.88(s，1H)	372	372			346

374	2- (3-chloro-phenyl) -5- {1- [ 4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4]Triazol-3-ylthio]-ethyl } - [1, 3, 4]Oxadiazoles as herbicides	1.18(m，3H)1.95(d，3H)3.81(s，3H)3.90(q，2H)5.15(q，1H)6.94(m，2H)7.35(m，1H)7.45(m，3H)7.81(m，1H)7.92(m，1H)
374				375	4- {5- [3- (2, 5-difluoro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyrimidines	1.43(t，3H)，4.64(q，2H)，4.87(s，2H)，7.18(m，2H)，7.72(m，1H)，8.29(dd，1H)，8.89(d，1H)，9.30(d，1H)	402.1
376	4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyrimidines	4.12(s，3H)，4.64(s，2H)，7.21(t，1H)，7.57(m，1H)，8.06(dd，1H)，8.28(dd，1H)，8.92(d，1H)，9.30(d，1H)	404.1	375			402.1
376			404.1	377	3- (3-chloro-phenyl) -5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.03(s，1H)，7.92(d，1H)，7.53(d，1H)，7.48(m，2H)，7.40(t，1H)，7.18(t，1H)，4.87(s，2H)，3.72(s，3H).	390.96
378	5- (3-methylthiophenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	7.92(s，1H)，7.84(d，1H)，7.53(m，2H)，7.43(m，2H)，7.18(m，1H)，4.53(s，2H)，3.73(s，3H)，2.52(s，3H).		377			390.96

379	2- [5- (3-methylsulfanyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-1H-benzimidazole
379				380	5- (2, 5-dimethyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	7.87(s，1H)，7.49(m，2H)，7.22(m，3H)，4.56(d，2H)，3.74(s，3H)，2.61(s，3H)，2.37(s，3H).
381	5- (2-fluoro-5-methyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	7.83(dd，1H)，7.49(m，2H)，7.35(m，1H)，7.16(m，2H)，4.53(s，2H)，3.73(s，3H)，2.35(s，3H).	388.10	380
381			388.10	382	5- (3-cyclopropyl-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	7.87(d，1H)，7.79(s，1H)，7.51(m，2H)，7.40(t，1H)，7.30(m，1H)，7.20(m，1H)，4.53(s，2H)，3.73(s，3H)，1.96(m，1H)，1.04(m，2H)，0.77(m，2H).
383	4- {5- [2 (3-chloro-phenyl) -oxazol-4-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.80(d，2H)，8.02(dd，1H)，7.88(dd，1H)，7.80(s，1H)，7.60(d，2H)，7.42(m，2H)，4.51(s，2H)，3.64(s，3H).		382

384	4- [ 4-methyl-5- (5-thiophen-2-yl- [1, 2, 4 ]]Oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4]Triazol-3-yl]-pyridine	8.82(bs，2H)，7.90(m，1H)，7.66(m，3H)，7.22(m，1H)，4.58(s，2H)，3.73(s，3H).
384			385	4- { 4-methyl-5- [5- (3-methylsulfanyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.81(m，2H)，7.95(s，1H)，7.86(m，1H)，7.64(m，2H)，7.45(m，2H)，4.63(s，2H)，3.72(s，3H)，2.55(3H).
386	4- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.83(d，2H)，8.11(s，1H)，8.00(d，1H)，7.64(m，2H)，7.60(m，1H)，7.49(t，1H)，4.64(s，2H)，3.73(s，3H).	385
386			387	2-methyl-4- [3- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4-]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-pyridine	8.82(d，2H)，8.74(d，1H)，7.82(s，1H)，7.76(d，1H)，7.64(d，2H)，4.68(s，2H)，3.74(s，3H)，2.68(s，3H).
388	1- {3[3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-phenyl } -ethanone	8.67(s，1H)，8.29(d，1H)8.20(d，1H)，7.68(t，1H)，7.52(m，2H)，7.20(m，1H)，4.58(s，2H)，3.76(s，3H)，2.68(s，3H).	387
388			389	4- {5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.81(dd，2H)，7.86(d，1H)，7.64(m，2H)，7.39(m，1H)，7.14(dd，1H)，4.63(s，2H)，3.73(s，3H)，2.39(s，3H).	383.09

390	2-methyl-4- [ 4-methyl-5- (5-m-tolyl- [1, 2, 4 ] ]Oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4]Triazole compounds-3-yl]-pyridine	8.68(dd，1H)，7.92(m，2H)，7.52(bs，1H)，7.4(m，3H)，4.61(s，2H)，3.7(s，3H)，2.67(s，3H)，2.44(s，3913H).
390			391	3- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole compounds	7.76(s，1H)，7.68(m，1H)，7.54(m，1H)，7.48(m，1H)，7.40(m，2H)，7.20(m，1H)，6.76(s，1H)，4.56(s，2H)，3.70(s，3H).
392	4- {5- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.82(m，2H)，7.76(m，1H)，7.65(m， 3H)，7.41(m，2H)，6.77(s，1H)，4.61(s，2H)，3.69(s，3H).	391
392			393	3- (4-butyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (3-chloro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	8.07(s，1H)，7.95(dd，1H)，7.48(m，4H)，7.17(dd，1H)，4.59(s，2H)，4.05(t，2H)，1.67(m，2H)，1.30(m，2H)，0.88(t，3H).
394	5- (3-chloro-phenyl) -3- [4- (3-methoxy-propyl) -5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.01(d，1H)，7.91(dd，1H)，7.48(m，4H)，7.12(m，1H)，4.51(s，2H)，4.17(t，2H)，3.34(t，2H)，3.18(s，3H)，1.90(m，2H).	393

395	3- (4-benzyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (3-chloro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	8.09(s，1H)，7.97(dd，1H)，7.57(m，1H)，7.47(m，，2H)，7.24(m，，4H)，7.06(m，3H)，5.37(s，2H)，4.57(s，2H).
395			396	5- (3-chloro-phenyl) -3- (4-furan-2-ylmethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.10(d，1H)，8.03(dd，1H)，7.55(m，4H)，7.38(s，1H)，7.20(dd，1H)，6.32(m，2H)，5.30(s，2H)，4.60(s，2H).	457.02
397	3- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.93(m，1H)，8.78(m，1H)，8.03(m，3H)，7.59(m，1H)，7.51(m，2H)，4.63(s，2H)，3.69(s，3H).	396			457.02
397			398	5- (3-chloro-phenyl) -3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.11(m，1H)，8.05(m，1H)，7.74 (m，1H)，7.59(m，1H)，7.51(m，3H)，4.57(s，2H)，3.71(s，3H).
399	4- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -2-methyl-pyridine	8.69(d，1H)，8.10(s，1H)，8.00(m，1H)，7.49(m，4H)，4.63(s，2H)，3.71(s，3H)，2.67(s，3H).	398
399			400	5- (5-chloro-2-fluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4 ]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.08(m，1H)，7.51(m，1H)7.21(m，1H)，4.59(s，2H)，3.77(s，3H).	409.00

401	4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.82(d，2H)，8.08(m，1H)8.29(d，1H)，7.64(d，2H)，7.56(m，1H)，7.24(t，1H)，4.66(s，2H)，3.75(s，3H).	404.07
401			404.07	402	3- {5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.92(s，1H)，8.76(d，1H)，8.07(d，1H)，7.87(d，1H)，7.36(m，3H)，4.59(s，2H)，3.69(s，3H)，2.39(s，3H).
403	5- (3-chloro-phenyl) -3- (5-thiophen-2-yl-4-thiophen-2-ylmethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	(CD3OD as solvent): 8.05(m, 1H), 8.00(dd, 1H), 7.75(dd, 1H), 7.58(m, 1H), 7.54(m, 1H), 7.53(m, 1H), 7.26(m, 1H), 7.22(m, 1H), 6.86(m, 2H), 5.63(s, 2H), 4.51(s, 2H).		402
403				404	5- (3-chloro-phenyl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	(CD3OD as solvent): 8.08(m, 1H), 8.07(dd, 1H), 7.75(m, 1H), 7.67(m, 1H), 7.60(m, 2H), 7.28(dd, 1H), 4.57(s, 2H), 4.27(m, 2H), 1.29(m, 3H).	405.10
405	3- {5- [3- (2-fluoro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-5-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.90(m，1H)，8.77(dd，1H)，8.03 (m，1H)，7.78(m，1H)，7.48(m，1H)，7.28(m，1H)，7.12(m，1H)，4.73(s，2H)，3.68(s，3H)，2.36(s，3H).		404			405.10

406	4- {5- [3- (2-fluoro-5-methyl-phenyl) - [1, 2, 4%]Oxadiazol-5-ylmethylthio ]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.81(m，2H)，7.77(m，1H)，7.62(m，2H)，7.31(m，1H)，7.11(dd，1H)，4.75(s，2H)，3.72(s，3H)，2.37(s，3H).
406			407	4- {5- [5- (5-bromo-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.82(m，2H)，8.23(m，1H)，7.71(m，2H)，7.65(m，1H)，7.18(d，1H)，4.66(s，2H)，3.75(s，3H).	448.02
408	3- {5- [5- (5-bromo-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.92(m，1H)，8.76(m，1H)，8.22 (m，1H)，8.05(m，1H)，7.50(m，1H)，7.4(m，1H)，7.17(dd，1H)，4.63(s，2H)，3.70(s，3H).	407			448.02
408			409	5- (5-bromo-2-fluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.23(dd，1H)，7.70(m，1H)，7.52(m，2H)，7.19(m，2H)，4.49(s，2H)，3.77(s，3H).	452.90
410	5- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -3-phenyl [1, 2, 4]Oxadiazoles as herbicides	8.06(d，2H)7.34(d，1H)，7.51(m，5H)，4.68(s，2H)，3.68(s，3H).	409			452.90
410		8.06(d，2H)7.34(d，1H)，7.51(m，5H)，4.68(s，2H)，3.68(s，3H).	411	3- {5- [5- (3-fluoro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.92(s，1H)，8.78(d，1H)8.05(d，1H)，7.93(d，1H)，7.91(d，1H)，7.50(m，2H)，7.28(t，1H)，4.64(s，2H)，3.70(s，3H).

412	4- {5- [5- (3-fluoro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.82(d，2H)，7.93(d，1H)7.90(d，1H)，7.64(d，2H)，7.52(m，1H)，7.33(m，1H)，4.64(s，2H)，3.73(s，3H).
412			413	5- (3-fluoro-phenyl) -3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	7.90(d，1H)7.82(d，1H)，7.74(d，1H)，7.51(m，3H)，4.58(s，2H)，3.71(s，3H).
414	3- [ 4-methyl-5- (5-thiophen-3-yl- [1, 2, 4 ]]Oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4]Triazol-3-yl]-pyridine	8.91(s，1H)，8.78(d，1H)8.23(d，1H)，8.04(d，1H)，7.66(d，1H)，7.49(m，2H)4.60(s，2H)，3.69(s，3H).	413
414			415	3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -5-thiophen-3-yl- [1, 2, 4]Oxadiazoles as herbicides	8.22(d，1H)7.74(d，1H)，7.63(d，1H)，7.49(m，3H)，4.54(s，2H)，3.70(s，3H).
416	2-chloro-4- [3- (4-methyl-5-pyridin-3-yl-4H- [1, 2, 4- ]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-pyridine	8.92(s，1H)，8.78(d，1H)8.65(d，1H)，8.04(t，2H)，7.89(d，1H)，7.51(m，1H)，4.69(s，2H)，3.71(s，3H).	415
416			417	2-chloro-4- [3- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4-]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-pyridine	8.82(d，2H)，8.65(d，1H)8.02(s，1H)，7.89(d，1H)，7.64(d，2H)，4.70(s，2H)，3.74(s，3H).

418	2-chloro-4- [3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-pyridine	8.64(d，1H)8.01(s，1H)，7.88(d， 1H)，7.75(d，1H)，7.52 (m，2H)，4.62(s，2H)，3.72(s，3H).
418				419	4- [ 4-methyl-5- (5-phenyl- [1, 2, 4 ]]Oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4]Triazol-3-yl]-pyridine	8.82(d，2H)，8.12(d，2H)7.63(m，3H)，7.55(m，2H)，4.63(s，2H)，3.72(s，3H).
420	3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-phenyl- [1, 2, 4]Oxadiazoles as herbicides	8.11(d，2H)7.74(d，1H)，7.57(m，1H)，7.52(m，4H)，4.56(s，2H)，3.70(s，3H).		419
420				421	5- (5-bromo-2-fluoro-phenyl) -3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	(CD3OD as solvent): 8.21(m, 1H), 8.02(m, 1H), 7.82(m, 1H), 7.68(m, 1H), 7.56(m, 1H), 7.33(t, 1H), 4.50(s, 2H), 3.82(s, 3H).
422	3- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole compounds	(CD3OD as solvent): 7.84(s, 1H), 7.75(m, 2H), 7.60(m, 1H), 7.50(m, 2H), 7.27(m, 1H), 6.92(s, 1H), 4.51(s, 2H), 4.23(q, 2H), 1.33(t, 3H).	404.05	421
422			404.05	423	2-chloro-4- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4 ] ]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-pyridine	8.64(d，1H)，8.01(s，1H)7.98(d，1H)，7.54(d，1H)，7.50(d，1H)，7.20(m，1H)，4.61(s，2H)，3.76(s，3H).	392.00

424	4- {5- [3- (3-fluoro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.83(d，2H)，7.85(d，1H)7.78(d，1H)，7.62(d，2H)，7.46(m，1H)，7.22(m，1H)，4.76(s，2H)，3.72(s，3H).
424				425	3- (3-fluoro-phenyl) -5- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	7.84(d，1H)7.74(m，1H)，7.51(m，3H)，7.24(m，1H)，4.70(s，2H)，3.70(s，3H).
426	3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazoles as herbicides	(CD3OD as solvent): 7.89(m, 2H), 7.76(m, 1H), 7.60(m, 1H), 7.47(m, 2H), 7.27(m, 1H), 4.55(s, 2H), 4.25(q, 2H), 2.41(s, 3H), 1.32(s, 3H)	384.13	425
426			384.13	427	3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	(CD3OD as solvent): 7.85 (m, 1H), 7.75(m, 1H), 7.60(m, 1H), 7.55(m, 1H), 7.27(m, 1H), 7.22(m, 1H), 4.57(s, 2H), 4.27(q, 2H), 2.36(s, 3H), 1.33(s, 3H).	402.09
428	4- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-furan-2-ylmethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	(CD3OD as solvent): 8.75(m, 2H), 8.04(m, 2H), 7.78(m, 2H), 7.66(m, 1H), 7.60(m, 1H), 7.37(m, 1H), 6.30(m, 2H), 5.42(s, 2H), 4.56(s, 2H).	452.10	427			402.09

429	4- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.80(m，2H)，8.09(m，1H)，7.98(m，1H)，7.58(m，3H)，7.50(dd，1H)，4.69(s，2H)，4.12(m，2H)，1.36(m，3H).
429				430	3- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	(CD3OD as solvent): 8.87(s, 1H), 8.77(d, 1H), 8.07(m, 3H), 7.67(m, 2H), 7.61(dd, 1H), 4.62(s, 2H), 4.13(m, 2H), 1.26(m, 3H).	400.12
431	5- (3-chloro-phenyl) -3- (4-ethyl-5-thiophen-3-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	(CD3OD as solvent): 7.79(m, 3H), 7.67(m, 2H), 7.51(m, 2H), 4.56(s, 2H), 4.22(q, 2H), 1.30(t, 3H).	405.07	430			400.12
431			405.07	432	3- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-furan-2-ylmethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	(CD3OD as solvent): 8.86(s, 1H), 8.76(d, 1H), 8.07(m, 1H), 8.01(m, 2H), 7.64(m, 3H), 7.36(s, 1H), 6.29(s, 2H), 5.37(s, 2H), 4.55(s, 2H).	452.12
433	3- (4-furan-2-ylmethyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazoles as herbicides	(CD3OD as solvent): 7.87(m, 2H), 7.73(m, 1H), 7.63(m, 1H), 7.45(m, 3H), 7.25(m, 1H), 6.31(m, 2H), 5.42(s, 2H), 4.49(s, 2H), 2.40(s, 3H).	436.16	432			452.12

434	5- (5-fluoro-2-methyl-phenyl) -3- (4-furan-2-ylmethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	(CD3OD as solvent): 7.75(dd, 1H), 7.69(m, 1H), 7.66(m, 1H), 7.41(m, 1H), 7.38(m, 1H), 7.25(m, 2H), 6.32(s, 2H), 5.44(s, 2H), 4.51(s, 2H), 2.36(s, 3H).	454.12
434			454.12	435	5- (3-chloro-phenyl) -3- (4-furan-2-ylmethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.23(s，1H)，8.09(m，1H)，7.97(m，1H)，7.48(m，1H)，7.45(m，1H)，7.37(s，1H)，6.39(m，1H)，6.34(m，1H)，5.12(s，2H)，4.55(s，2H).	375.09
436	3- [3- (4-methyl-5-pyridin-3-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-benzonitrile	8.92(s，1H)，8.78(d，1H)8.43(s，1H)，8.35(d，1H)，8.05(d，1H)，7.91(d，1H)，7.72(t，1H)，7.52(m，1H)，4.67(s，2H)，3.71(s，3H).	376.20	435			375.09
436			376.20	437	3- [3- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-benzonitrile	8.82(d，2H)，8.43(s，1H)8.35(d，1H)，7.90(t，1H)，7.64(d，2H)，4.68(s，2H)，3.74(s，3H).	376.10
438	3- [3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-benzonitrile	8.42(s，1H)，8.35(d，1H)7.89(d，1H)，7.72(m，2H)，7.52(s，1H)，4.61(s，2H)，3.73(s，3H).		437			376.10

439	5- (5-chloro-2-fluoro-phenyl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.08(m，1H)，7.54(m，2H)，7.48(d，1H)，7.20(m，2H)，4.69(s，2H)，4.18(m，2H)，1.39(t，3H).	423.12
439			423.12	440	2-chloro-4- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-pyridine	8.64(d，1H)，8.02(s，1H)，7.89(d，1H)，7.53(d，1H)，7.48(d，1H)，7.20(t，1H)，4.69(s，2H)，4.17(m，2H)，1.40(t，3H).	406.00
441	3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -5-thiophen-3-yl- [1, 2, 4 ]Oxadiazoles as herbicides	8.23(s，1H)，7.66(d，1H)，7.53(d，1H)，7.48(m，2H)，7.19(t，1H)，4.63(s，2H)，4.17(m，2H)，1.40(t，3H).	376.10	440			406.00
441			376.10	442	3- (4-ethyl-5-thiophen-3-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazoles as herbicides	7.93(m，2H)，7.71(m，1H)，7.49(m，2H)，7.42(m，2H)，4.63(s，2H)，4.10(q，2H)，2.43(s，3H)，1.36(t，3H).	384.10
443	4- [ 4-Ethyl-5- (5-m-tolyl- [1, 2, 4 ]]Oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4]Triazol-3-yl]-pyridine	8.80(m，2H)，7.91(m，2H)，7.60(m，2H)，7.41(m，2H)，4.68(s，2H)，4.09(m，2H)，2.43(s，3H)，1.29(s，3H).	379.20	442			384.10

444	3- [ 4-Ethyl-5- (5-m-methyl)Phenyl- [1, 2, 4 ]]Oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4]Triazol-3-yl]-pyridine	(CD3OD as solvent): 8.87(s, 1H), 8.77(d, 1H), 8.02(m, 1H), 7.92(m, 2H), 7.49(m, 1H), 7.42(m, 2H), 4.67(s, 2H), 4.05(q, 2H), 2.43(s, 3H), 1.35(t, 3H).	379.20
444			379.20	445	3- (4-ethyl-5-thiophen-3-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	7.88(dd，1H)，7.71(m，1H)，7.49(m，2H)，7.28(m，1H)，7.14(dd，1H)，4.66(s，2H)，4.11(q，2H)，2.39(s，3H)，1.34(t，3H).
446	4- { 4-Ethyl-5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.80(m，2H)，7.86(m，1H)，7.60(m，2H)，7.38(m，1H)，7.14(dd，1H)，4.70(s，2H)，4.11(q，2H)，2.39(s，3H)，1.36(t，3H).	398.20	445
446			398.20	447	3- { 4-Ethyl-5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2,]4 oxadiazol-3-ylMethylthio group]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.87(s，1H)，8.76(d，1H)，8.01(m，1H)，7.88(m，1H)，7.49(m，1H)，7.28(m，1H)，7.14(dd，1H)，4.69(s，2H)，4.07(q，2H)，2.39(q，2H)，1.35(t，3H).
448	3- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-5-pyridin-4-yl- [1, 2, 4]Triazol-4-ylamines	(DMSO-D6 as solvent): 8.75(dd, 2H), 8.05(m, 4H), 7.79(m, 1H), 7.66(dd, 1H), 6.33(s, 2H), 4.65(s, 2H).	387.05	447

449	4- {5- [5- (5-bromo-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-3-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.81(dd，2H)，8.24(m，1H)，7.71(m，1H)，7.61(m，2H)，7.18(dd，1H)，4.72(s，2H)，4.13(m，2H)，1.29(m，3H).	464.02
449			464.02	450	5- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -3-thiophen-2-yl- [1, 2, 4]Oxadiazoles as herbicides	7.75(m，2H)，7.51(m，3H)，7.16(m，1H)，4.64(s，2H)，3.70(s，3H).
451	3- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-benzonitrile	8.42(s，1H)，8.35(d，1H)，7.89(d，1H)，7.71(t，1H)，7.54(d，1H)，7.48(d，1H)，7.20(t，1H)，4.68(s，2H)，4.16(m，2H)，1.40(t，3H).	395.10	450		7.75(m，2H)，7.51(m，3H)，7.16(m，1H)，4.64(s，2H)，3.70(s，3H).
451			395.10	452	3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-phenyl- [1, 2, 4]Oxadiazoles as herbicides	8.13(d，2H)，7.49(brm，5H)，7.20(m，1H)，4.65(s，2H)，4.16(m，2H)，1.40(t，3H).	370.09
453	4- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-2-methoxy-pyridine	8.36(d，1H)，7.51(brm，3H)，7.42(s，1H)，7.19(m，1H)，4.68(s，2H)，4.16(m，2H)，1.42(t，3H).		452			370.09
453				454	3- (3-chloro-phenyl) -5- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.06(s，1H)，7.95(d，1H)，7.54(m，1H)，7.49(m，1H)，7.42(m，2H)，7.20(m，1H)，4.78(s，2H)，4.17(q，2H)，1.41(t，3H).

455	4- {5- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.82(m，2H)，7.76(m，1H)，7.66(m，1H)，7.60(m，2H)，7.41(m，2H)，6.78(s，1H)，4.65(s，2H)，4.07(q，2H)，1.40(t，3H).	399.10
455			399.10	456	2-methyl-4- [3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-pyridine	8.73(d，1H)，7.81(s，1H)，7.75(s，2H)，7.51(m，2H)，4.60(s，2H)，3.71(s，3H)2.68(s，3H).
457	4- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-2-methyl-pyridine	8.73(d，1H)，7.82(s，1H)，7.76(d，1H)，7.54(d，1H)，7.48(d，1H)，7.29(m，1H)，4.68(s，2H)，4.16(m，2H)，2.68(s，3H)，1.41(t，3H).		456
457				458	5- (4-Ethyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) -3-thiophen-2-yl- [1, 2, 4 ]Oxadiazoles as herbicides	7.78(d，1H)，7.53(t，2H)，7.48(d，1H)，7.18(m，2H)，4.74(s，2H)，4.17(m，2H)，1.41(t，3H).	376.00
459	4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-3-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.82(d，2H)，8.09(m，1H)，7.58(m，3H)，7.24(m，1H)，4.73(s，2H)，4.13(m，2H)，1.41(t，3H).	418.10	458			376.00

460	4- [3- (4-Ethyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-2-methyl-pyridine	8.82(d，2H)，8.75(d，1H)，7.84(s，1H)，7.76(d，1H)，7.60(d，2H)，4.74(s，2H)，4.13(m，2H)，1.41(t，3H).
460			461	3- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -benzonitrile	8.11(s, 1H), 7.97(m, 3H), 7.83(d, 1H), 7.63(m, 3H), 7.50(t, 1H), 4.63(s, 2H) and 3.68(s, 3H)
462	5- (3-chloro-phenyl) -3- [5- (3-chloro-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.11(s, 1H), 8.00(d, 1H), 7.67(m, 1H), 7.50(m, 5H), 4.61(s, 2H) and 3.66(s, 3H).	461
462			463	5- (3-chloro-phenyl) -3- [5- (4-chloro-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.11(s, 1H), 8.01(d, 1H), 7.55(m, 6H), 4.61(s, 2H) and 3.64(s, 3H).
464	4- {5- [5- (2, 5-dichloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.80(dd，2H)，8.05(m，1H)，7.59(m，2H)，7.47(s，2H)，4.73(s，2H)，4.11(m，2H)，1.32 (m，3H).	463
464			465	5- (2, 5-dichloro-phenyl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4 ]Oxadiazoles as herbicides	8.06(dd，1H)，7.50(m，4H)，7.19(dd，1H)，4.68(s，2H)，4.17(q，2H)，1.39(t，3H).

466	5- (2, 5-difluoro-phenyl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.80(dd，2H)，7.79(m，1H)，7.60(m，2H)，7.28(m，1H)，4.68(s，2H)，4.11(q，2H)，1.39(t，3H).	406.10
466			406.10	467	4- {5- [5- (2, 5-difluoro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	7.80(m，1H)，7.52(m，1H)，7.48(m，1H)，7.20(m，4H)，4.68(s，2H)，4.17(m，2H)，1.40(t，3H).
468	5- (2, 5-dichloro-phenyl) -3- (4-ethyl-5-thiophen-3-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.07(dd，1H)，7.71(dd，1H)，7.49(m，4H)，4.69(s，2H)，4.12(m，2H)，1.38(t，3H).		467
468				469	5- (2, 5-difluoro-phenyl) -3- (4-ethyl-5-thiophen-3-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	7.80(m，1H)，7.72(m，1H)，7.49(m，2H)，7.28(m，2H)，4.68(s，2H)，4.12(q，2H)，1.37(t，3H).	406.10
470	4- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-propyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.80(dd，2H)，8.11(m，1H)，7.99(m，1H)，7.57(m，3H)，7.48(t，1H)，4.70(s，2H)，3.39(q，2H)，1.72(m，2H)，0.91(t，3H).		469			406.10
470				471	4- {5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-propyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.80(dd，2H)，7.87(dd，1H)，7.58(m，2H)，7.39(m，1H)，7.15(q，1H)，4.70(s，2H)，4.01(m，2H)，2.40(s，3H)，1.70(m，2H)，0.87(t，3H).

472	3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-thiophen-2-yl- [1, 2, 4]Oxadiazoles as herbicides	7.91(d, 1H), 7.67(d, 1H), 7.52(d, 1H), 7.48(d, 1H), 7.20(m, 2H), 4.62(s, 2H), 4.18(m, 2, all, 1.38(t, 3H).	376.10
472			376.10	473	3- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-thiophen-2-yl- [1, 2, 4]Oxadiazoles as herbicides	7.90(s, 1H), 7.74(d, 1H), 7.67(d, 1H), 7.52(m, 2H), 7.21(m, 1H), 4.60(s, 2 homo, 3.71(s, 3H)2.68(s, 3H).
474	4- [ 4-methyl-5- (3-thiophen-3-yl- [1, 2, 4 ]]Oxadiazol-5-ylmethylsulfanyl) -4H- [1, 2, 4]Triazol-3-yl]-pyridine	8.82(d, 2H), 8.05(s, 1H), 7.61(m, 3, 7.44(m, 1H), 4.73(s, 2H), 3.70(s, 3H).		473
474				475	5- (4-methyl-5-thiophen-3-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -3-thiophen-3-yl- [1, 2, 4]Oxadiazoles as herbicides	8.05(s，1H)，7.73(d，1H)，7.62(d，1H)，7.51(s，2H)，7.44(m，1H)，4.66(s，2H)，3.68(s，3H).
476	5- (4-Ethyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) -3-thiophen-3-yl- [1, 2, 4]Oxadiazoles as herbicides	8.05(d，1H)，7.62(d，1H)，7.53(d，2H)，7.47(d，1H)，7.44(m，1H)，7.19(m，1H，4.75(s，2H)，4.15(m，2H)，1.40(t，3H).	376.10	475
476			376.10	477	5- [3- (4-Ethyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-thiophene-3-carbonitrile	8.18(d，1H)，8.03(d，1H)，7.51(m，1H)，7.46(m，1H)，7.18(m，1H)，4.63(s，2H)，4.16(q，2H)，1.40(，3H).	401.00

478	5- (3-chloro-phenyl) -3- [5- (2-fluoro-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.13(s, 1H), 8.01(d, 1H), 7.52(m, 4H), 7.34(t, 1H), 7.27(m, 1H), 4.63(s, 2H) and 3.54(s, 3H).
478				479	5- (3-chloro-phenyl) -3- [5- (3-fluoro-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.11(s, 1H), 8.00(d, 1H), 7.52(m, 5H), 7.27(m, 1H), 4.62(s, 2H) and 3.66(s, 3H).	403.00
480	5- (3-chloro-phenyl) -3- [5- (4-fluoro-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.11(s, 1H), 8.00(d, 1H), 7.59(m, 4H), 7.49(t, 1H), 7.22(m, H), 4.61(s, 2H) and 3.64(s, 3H).	403.10	479			403.00
480			403.10	481	3- (5-benzo [ b ]]Thien-2-yl-4-methyl-4H- [1, 2, 4]Triazol-3-ylsulfanylmethyl) -5- (3-chloro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	8.11(s, 1H), 8.01(d, 1H), 7.87(m, 2H), 7.72(s, 1H), 7.58(d, 1H), 7.45(m, 3H), 4.60(s, 2H) and 3.85(s, 3H).
482	5-(3-chloro-phenyl) -3- [5- (3-methoxy-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.12(s, 1H), 8.01(d, 1H), 7.59(dd, 1H), 7.49(t, 1H), 7.44(t, 1H), 7.2(m, 2H), 7.05(dd, 1H), 4.60(s, 2H), 3.88(s, 3H) and 3.65(s, 3H).		481
482				483	5- (3-chloro-phenyl) -3- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.12(s, 1H), 8.01(d, 1H), 7.59(m, 3H), 7.49(t, 1H), 7.03(d, 2H), 4.59(s, 2H), 3.89(s, 3H) and 3.63(s, 3H).	415.00

484	3- (4-Ethyl-5-furan-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	7.86(dd，1H)，7.59(m，1H)，7.37(m，1H)，7.14(m，2H)，6.58(q，1H)，4.63(s，2H)，4.26(q，2H)，2.39(s，3H)，1.37(t，3H).	386.10
484			386.10	485	3- (4-Ethyl-5-furan-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 2, 4]Oxadiazoles as herbicides	7.91(m，2H)，7.59(m，1H)，7.40(m，2H)，7.10(q，1H)，6.58(q，1H)，4.61(s，2H)，4.24(q，2H)，2.43(s，3H)，1.36(t，3H).	368.20
486	3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	7.97(m，1H)，7.47(m，1 H)，7.16(t，1H)，4.72(d， 2H)，4.16(m，2H)，2.41(d，3H)，1.37(m，3H).		485			368.20
486				487	3- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-5-pyridin-4-yl- [1, 2, 4]Triazol-4-ylamines	(CD3OD as solvent): 8.72(m, 2H), 8.17(m, 2H), 7.86(dd, 1H), 7.49(m, 1H), 7.23(dd, 1H), 4.59(s, 2H), 2.35(s, 3H).
488	3- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-5-thiophen-2-yl- [1, 2, 4]Triazol-4-ylamines	(CD3OD as solvent): 8.05(s, 1H), 7.84(dd, 1H), 7.69(m, 1H), 7.47(m, 1H), 7.22(m, 2H), 4.52(s, 2H), 2.33(s, 3H).		487

489	3-pyridin-4-yl-5- (5-m-tolyl- [1, 2, 4)]Oxadiazol-3-ylmethylthio) - [1, 2, 4]Triazol-4-ylamines	(CD3OD as solvent): 8.73(dd, 2H), 8.17(dd, 2H), 7.89(m, 2H), 7.46(m, 2H), 4.58(s, 2H), 2.389(s, 3H).
489				490	3-thiophen-2-yl-5- (5-m-tolyl- [1, 2, 4)]Oxadiazoles as herbicides-3-ylmethylthio) - [1, 2, 4]Triazol-4-ylamines	(CD3OD as solvent): 8.05(dd, 1H), 7.87(d, 2H), 7.70(dd, 1H), 7.45(m, 2H)7.23(q, 1H), 4.50(s, 2H), 2.39(s, 3H).
491	3- (4-Ethyl-5-furan-2-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -5-thiophen-3-yl- [1, 2, 4]Oxadiazoles as herbicides	8.23(m，1H)，7.66(m，1H)，7.60(m，1H)，7.47(m，1H)，7.11(m，1H)，6.60(m，1H)，4.61(s，2H)，4.26(q，2H)，1.38(t，3H).	360.10	490
491			360.10	492	5- (3-chloro-phenyl) -3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4 ]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.11(m，1H)，8.00(m，1H)，7.59(m，2H)，7.51(t，1H)，7.12(m，1H)，6.60(m，1H)，4.63(s，2H)，4.26(q，2H)，1.38(t，3H).	389.00
493	4- [3- (4-Ethyl-5-furan-2-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-2-methyl-pyridine	8.73(d，1H)，7.82(s，1H)，7.75 (m，1H)，7.60(m，1H)，7.12(m，1H)，6.60(m，1H)，4.65(s，2H)，4.26(q，2H)，2.68(s，3H)，1.39(t，3H).		492			389.00

494	5- (2, 5-difluoro-phenyl) -3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	7.80(m，1H)，7.61(m，1H)，7.29(m，2H)，7.12(m，1H)，6.60(m，1H)，4.65(s，2H)，4.28(q，2H)，1.39(t，3H).	390.09
494			390.09	495	4- [ 4-Ethyl-5- (5-thiophen-3-yl-isoxazol-3-ylmethylsulfanyl) -4H- [1, 2, 4]Triazol-3-yl]-pyridine	8.81(m，2H)，7.63 (m，1H)，7.59(m，2H)，7.41(m，2H)，6.58(s，1H)，4.63(s，2H)，4.06(q，2H)，1.38(t，3H).	371.00
496	4-Ethyl-3-furan-2-yl-5- (5-thiophen-3-yl-isoxazol-3-ylmethylsulfanyl) -4H- [1, 2, 4]Triazole compounds	7.77(m，1H)，7.60(m，1H)7.40(m，2H)，7.10(m，1H)，6.60(m，1H)，6.55(s，1H)，4.58(s，2H)，4.21(q，2H)，1.38(t，3H).	359.10	495			371.00
496			359.10	497	5- (3-chloro-phenyl) -3- [5- (3, 5-dichloro-phenyl) -4-ethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.12(s, 1H), 8.01(d, 1H), 7.60(d, 1H), 7.54(s, 3H), 7.47(t, 1H), 4.69(s, 2H), 4.06(q, 2H) and 1.36(t, 3H).
498	5- (3-chloro-phenyl) -3- (4-ethyl-5-p-tolyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.13(s, 1H), 8.01(d, 1H), 7.53(m, 4H), 7.20(d, 2H), 4.68(s, 2H), 4.03(q, 3H), 2.45(s, 1H) and 1.32(t, 3H).		497
498				499	5- (3-chloro-phenyl) -3- (4-ethyl-5-m-tolueneradical-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.11(s, 1H), 8.00(d, 1H), 7.58(d, 1H), 7.29-7.50(m, 5H), 4.66(s, 2H), 4.02(q, 2H), 2.45(s, 1H) and 1.32(t, 3H).

500	5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (3-nitro-phenyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.52(s, 1H), 8.40(d, 1H), 8.12(s, 1H), 8.05(dd, 2H), 7.76(t, 1H), 7.60(d, 1H), 7.50(t, 1H), 4.72(s, 2H), 4.10(q, 2H) and 1.41(t, 3H).
500			501	4- {5- [3- (3-chloro-phenyl) -isoxazol-5-ylmethylsulfanyl]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	7.80(m，2H)，7.78(m，1H)，7.65(m，1H)，7.59(m，2H)，7.40(m，2H)，6.65(s，1H)，4.67(s，2H)，3.64(s，3H).
502	5- (3-chloro-phenyl) -3- [5- (2, 5-difluoro-phenyl) -4-ethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.14(s, 1H), 8.02(d, 1H), 7.60(d, 1H), 7.52(t, 1H), 7.32(m, 1H), 7.23(m, 2H), 4.70(s, 2H), 3.96(q, 2H) and 1.27(t, 3H).	501
502			503	5- (3-chloro-phenyl) -3- [5- (3-chloro-phenyl) -4-ethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.11(s, 1H), 8.06(d, 1H), 7.63(s, 1H), 7.58(d, 1H), 7.49(m, 4H), 7.23(m, 2H), 4.68(s, 2H), 4.04(q, 2) and 1.34(t, 3H).
504	5- (3-chloro-phenyl) -3- [5- (4-chloro-phenyl) -4-ethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.13(s, 1H), 8.01(d, 1H), 7.3(m, 6H), 4.68(s, 2H), 4.03(q, 2H) and 1.34(t, 3H).	503

505	4- {5- [5- (3-chloro-phenyl) -oxazol-2-ylmethylsulfanyl ]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.78(d, 2H), 7.55(m, 3H), 7.44(m, 1H), 7.29(m, 3H), 4.69(s, 2H), 4.04(q, 2H) and 1.34(t, 3H).
505				506	3- [5- (3-chloro-phenyl) -oxazol-2-ylmethylthio]-4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole compounds	7.55(s, 1H), 7.50(d, 1H), 7.44(m, 2H), 7.28(m, 3H), 7.18(dd, 1H), 4.64(s, 2H), 4.10(q, 2H) and 1.35(t, 3H).	404.00
507	3- [5- (3-chloro-phenyl) -oxazol-2-ylmethylthio]-4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazole compounds	7.58(s，1H)，7.53(s，1H)，7.40(m，1H) 7.27(m，3H)，7.10(d, 1H), 6.68(d, 1H), 4.62(s, 2H), 4.19(q, 2H) and 1.33(t, 3H).	388.00	506			404.00
507			388.00	508	5- (2-chloro-5-methyl-phenyl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	7.83(s，1H)，7.53(d，1H)，7.44(m，2H)，7.32(d，1H)，7.18(t，2H)4.63(s，2H)，4.17(q，2H)，2.37(s，3H)，1.38(t，3H).
509	4- {5- [3- (3-chloro-phenyl) -isoxazol-5-ylmethylsulfanyl]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.80(m，2H)，7.78(m，1H)，7.66(m，1H)，7.57(m，2H)，7.41(m，2H)，6.67(s，1H)，4.71(s，2H)，4.03(q，2H)，1.36(t，3H).		508

510	3- [3- (3-chloro-phenyl) -isoxazol-5-ylmethylsulfanyl]-4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole compounds	7.78(s，1H)，7.64(m，1H)7.52(m，1H)，7.41(m，3H)，7.18 (m，1H)，6.65(s，1H)，4.66(s，2H)，4.08(q，2H)，1.36(t，3H).	404.00
510			404.00	511	3- [3- (3-chloro-phenyl) -isoxazol-5-ylmethylsulfanyl]-4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazole compounds	7.77(s，1H)，7.64(d，1H)，7.59(m，1H)，7.39(m，2H)，7.10(m，1H)，6.62(s，1H)，6.59(m，1H)，4.65(s，2H)，4.17(q，2H)，1.35(t，3H).	388.10
512	4- {5- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines			511			388.10
512				513	5- (2, 5-dichloro-thiophen-3-yl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	(DMSO-D6 as solvent): 7.82(dd, 1H), 7.65(d, 1H), 7.58(m, 1H), 7.25(m, 1H), 4.60(s, 2H), 4.16(q, 2H), 1.24(t, 3H).
514	4- {5- [5- (2, 5-dichloro-thiophen-3-yl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.78(d，2H)，7.71(d，2H)，7.68(m，1H)，4.67(s，2H)，4.10(q，2H)，1.21(t，3H).		513

515	4- { 4-Ethyl-5- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-ylmethylsulfanyl]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.81(m，2H)，7.73(m，1H)，7.60(m，2H)，7.21(m，1H)，7.07(m，1H)，6.76(m，1H)，4.63(s，2H)，4.02(q，2H)，2.40(s，3H)，1.38(t，3H).
515			516	4-Ethyl-3- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-ylmethylsulfanyl]-5-thiophen-2-yl-4H- [1, 2, 4]Triazole compounds	7.71(d，1H)，7.53(m，1H)，7.47(m，1H)，7.46(m，2H)，7.07(m，1H)，6.77(d，1H)，4.63(s，2H)，4.12(q，2H)，2.40(s，3H)，1.39(t，3H).
517	4-Ethyl-3- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-ylmethylsulfanyl]-5-furan-2-yl-4H- [1, 2, 4]Triazole compounds	7.72(d，1)，7.60(m，1H)，7.10(m，1H)，7.05(m，2H)，6.77(d，1H)，6.60(m，1H)，4.61(s，2H)，4.21(q，2H)，2.39(s，3H)，1.38(t，3H).	516
517			518	5- (3-chloro-phenyl) -3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.11(s, 1H), 8.01(d, 1H), 7.60(d, 1H), 7.50(t, 1H), 4.72(s, 2H), 4.12(q, 2H) and 1.42(t, 3H).	391.00
519	3- (3-chloro-Phenyl) -5- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.05(s, 1H), 7.94(d, 1H), 7.50(d, 1H), 7.43(t, 1H), 4.83(s, 2H), 4.13(q, 2H) and 1.44(t, 3H).	518			391.00
519			520	3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -5-thiophen-3-yl- [1, 2, 4]Oxadiazoles as herbicides	8.23(s, 1H), 7, 65(d, 1H), 7.48(m, 1H), 4.69(s, 2H), 4.12(q, 2H) and 1.41(t, 3H).

521	5- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -3-thiophen-3-yl- [1, 2, 4]Oxadiazoles as herbicides	8.05(s, 1H), 7, 61(d, 1H), 7.43 (m, 1H), 4.81(s, 2H), 4.12(q, 2H) and 1.43(t, 3H).
521			522	5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (3-fluoro-phenyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.12(d，1H)，8.00(d，1H)，7.52(m，4H)，7.25(m，2H)，4.67(s，2H)，4.06(q，2H)，1.31(t，3H).
523	5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (4-fluoro-phenyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.10(s，1H)，7.99(d，1H)，7.59(m，4H)，7.48(t，1H)，7.22(d，1H)，4.67(s，2H)，4.01(q，2H)，1.30(t，3H).	522
523			524	3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5-thiophen-2-yl- [1, 2, 4]Oxadiazoles as herbicides	7.91(s, 1H), 7, 68(d, 1H), 7.21(m, 1H), 4.67(s, 2H), 4.13(q, 2H) and 1.41(t, 3H).
525	3{3- [5- (3-chloro-thiophen-2-yl) -4-ethyl-4H- [1, 2, 4 [ ]]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazol-5-yl } -benzonitrile	8.35(m，2H)，7.89(d，1H)，7.87(t，1H)，7.58(d，1H)，7.09(d，1H)，4.70(s，2H)，4.00(q，2H)，1.27(t，3H).	524
525			526	4- {5- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.82(d，2H)，8.01(d，1H)，9.93(m，1H)，7.59(m，2H)，7.52(m，1H)，7.47(m，1H)，4.83(s，2H)，4.11(q，2H)，1.40(t，3H).	400.10

527	2- (3-chloro-phenyl) -5- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4 ]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazoles as herbicides	8.00(s，1H)，7.89(d，1H)，7.60(m，1H)，7.50(m，1H)，7.44(m，1H)，7.13(m，1H)，6.60(m，1H)，4.76(s，2H)，4.25(q，2H)，1.38(t，3H).	389.00
527			389.00	528	5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.12(s，1H)，8.01(d，1H)，7.57(m，3H)，7.51(t，1H)，7.05(d，2H)，4.67(s，2H)，4.02(q，2H)，3.89(s，3H)，1.31(t，3H).
529	5- (3-chloro-phenyl) -3- [5- (2-fluoro-5-methyl-phenyl) -4-furan-2-ylmethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.12(s，1H)，8.02(d，1H)，7.58(d，1H)，7.52(d，1H)，7.35(d，2H)，7.23(s， 1H)，7.22(d，1H)，6.19(s，1H)，6.04(s，1H)，5.13(s，2H)，4.61(s，2H)，2.37(s，3H).		528
529				530	4- [3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-2-methyl-pyridine	8.74(d, 1H), 7, 81(s, 1H), 7.74(d, 1H), 4.74(s, 2H), 4.12(q, 2H)2.69(s, 1H) and 1.42(t, 3H).
531	3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (3-methoxy-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	7.70(d, 1H), 7, 60(s, 1H), 7.44(t, 1H), 7.16(d, 1H), 4.70(s, 2H), 4.12(q, 2H), 3.90(s, 3H) and 1.41(t, 3H).		530

532	5- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -3- (3-methoxy-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	7.63(d, 1H), 7, 56(s, 1H), 7.39(t, 1H), 7.07(d, 1H), 4.82(s, 2H), 4.12(q, 2H) and 1.42(t, 3H).
532			533	5- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) -3-thiophen-2-yl [1, 2, 4 ]]Oxadiazoles as herbicides	7.77(s, 1H), 7, 52(d, 1H), 7.16(m, 1H), 4.79(s, 2H), 4.13(q, 2H) and 1.42(t, 3H).
534	5- (5-chloro-2-fluoro-phenyl) -3- (4-ethyl-5-trifluoromethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.07(dd, 1H), 7.56(m, 1H), 7.24(dd, 1H), 4.73(s, 2H), 4.13(q, 2H) and 1.42(t, 3H).	533
534			535	3- [3- ((4-ethyl-5-trifluoromethyl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl) -benzonitriles	8.40(s, 1H), 8.34(d, 1H), 7.91(d, 1H), 7.01(t, 1H), 4.73(s, 2H), 4.12(q, 2H) and 1.42(t, 3H).	381.10
536	3- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-ethyl-5-trifluoromethyl-4H- [1, 2, 4]Triazole compounds	7.75(s, 1H), 7.63(m, 1H), 7.40(m, 2H), 6.73(s, 1H), 4.65(s, 2H), 4.07(q, 2H) and 1.40(t, 3H).	535			381.10
536			537	3- [5- (3-chloro-phenyl) -oxazol-2-ylmethylthio]-4-ethyl-5-trifluoromethyl-4H- [1, 2, 4]Triazole compounds	7.58(s, 1H), 7.46(d, 1H), 7.32(d, 3H), 4.74(s, 2H), 4.09(q, 2H) and 1.39(t, 3H).
538	4-Ethyl-3- (5-thiophen-3-yl-isoxazol-3-ylmethylsulfanyl) -5-trifluoromethyl-4H- [1, 2, 4]Triazole compounds	7.78(s, 1H), 7.39(m, 1H), 6.53(d, 1H), 4.63(s, 2H), 4.07(q, 2H) and 1.39(t, 3H).	537

539	4- {3- [5- (3-fluoro-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazol-5-yl } -2-methyl-pyridine	8.73(d，1H)，7.83(s，1H)，7.76(d，1H)，7.47(m，3H)，7.27(s，1H)，4.65(s，2H)，3.67(s，3H)，2.69(s，3H).
539			540	4- {3- [5- (3-chloro-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazol-5-yl } -2-methyl-pyridine	8.74(d，1H)，7.82(s，1H)，7.67(d，1H)，7.56(d，1H)，7.51(m，1H)，7.48(m，1H)，7.46(s，1H)，4.65(s，2H)，3.67(s，3H)，2.69(s，3H).
541	4- {3- [5- (4-chloro-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazol-5-yl } -2-methyl-pyridine	8.73(d，1H)，7.82(s，1H)，7.75(d，1H)，7.63(d，2H)，7.51(d，2H)，4.65(s，2H)，3.65(s，3H)，2.69(s，3H).	540
541			542	4- {3- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazol-5-yl } -2-methyl-pyridine	8.73(d，1H)，7.83(s，1H)，7.45(d，1H)，7.61(d，2H)，7.04(d，2H)，4.62(s，2H)，3.89(s，3H)，3.64(s，3H)，2.69(s，3H).
543	4- [3- (4-ethyl-5-p-tolyl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-2-methyl-pyridine	8.74(d，1H)，7.85(s，1H)，7.77(d，1H)，7.51(d，2H)，7.32(d，2H)，4.70(s，2H)，4.03(q，2H)，2.70(s，3H)，2.45(s，3H)，1.31(t，3H).	542

544	3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (3-fluoro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	(DMSO-D6 as solvent): 7.93(m, 1H), 7.86(m, 2H), 7.80(m, 1H), 7.67(m, 2H), 7.25(m, 1H), 4.61(s, 2H), 4.16(q, 2H), 1.24(t, 3H).	388.10
544			388.10	545	4- { 4-Ethyl-5- [5- (3-fluoro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.78(bs，2H)，7.92(m，2H)，7.71(d，2H)，7.68(m，1H)，7.27(m，1H)，4.70(s，2H)，4.10(q，2H)，1.39(t，3H).	383.10
546	5- (3-chloro-phenyl) -3- [5- (3, 5-difluoro-phenyl) -4-ethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.11(s，1H)，8.01(d，1H)，7.58(d，1H)，7.50(t，1H)，7.21(m，2H)，7.00(t，1H)，4.68(s，2H)，4.07(q，2H)，1.35(t，3H).		545			383.10
546				547	5- (3-fluoro-phenyl) -3- [5- (2, 6-difluoro-phenyl) -4-ethyl-4H- [1, 2, 4 ]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.12(s，1H)，8.02(d，1H)，7.59(m，2H)，7.52(d，1H)，7.41(d，1H)，7.04(d，1H)，4.73(s，2H)，4.21(q，2H)，1.42(t，3H).
548	2- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazole compounds-3-Thiylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-4-methyl-phenol	9.89(s，1H)，7.70(s，1H)，7.56(d，1H)，7.54(d，1H)，7.30(m，1H)，7.18(m，1H)，6.98(d，1H)，4.66(s，2H)，4.12(q，2H)，2.34(s，3H)，1.37(t，3H).	399.90	547

549	3- {1- [5- (3-chloro-phenyl) -isoxazol-3-yl]-ethylsulfanyl } -4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazole compounds	7.73(bs，1H)，7.59(m，2H)，7.41(m，2H)，7.10(dd，1H)，6.59(m，2H)，5.05(q，1H)，4.13(q，2H)，1.91(d，3H)，1.27(t，3H).	401.10
549			401.10	550	4- (5- {1- [5- (3-chloro-phenyl) -isoxazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.8(dd，2H)，7.74(bs，1H)，7.63(m，1H)，7.57(dd，2H)，7.40(m，2H)，6.62(s，2H)，5.15(q，1H)，4.05(q，2H)，1.95(d，3H)，1.34(t，3H).
551	3- [5- (4-butoxy-phenyl) -4-ethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-5- (3-chloro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	8.12(s，1H)，8.01(d，1H)，7.58(d，1H)，7.52(d，2H)，7.49(d，1H)，7.01(d，2H)，4.69(s，2H)，4.02(q，4H)，1.82(m，2H)，1.51(q，2H)，1.32(t，3H)，1.01(t，3H).		550
551				552	3- (5-benzo [1, 3 ]]dioxol-5-yl-4-ethyl-4H- [1, 2, 4]Triazol-3-ylsulfanylmethyl) -5- (3-chloro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	8.12(s，1H)，8.00(d，1H)，7.58(d，1H)，7.51(d，1H)，7.09(d，2H)，6.96(s，1H)，6.08(s，2H)，4.67(s，2H)，4.02(q，2H)，1.31(t，3H).
553	3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (2-methyl-thiazol-4-yl) - [1, 2, 4]Oxadiazoles as herbicides	8.11(s，1H)，7.48(m，2H)，7.16(t，1H)，4.63(s，2H)，4.13(q，2H)，2.82(s，3H)，1.37(t，3H).	391.90	552

554	3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (4-fluoro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	(DMSO-D6 as solvent: 8.21(m, 2H), 7.51(m, 2H), 7.21(m, 3H), 4.63(s, 2H), 4.16(q, 2H), 1.38(t, 3H).
554				555	4-Ethyl-3- {1- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl]-ethylsulfanyl } -5-furan-2-yl-4H- [1, 2, 4 ]Triazole compounds	7.71(dd，1H)，7.59(dd，1H)，7.26(m，1H)，7.06(m，2H)，6.66(d，1H)，6.58(dd，1H)，5.06(q，1H)，4.13(q，2H)，2.39(s，3H)，1.91(d，3H)，1.28(t，3H).
556	4- (4-Ethyl-5- {1- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl]-ethylthio } -4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.79(dd，2H)，7.71(dd，1H)，7.59(dd，2H)，7.23(m，1H)，7.06(m，1H)，6.64(d，1H)，5.15(q，1H)，4.01(q，2H)，2.39(s，3H)，1.94(d，3H)，1.30(t，3H).	410.10	555
556			410.10	557	5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (3-methyl-3H-imidazol-4-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.11(s，1H)，8.00(d，1H)，7.66(s，1H)，7.58(d，1H)，7.52(t，1H)，7.37(s，1H)，4.69(s，2H)，4.09(q，2H)，3.93(s，3H)，1.37(t，3H).
558	5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (1-methyl-1H-imidazol-2-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.12(s，1H)，8.01(d，1H)，7.57(d，1H)，7.51(t，1H)，7.17(s，1H)，7.04(s，1H)，4.69(s，2H)，4.56(q，2H)，4.12(s，3H)，1.40(t，3H).		557

559	5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (1-methyl-1H-imidazol-4-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.12(s，1H)，8.01(d，1H)，7.65(s，1H)，7.57(d，1H)，7.48(d，2H)，4.60(s，2H)，4.50(q，2H)，3.79(s，3H)，1.36(t，3H).
559			560	4- {5- [5- (3-chloro-phenyl) -4-methyl-isoxazol-3-ylmethylsulfanyl]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.81(bs，2H)，7.70(m，1H)，7.61(m，3H)，7.44(m，2H)，4.65(s，2H)，4.09(q，2H)，2.31(s，3H)，1.40(t，3H).
561	3- [5- (3-chloro-phenyl) -4-methyl-isoxazol-3-ylmethylsulfanyl]-4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazole compounds	7.70(s，1H)，7.60(m，2H)，7.43(m，2H)，7.10(m，1H)，6.59(m，1H)，4.59(s，2H)，4.23(q，2H)，2.28(s，3H)，1.38(t，3H).	560
561			562	3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (4-methyl-thiophen-2-yl) - [1, 2, 4]Oxadiazoles as herbicides	7.61(d，1H)，7.49(m，2H)，7.22(m，2H)，4.59(s，2H)，4.16(q，2H)，2.32(s，3H)，1.38(t，3H).
563	5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (3-methyl-thiophen-2-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.13(s，1H)，8.01(d，1H)，7.58(d，1H)，7.52(d，1H)，7.45(d，1H)，7.02(d，1H)，4.69(s，2H)，3.97(q，2H)，2.32(s，3H)，1.28(t，3H).	562

564	5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (5-methyl-thiophen-2-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.11(s，1H)，8.01(d，1H)，7.58(d，1H)，7.51(t，1H)，7.28(s，1H)，6.83(d，1H)，4.64(s，2H)，4.14(q，2H)，2.56(s，3H)，1.39(t，3H).
564			565	4- {5- [ 4-chloro-5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl ]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.81(d，2H)，7.99(m，1H)，7.90(m，1H)，7.60(m，2H)，7.48(m，2H)，4.65(s，2H)，4.10(q，2H)，1.39(t，3H).
566	3- [ 4-chloro-5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazole compounds	7.99(s，1H)，7.90(m，1H)，7.60(m，1H)，7.47(m，2H)，7.12(m，1H)，6.60(m，1H)，4.59(s，2H)，4.25(q，2H)，1.38(t，3H).	565
566			567	2-chloro-4- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl }-6-methyl-pyridine	8.11(s，1H)，8.00(d，1H)，7.58(d，1H)，7.52(d，1H)，7.40(d，2H)，4.71(s，2H)，4.10(q，2H)，2.64(s，3H)，1.40(t，3H).
568	3- [5- (5-bromo-furan-2-yl) -4-ethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-5- (3-chloro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	8.11(s，1H)，7.99(d，1H)，7.58(d，1H)，7.51(t，1H)，7.07(d，1H)，6.52(d，1H)，4.64(s，2H)，4.23(q，2H)，1.40(t，3H).	567

569	2-chloro-4- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.59(d，1H)，8.10(s，1H)，8.00(d，1H)，7.66(s，1H)，7.59(d，1H)，7.54(d，1H)，7.50(d，1H)，4.72(s，2H)，4.11(q，2H)，1.42(t，3H).
569				570	2-chloro-4- {5- [5- (3-chloro-phenyl) - [ 12, 4 ]]Oxadiazol-3-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -6-methoxy-pyridine	8.11(s，1H)，8.00(d，1H)，7.58(d，1H)，7.50(t，1H)，7.24(s，1H)，6.91(s，1H)，4.70(s，2H)，4.08(q，2H)，4.02(s，3H)，1.39(t，3H).	464.10
571	2- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-4-methyl-benzonitrile	8.02(s，1H)，7.76(d，H)，7.47(m，3H)，7.17(t，1H)，4.68(s，2H)，4.19(q，2H)，2.51(s，3H)，1.39(t，3H).		570			464.10
571				572	5- (3-chloro-phenyl) -3- [ 4-ethyl-5- (3-methoxy-thiophen-2-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	8.14(s，1H)，8.03(d，1H)，7.58(d，1H)，7.50(d，1H)，7.44(d，1H)，6.94(1H)，4.67(s，2H)，4.03(q，2H)，3.88(s，3H)，1.29(t，3H).
573	3- [5- (5-chloro-thiophen-3-yl) -isoxazol-3-ylmethylsulfanyl]4-Ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazole compounds	7.61(m，1H)，7.52(d，1H)，7.21(d，1H)，7.11(m，1H)，7.61(m，1H)，6.55(s，1H)，4.57(s，2H)，4.21(q，2H)，1.38(t，3H).	393.10	572

574	3- [3- (4-Ethyl-5-furan-2-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl ]-5-fluoro-benzonitrile	8.21(m，1H)，8.04(dd，1H)，7.59(m，2H)，7.10(dd，1H)，6.59(dd，1H)，4.64(s，2H)，4.25(q，2H)，1.38(t，3H).
574			575	4-Ethyl-3- (5-phenyl-isoxazol-3-ylmethylsulfanyl)) -5-thiophen-2-yl-4H- [1, 2, 4]Triazole compounds	7.77(m, 2H), 7.53(d, 1H), 7.47(m, 4H), 7.19(dd, 1H), 6.71(s, 1H), 4.61(s, 2H), 4.12(q, 2H) and 1.39(t, 3H).
576	4-methyl-3- (5-phenyl-isoxazol-3-ylmethylsulfanyl) -5-thiophen-3-yl-4H- [1, 2, 4]Triazole compounds	7.77(m, 3H), 7.50(m, 5H), 6.69(s, 1H), 4.56(s, 2H) and 3.67(s, 3H)	575
576			577	4-Ethyl-3-furan-2-yl-5- (5-phenyl-isoxazol-3-ylmethylsulfanyl) -4H- [1, 2, 4]Triazole compounds	7.77(m, 2H), 7.61(s, 1H), 7.46(m, 3H), 7.14(d, 1H), 6.69(s, 1H), 6.60(d, 1H), 4.60(s, 2H), 4.22(q, 2H) and 1.38(t, 3H).
578	4- [ 4-Ethyl-5- (5-phenyl-isoxazol-3-ylmethylsulfanyl) -4H- [1, 2, 4]Triazol-3-yl]-pyridine	8.82(w, 2H), 7.77(m, 2H), 7.61(d, 2H), 7.45(m, 3H), 6.71(s, 1H), 4.65(s, 2H), 4.06(q, 2H) and 1.39(t, 3H).	577
578			579	4- [ 4-methyl-5- (5-phenyl-isoxazol-3-ylmethylsulfanyl) -4H- [1, 2, 4]Triazol-3-yl]-pyridine	8.81(w, 2H), 7.77(m, 2H), 7.63(d, 2H), 7.46(m, 3H), 6.70(s, 1H), 4.60(s, 2H) and 3.68(s, 3H).

580	2- (4-Ethyl-5-furan-2-yl-4H- [1, 2, 4) ]Triazol-3-ylsulfanylmethyl) -5-m-tolyl- [1, 3, 4]Oxadiazoles as herbicides	7.80(m，2H)，7.70(m，1H)，7.35(m，2H)，7.13(m，2H)，6.60(m，1H)，4.74(s，2H)，4.23(q，2H)，2.40(s，3H)，1.36(t，3H).	368.10
580			368.10	581	4- [ 4-methyl-5- (5-m-tolyl- [1, 3, 4 ]]Oxadiazol-2-ylmethylsulfanyl) -4H-[1，2，4]Triazol-3-yl]-pyridine	8.81(m，2H)，7.80(m，2H)，7.61(d，2H)，7.39(m，2H)，4.74(s，2H)，3.71(s，3H)，2.4(s，3H).	365.10
582	4- [ 4-Ethyl-5- (5-m-tolyl- [1, 3, 4 ]]Oxadiazol-2-ylmethylsulfanyl) -4H- [1, 2, 4]Triazol-3-yl]-pyridine	8.81(d，2H)，7.81(m，2H)，7.58(m，2H)，7.37(m，2H)，4.81(s，2H)，4.41(q，2H)，2.42(s，3H)，1.33(t，3H).	379.10	581			365.10
582			379.10	583	4- {5- [5- (5-chloro-thiophen-3-yl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.80(d，2H)，7.98(m，1H)，7.58(d，2H)，7.46(d，1H)，4.66(s，2H)，4.10(q，2H)，1.38(t，3H).	405.90
584	3- [3- (4-Ethyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-4-fluoro-benzonitrile	8.79(bs，2H)，8.46(m，1H)，7.91(m，1H)，7.59(d，2H)，7.43(t，1H)，4.74(s，2H)，4.12(q，2H)，1.41(t，3H).		583			405.90

585	3- [3- (4-Ethyl-5-furan-2-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-4-fluoro-benzonitrile	8.45(dd，1H)，7.91(m，1H)，7.59(d，1H)，7.43(t，1H)，7.10(d，1H)，6.58(dd，1H)，4.65(s，2H)，4.27(q，2H)，1.39(t，3H).	397.10
585			397.10	586	3- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-4-fluoro-benzonitrile	8.45(dd，1H)，7.90(m，1H0，7.47(m，3H)，7.18(t，1H)，4.68(s，2H)，4.17(q，2H)，1.41(t，3H).
587	3- [3- (4-Ethyl-5-furan-2-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-benzonitrile	8.41(m，2H)，7.89(d，1H)，7.69(d，1H)，7.13(m，1H)，6.60(m，1H)，4.65(s，2H)，4.27(q，2H)，1.40(t，3H).	379.10	586
587			379.10	588	3- [5- (4-Ethyl-5-furan-2-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-3-yl]-benzonitrile	8.36(m，2H)，7.80(t，1H)，7.62(m，2H)，7.15(m，1H)，6.61(m，1H)，4.78(s，2H)，4.2(q，2H)，1.40(t，3H).	379.10
589	3- [3- (4-methyl-5-trifluoromethyl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-benzonitrile	8.41(m，2H)，7.90(m，1H)，7.72(t，1H)，4.68(s，2H)，3.73(s，3H).		588			379.10
589		8.41(m，2H)，7.90(m，1H)，7.72(t，1H)，4.68(s，2H)，3.73(s，3H).		590	5- (5-chloro-2-fluoro-phenyl) -3- (4-methyl-5-trifluoromethyl-4H- [1, 2, 4 ]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.08(m，1H)，7.58(m，1H)，7.25(m，1H)，4.67(s，2H)，3.74(s，3H).	394.90

591	2-chloro-4- [3- (4-ethyl-5-furan-2-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-pyridine	8.63(m，1H)，8.02(m，1H)，7.89(m，1H)，7.61(m，1H)，7.14(m，1H)，6.61(m，1H)，4.67(s，2H)，4.27(q，2H)，1.40(t，3H).	390.00
591			390.00	592	2-chloro-4- [3- (5-furan-2-yl-4-methyl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-pyridine	8.63(d，1H)，8.00(d，1H)，7.88(m，1H)，7.62(d，1H)，7.14(d，1H)，6.61(m，1H)，4.60(s，2H)，3.82(s，3H).
593	2- (3-chloro-phenyl) -5- [ 4-methyl-5- (2-methyl-thiazol-4-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，3，4]Oxadiazoles as herbicides	7.98(m，2H)，7.89(d，1H)，7.49(m，1H)，7.44(m，1H)，4.69(s，2H)，3.92(s，3H)，2.77(s，3H).		592
593				594	2- (3-chloro-phenyl) -5- (4-methyl-5-thiazol-4-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazoles as herbicides	8.91(s，1H)，8.24(s，1H)，7.98(s，1H)，7.91(d，1H)，7.49(m，1H)，7.43(m，1H)，4.72(s，2H)，3.96(s，3H).
595	2- (3-chloro-phenyl) -5- (5-furan-2-yl-4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazoles as herbicides	8.00(s，1H)，7.89(d，1H)，7.60(s，1H)，7.53(m，1H)，7.43(m，1H)，7.12(d，1H)，6.60(dofd，1H)，4.68(s，2H)，3.80(s，3H).		594
595				596	2- (3-chloro-phenyl) -5- (4-ethyl)-5-trifluoromethyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazoles as herbicides	8.00(s，1H)，7.90(d，1H)，7.52(m，2H)，4.86(s，2H)，4.13(q， 2H)，1.42(t，3H).

597	4- (4-Ethyl-5- [5- (4-methyl-thiophen-2-yl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.79(d，2H)，7.68(s，1H)，7.59(d，2H)，7.23(m，1H)，4.63(s，2H)，4.10(q，2H)，2.32(d，3H)，1.37(t，3H).
597			598	3- (4-Ethyl-5-furan-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (4-methyl-thiophen-2-yl) - [1, 2, 4]Oxadiazoles as herbicides	7.67(d，1H)，7.59(m，1H)，7.2(s，1H)，7.09(d，1H)，6.58(dd，1H)，4.56(s，2H)，4.24(q，2H)，2.32(s，3H)，1.36(t，3H).	374.00
599	3- (3-chloro-phenyl) -5- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.02(m，1H)，7.91(m，1H)，7.57(d，1H)，7.35(m，2H)，7.08(d，1H)，6.56(dd，1H)，4.72(s，2H)，4.22(q，2H)，2.32(s，3H)，1.36(t，3H).	598			374.00
599			600	4- {5- [3- (3-chloro-phenyl) - [1, 2, 4 ] ]Oxadiazol-5-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.79(dd，2H)，8.02(m，1H)，7.92(m，1H)，7.57(dd，2H)，7.42(m，2H)，4.80(s，2H)，4.08(q，2H)，1.38(t，3H).
601	4- { 4-Ethyl-5- [5- (3-Nitro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-ylmethylthio]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.87(m，3H)，8.42(m，2H)，7.75(t，1H)，7.66(d，2H)，4.88(s，2H)，4.15(q，2H)，1.45(t，3H).	600

602	2- (4-Ethyl-5-furan-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (3-nitro-phenyl) - [1, 3, 4]Oxadiazoles as herbicides	8.87(t，1H)，8.39(m，2H)，7.73(t，1H)，7.61(m，1H)，7.15(m，1H)，6.61(m，1H)，4.28(q，2H)，1.78(s，2H)，1.41(t，3H).
602				603	4- {5- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.79(d，2H)，7.78(m，3H)，7.66(m，1H)，7.39(m，2H)，6.84(s，1H)，4.69(s，2H)，3.27(m，1H)，1.20(q，2H)，0.83(m，2H).	411.00
604	3- [5- (3-chloro-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4]Triazole compounds	7.77(m，1H)，7.65(m，1H)，7.56(m，2H)，7.41(m，2H)，7.04(m，2H)，6.79(s，1H)，4.61(s，2H)，3.97(q，2H)，3.89(s，3H)，1.32(t，3H).	428.20	603			411.00
604			428.20	605	5- (3-chloro-phenyl) -3- [1- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthio) -ethyl]-[1，2，4]Oxadiazoles as herbicides	8.08(m，1H)，7.96(dd，1H)，7.45(m，4H)，7.17(m，1H)，4.93(q，1H)，3.67(s，3H)，1.91(d，3H).	404.92
606	5- (3-chloro-phenyl) -3- [1- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthio) -ethyl]-[1，2，4]Oxadiazoles as herbicides	8.1(d，1H)，7.98(d，1H)，7.51(m，4H)，7.17(t，1H)，5.11(q，1H)，4.11(q，2H)，1.93(d，3H)，1.34(t，3H).	418.90	605			404.92

607	4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.79(dd，2H)，8.08(m，1H)，7.98(dd，1H)，7.59(m，3H)，7.46(t，1H)，5.05(q，1H)，3.66(s，3H)，1.94(d，3H).	400.07
607			400.07	608	4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.79(dd，2H)，8.10(m，1H)，7.99(dd，1H)，7.58(m，3H)，7.47(t，1H)，5.20(q，1H)，4.06(q，2H)，1.96(d，3H)，1.33(t，3H).	414.05
609	3- [5- (4-Ethyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazol-2-yl]-benzonitrile	8.84(s，2H)，8.30(m，2H)，7.85(m，1H)，7.66(m，3H)，4.84(s，2H)，4.14(q，2H)，1.43(t，3H).		608			414.05
609				610	3- [5- (4-Ethyl-5-furan-2-yl) -4H- [1, 2, 4 ]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazol-2-yl]-benzonitrile	8.27(m，2H)，7.82(m，1H)，7.62(m，2H)，7.18(t，1H)，6.62(m，1H)，4.79(s，2H)，4.27(q，2H)，1.40(t，3H).
611	3- [5- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazol-2-yl]-benzonitrile	8.83(d，2H)，8.31(m，2H)，7.84(m，4H)，4.81(s，2H)，3.77(s，3H).		610
611		8.83(d，2H)，8.31(m，2H)，7.84(m，4H)，4.81(s，2H)，3.77(s，3H).		612	3- [5- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazol-2-yl]-benzonitrile	8.82(s，2H)，8.33(m，2H)，7.86(t，3H)，7.67(t，1H)，4.91(d，2H)，1.24(m，3H)，0.88(m，2H).	402.20

613	4- {5- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	(CD3OD as solvent): 8.80(s (br), 2H), 7.96(m, 2H), 7.81(d, 2H), 7.61(m, 2H), 4.73(s, 2H), 3.84(s, 3H).
613				614	4- {5- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-ylmethylthio]-4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	(CD3OD as solvent): 8.75(d, 2H), 8.02(s, 1H), 7.96(d, 1H), 7.89(d, 2H), 7.60(m, 2H), 4.89(s, 2H), 3.59(m, 1H), 1.21(m, 2H), 0.84(m, 2H).	412.16
615	4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4%]Oxadiazol-2-ylmethylthio]-4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	7.80(m，2H)，8.04(m，1H)，7.77(d，2H)，7.51(m，1H)，7.21(t，1H)，4.92(s，2H)，3.32(m，1H)，1.21(m，2H)，0.85(m，2H).	430.11	614			412.16
615			430.11	616	2- (5-chloro-2-fluoro-phenyl) -5- [ 4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，3，4]Oxadiazoles as herbicides	8.02(m，1H)，7.52(m，3H)，7.20(t，1H)，7.04(m，2H)，4.81(s，2H)，4.03(q，2H)，3.89(s，3H)，1.33(t，3H).
617	4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4% ]Oxadiazol-2-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.83(d，2H)，8.03(m，1H)，7.65(m，2H)，7.51(m，1H)，7.20(t，1H)，4.78(s，2H)，3.75(s，3H).		616

618	4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4%]Oxadiazol-2-ylmethylthio]-4-ethyl-4H- [1，2，4]Triazol-3-yl } -pyridines	8.82(bs，2H)，8.02(m，1H)，7.61(m，2H)，7.51(m，1H)，7.20(t，1H)，4.85(s，2H)，4.13(q，2H)，1.41(t，3H).
618				619	2- (3-chloro-phenyl) -5- [ 4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，3，4]Oxadiazoles as herbicides	8.01(dd overlap, 1H), 7.85(d, 1H), 7.51(m, 4H), 7.00(d, 2H), 4.79(s, 2H), 4.00(q, 2H), 3.88(s, 3H), 1.30(t, 3H).
620	2- (3-chloro-phenyl) -5- [1- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazol-3-ylthio]-ethyl radical]-[1，3，4]Oxadiazoles as herbicides	7.97(s，1H)，7.84(d，1H)，7.58(d，1H)，7.49(m，1H)，7.40(m，1H)，7.12(d，1H)，6.59(d ofd，1H)，5.16(q，1H)，4.17(q，2H)，2.02(d，3H)，1.28(t，3H).		619
620				621	5- (5-chloro-2-fluoro-phenyl) -3- [1- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthio) -ethyl]-[1，2，4]Oxadiazoles as herbicides	8.06(m，1H)，7.54(m，3H)，7.23(m，2H)，4.93(q，1H)，3.72(s，3H)，1.91(d，3H).
622	4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-3-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.79(dd，2H)，8.07(dd，1H)，7.62(dd，2H)，7.54(m，1H)，7.21(t，1H)，5.07(q，1H)，3.69(s，3H)，1.95(d，3H).	418.10	621

623	4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.79(dd，2H)，8.08(m，1H)，7.57(m，3H)，7.22(t，1H)，5.21(q，1H)，4.08(q，2H)，1.97(d，3H)，1.35(t，3H).
623				624	2-chloro-4- [3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4-]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-pyridine	8.83(m，2H)，8.65(m，1H)，8.05(t，1H)，7.92(t，1H)，7.76(t，2H)，4.82(2H)，3.31(m，1H)，1.23(m，2H)，0.86(m，2H).
625	4- {5- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4 ]]Oxadiazol-2-ylmethylthio ]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.83(t，2H)，7.82(m，1H)，7.63(m，2H)，7.32(m，1H)，7.10(m，1H)，4.75(s，2H)，3.73(s，3H)，2.39(s，3H)，1.61(d，1H).		624
625				626	4- { 4-Ethyl-5- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4 ]]Oxadiazol-2-ylmethylthio]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.82(d，2H)，7.82(m，1H)，7.59(t，2H)，7.33(m，1H)，7.11(m，1H)，4.82(s，2H)，4.10(m，2H)，2.39(s，3H)，1.38(t，3H).	397.08
627	4- { 4-cyclopropyl-5- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4 ]]Oxadiazol-2-ylmethylthio]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.80(s，2H)，7.84(m，1H)，7.76(d，2H)，7.32(m，1H)，7.12(q，1H)，4.91(s，2H)，3.31(m，1H)，2.39(d，3H)，1.21(m，2H)，0.84(m，2H).	409.15	626			397.08

628	2- (4-Ethyl-5-furan-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4]Oxadiazoles as herbicides	7.77(m，1H)，7.61(m，1H)，7.32(d，1H)，7.12(m，2H)，6.61(m，1H)，4.76(s，2H)，4.26(q，2H)，2.37(d，3H)，1.23(t，3H).
628				629	2- [ 4-Ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4]Oxadiazoles as herbicides	7.81(m，1H)，7.54(m，2H)，7.32(d，1H)，7.11(m，1H)，7.03(m，2H)，4.79(s，2H)，4.02(q，2H)，3.89(s，3H)，2.37(d，3H)，1.31(t，3H).	426.15
630	4- {5- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-ethyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.82(dd，2H)，7.91(dd，1H)，7.60(dd，2H)，7.38(m，1H)，7.15(m，1H)，6.86(d，1H)，4.67(s，2H)，4.05(q，2H)，1.37(t，3H).	417.02	629			426.15
630			417.02	631	4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.81(dd，2H)，7.91(dd，1H)，7.59(dd，2H)，7.38(m，1H)，7.15 (m，1H)，6.74(d，1H)，5.20(q，1H)，4.05(q，2H)，1.95(d，3H)，1.34(t，3H).	431.10
632	4- {5- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.82(dd，2H)，7.91(dd，1H)，7.63(dd，2H)，7.39(m，1H)，7.15(m，1H)，6.85(d，1H)，4.62(s，2H)，3.69(s，3H).	403.10	631			431.10

633	4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.81(dd，2H)，7.91(dd，1H)，7.60(dd，2H)，7.38(m，1H)，7.15(m，1H)，6.72(d，1H)，5.06(q，1H)，3.64(s，3H)，1.93(d，3H).	417.10
633			417.10	634	4- {5- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.8(dd，2H)，7.92(dd，1H)，7.76(dd，2H)，7.38(m，1H)，7.15(m，1H)，6.95(d，1H)，4.71(s，2H)，3.27(m，1H)，1.18(m，2H)，0.82(m，2H).	429.10
635	4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl ]-ethylthio } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.78(dd，2H)，7.92(dd，1H)，7.76(dd，2H)，7.38(m，1H)，7.15(m，1H)，6.85(d，1H)，5.40(q，1H)，3.24(m，1H)，1.98(d，3H)，1.88(m，2H)，0.80(m，2H).	443.20	634			429.10
635			443.20	636	3- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-ylmethylsulfanyl]-4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazole compounds	7.90(dd，1H)，7.60(dd，1H)，7.39(m，1H)，7.11(m，2H)，6.85(d，1H)，6.59(dd，1H)，4.62(s，2H)，4.20(q，2H)，1.38(t，3H).
637	3- {1- [5- (5-chloro-2-fluoro-phenyl) -isoxazol-3-yl]-ethylsulfanyl } -4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazole compounds	7.88(dd，1H)，7.59(dd，1H)，7.39(m，1H)，7.11(m，2H)，6.74(d，1H)，6.58(dd，1H)，5.08(q，1H)，4.20(q，2H)，1.92(d，3H)，1.34(t，3H).		636

638	4- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	1.96(d，3H)3.61(s，3H)5.10(q，1H)7.38(t，1H)7.47 (m，1H)7.54(m，2H)7.84(m，1H)7.93(m，1H)8.74(d，2H)
638				639	4- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.80(bs，2H)，7.99(m，1H)，7.90(m，1H)，7.58(d，2H)，7.51(m，1H)，7.46(t，1H)，5.31(q，1H)，4.06(q，2H)，2.04(d，3H)，1.31(t，3H).	414.10
640	4- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-ethylthio } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.79(bs，2H)，8.03 (m，1H)，7.94(d，1H)，7.76(d，2H)，7.51(m，1H)，7.45(t，1H)，7.54(q，1H)，3.25(m，1H)，2.06(d，3H)，1.19(m，2H)，0.81(m，2H).	426.07	639			414.10
640			426.07	641	5- (5-chloro-2-fluoro-phenyl) -3- (5-furan-2-yl-4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.06(dd，1H)，7.60(d，1H)，7.55(m，1H)，7.22(t，1H)，7.09(d，1H)，6.58(m，1H)，4.55(s，2H)，3.81(s，3H).
642	5- (5-chloro-2-fluoro-phenyl) -3- (5-furan-3-yl-4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.06(dd，1H)，7.89(d，1H)，7.55(m，2H)，7.22(t，1H)，6.88(dd，1H)，4.55(s，2H)，3.67(s，3H).		641

643	4-chloro-2- [3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-phenol	10.08(s，1H)，7.88(d，1H)，7.47(m，3H)，7.17(t，1H)，7.06(d，1H)，4.68(s，2H)，4.14(q，2H)，1.38(t，3H).
643			644	2-chloro-4- [5- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 3, 4 ]Oxadiazol-2-yl]-pyridine	8.83(d，2H)，8.60(m，1H)，7.94(m，1H)，7.85(m，1H)，7.62(m，2H)，4.82(s，2H)，3.75(s，3H).
645	2-chloro-4- [5- (4-ethyl-5-pyridin-4-yl-4H- [1, 2, 4-]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazol-2-yl]-pyridine	8.82(d，2H)，8.60(m，1H)，7.94(m，1H)，7.86(m，1H)，7.59(m，2H)，4.87(s，2H)，4.12(q，2H)，1.43(t，3H).	644
645			646	2-chloro-4- [5-, (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazol-2-yl]-pyridine	8.81(d，2H)，8.60(m，1H)，7.96(m，1H)，7.86(m，1H)，7.75(m，2H)，4.92(s，2H)，3.32(m，1H)，1.21(m，2H)，0.87(q，2H).
647	2-chloro-4- [5- (4-ethyl-5-furan-2-yl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazol-2-yl]-pyridine	8.57(m，1H)，7.92(m，1H)，7.81(m，1H)，7.61(m，1H)，7.12(m，1H)，6.61(m，1H)，4.79(s，2H)，4.26(q，2H)，1.40(t，3H).	646
647			648	2-chloro-4- {5- [ 4-ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，3，4]Oxadiazol-2-yl } -pyridines	8.59(m，1H)，7.94(m，1H)，7.84(m，1H)，7.55(m，2H)，7.05(m，2H)，4.83(s，2H)，4.02(q，2H)，1.34(t，3H).

649	2- (3-chloro-phenyl) -5- {1- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthio]-ethyl } - [1, 3, 4]Oxadiazoles as herbicides	8.00(m，1H)，7.87(d，1H)，7.53(m，3H)，7.42(t，1H)，7.01(m，2H)，5.07(q，1H)，3.88(s，3H)，3.54(s，3H)，2.00(d，3H).
649				650	4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4%]Oxadiazol-2-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.81(bs，2H)，8.01(m，1H)，7.63(d，2H)，7.50(m，1H)，7.18(m，1H)，5.17(q，1H)，3.69(s，3H)，2.02(d，3H).
651	5- (5-bromo-2-fluoro-phenyl) -3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.20(m，1H)，7.65(m，1H)，7.60(s，1H)，7.13(m，2H)，6.56(m，1H)，4.64(s，2H)，4.25(q，2H)，1.38(t，3H).		650
651				652	2- (3-chloro-phenyl) -5- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，3，4]Oxadiazoles as herbicides	8.02(d，1H)，7.90(d，1H)，7.50(m，4H)，7.03(d，2H)，4.71(s，2H)，3.88(s，3H)，3.61(s，3H).
653	4- {5- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-ylmethylthio]-4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.79(d，2H)，8.09(t，1H)，7.97(m，1H)，7.76(d，2H)，7.45(m，2H)，4.89(s，2H)，3.30(m，1H)，1.22(m，2H)，0.86(m，2H).	412.07	652

654	4- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.78(s，2H)，8.14(m，1H)，8.04(m，1H)，7.77(t，2H)，7.54(m，2H)，4.79(s，2H)，3.29(m，1H)，1.21(m，2H)，0.85(d，2H).
654			655	4- (5- {1- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.79(s，2H)，7.79(t，1H)，7.61(t，2H)，7.33(m，1H)，7.08(m，1H)，5.09(m，1H)，3.65(s，3H)，2.37(s，3H)，2.02(d，3H).
656	4- (4-Ethyl-5- {1- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-ethylthio } -4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.81(m，2H)，8.23(m，1H)，7.79(d，2H)，7.32(m，1H)，7.09(m，1H)，5.28(m，1H)，4.07(m，2H)，2.37(s，3H)，2.04(d，3H)，1.24(m，3H).	655
656			657	4- (4-cyclopropyl-5- {1- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-ethylthio } -4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.78(m，2H)，7.82(d，1H)，7.74(d，2H)，7.31(m，1H)，7.11(m，1H)，5.51(m，1H)，3.23(m，1H)，2.38(s，3H)，2.06(d，3H)，1.16(m，2H)，0.78(m，2H).
658	4- (4-Cyclopropylmethyl-5- {1- [5- (2-fluoro-5-methyl-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-ethylthio } -4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.83(m，2H)，7.78(m，1H)，7.59(m，2H)，7.33(m，1H)，7.10(m，1H)，5.26(m，1H)，3.90(m，2H)，2.37(s，3H)，2.03(d，3H)，0.92(m，1H)，0.48(m，2H)，0.21(m，2H).	657

659	2- (2-fluoro-5-methyl-phenyl) -5- {1- [ 4-methyl-5- (2-methyl-thiazol-4-yl) -4H- [1, 2, 4-]Triazol-3-ylthio]-ethyl } - [1, 3, 4]Oxadiazoles as herbicides	7.98(s，1H)，7.75(m，1H)，7.31(m，1H)，7.08(m，1H)，5.03(q，1H)，3.85(s，3H)，2.75(s，3H)，2.35(s，3H)，1.98(d，3H).
659			660	4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4%]Oxadiazol-2-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.80(m，2H)，8.01(m，1H)，7.58(m，2H)，7.49(m，1H)，7.19(m，1H)，5.32(q，1H)，4.08(q，2H)，2.04(d，3H)，1.35(t，3H).
661	4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4%]Oxadiazol-2-yl]-ethylthio } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.79(d，2H)，8.03(m，1H)，7.75(m，2H)，7.50(m，1H)，7.20(m，1H)，5.55(q，1H)，3.26(s，1H)，2.06(d，3H)，1.18(m，2H)，0.81(m，2H).	660
661			662	2- (5-chloro-2-fluoro-phenyl) -5- [1- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4 ]Triazol-3-ylthio) -ethyl]-[1，3，4]Oxadiazoles as herbicides	8.97(m，1H)，7.59(m，1H)，7.47(m，1H)，7.17(m，1H)，7.12(m，1H)，6.59(m，1H)，5.18(q，1H)，4.21(q，2H)，2.00(d，3H)，1.33(t，3H).
663	2- (5-chloro-2-fluoro-phenyl) -5- {1- [ 4-methyl-5- (2-methyl-thiazol-4-yl) -4H- [1, 2, 4 [ ] -]Triazol-3-ylthio]-ethyl } - [1, 3, 4]Oxadiazoles as herbicides	7.99(s，1H)，7.96(m，1H0，7.48(m，1H)，7.17(t，1H)，7.06(q，1H)，3.86(s，3H)，2.75(s，3H)，1.98(d，3H).	662

664	4- (4-Cyclopropylmethyl-5- {1- [5- (2-fluoro-5-methyl-phenyl) -isoxazol-3-yl]-ethylthio } -4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.78(dd，2H)，7.71(dd，1H)，7.58(dd，2H)，7.25(m，1H)，7.08(m，1H)，6.62(d，1H)，5.12(q，1H)，3.87(dd，2H)，2.40(s，3H)，1.94(d，3H)，0.90(m，1H)，0.49(m，2H)，0.19(m，2H).
664			665	4- (5- {1- [5- (3-fluoro-phenyl) - [1 ]，2，4]Oxadiazol-3-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.78(bs，2H)，7.92(d，1H)，7.80(dd，1H)，7.60(d，2H)，7.50(m，1H)，7.25(m，1H)，5.05(q，2H)，3.65(s，3H)，1.94(d，3H).
666	4- (4-cyclopropyl-5- {1- [5- (3-fluoro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.76(d，2H)，7.95(d，1H)，7.85(dd，1H)，7.75(d，2H)，7.50(m，1H)，7.25(m，1H)，5.45(q，2H)，3.20(m，1H)，1.98(d，3H)1.22(m，2H)，0.88(m，2H).	665
666			667	4- (5- {1- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthio]-ethyl } - [1, 3, 4]Oxadiazol-2-yl) -methyl-pyridines	8.65(d，1H)，7.71(s，1H)，7.63(d，1H)，7.54(d，2H)，7.00(d，2H)，5.10(q，1H)，3.87(s，3H)，3.53(s，3H)，2.58(s，3H)，2.00(d，3H).
668	4- (5- {1- [ 4-Ethyl-5- (4-methoxy-phenyl) -4H- [1, 2, 4]Triazol-3-ylthio]-ethyl } - [1, 3, 4]Oxadiazol-2-yl) -2-methyl-pyridines	8.65(d，1H)，7.71(s，1H)，7.63(d，1H)，7.49(d，2H)，7.01(d，2H)，5.26(q，1H)，3.96(q，2H)，3.88(s，3H)，2.62(s，3H)，2.02(d，3H)，1.24(t，3H).	667

669	4- {5- [1- (4-Ethyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthio) -ethyl]-[1，3，4]Oxadiazol-2-yl } -2-methyl-pyridine	8.79(d，2H)，8.67(d，1H)，7.73(s，1H)，7.65(d，1H)，7.55(d，2H)，5.33(q，1H)，4.08(q，2H)，2.64(s，3H)，2.03(d，3H)，1.30(t，3H).
669			670	4- {5- [1- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthio) -ethyl]-[1，3，4]Oxadiazol-2-yl } -2-methyl-pyridine	8.77(d，2H)，8.68(d，1H)，7.72(m，4H)，5.55(q，1H)，3.24(m，1H)，2.64(s，3H)，2.04(d，3H)，1.16(m，2H)，0.81(m，2H).
671	4- {5- [1- (5-Furan-2-yl-4-methyl-4H- [1, 2, 4 ]]Triazol-3-ylthio) -ethyl ]-[1，3，4]Oxadiazol-2-yl } -2-methyl-pyridine	8.61(d，1H)，7.57(m，3H)，7.08(d，1H)，6.57(d，1H)，5.02(q，1H)，3.70(s，3H)，1.96(d，3H).	670
671			672	2- (3-chloro-phenyl) -5- {1- [ 4-methyl-5- (2-methyl-thiazol-4-yl) -4H- [1, 2, 4]Triazol-3-ylthio]-ethyl } - [1, 3, 4]Oxadiazoles as herbicides	7.99(s，1H)，7.94(m，1H)，7.86(m，1H)，7.48(m，1H)，7.39(m，1H)，5.03(q，1H)，3.82(t，3H)，2.73(d，3H)，1.98(d，3H).
673	3- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.88(s，1H)，8.76(d，1H)，8.00(m，2H)，7.90(d，1H)，7.48(m，3H)，5.14(q，1H)，3.60(s，3H)，2.02(d，3H).	672

674	4- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -2-methyl-pyridine	8.66(d，1H)，7.99(m，1H)，7.88(m，1H)，7.51(m，1H)，7.43(m，2H)，7.34(d，1H)，5.13(q，1H)，3.61(s，3H)，2.63(s，3H)，2.00(d，3H).
674			675	4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.68(dd，2H)，8.05(d，1H)，7.92(d，1H)，7.67(dd，2H)，7.51(d，1H)，7.37(t，1H)5.37(q，1H)，3.18(m，1H)，1.90(d，3H)，1.08(m，2H)，0.74(m，2H).
676	5- (3-chloro-phenyl) -3- {1- [5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylSulfur based radicals]-ethyl } - [1, 2, 4]Oxadiazoles as herbicides	8.01(s，1H)，7.90(d，1H)，7.50(m，3H)，7.38(t，1H)，6.92(d，2H)，4.88(q，1H)3.78(s，3H)，3.47(s，3H)，1.83(d，3H).	675
676			677	4- (5- {1- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-3-yl]-ethylthio } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.70(dd，2H)，8.05(m，1H)，7.67(m，2H)，7.46(m，1H)，7.18(m，1H)，5.41(q，1H)，3.18(m，1H)，1.90(d，3H)，1.08(m，2H)，0.74(m，2H).
678	5- (5-chloro-2-fluoro-phenyl) -3- {1- {5- (4-methoxy-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthio } -ethyl } - [1, 2, 4]Oxadiazoles as herbicides	8.05(m，1H)，7.56(m，3H)，7.21(t，1H)，7.00(m，3H)，5.01(q，1H)，3.85(s，3H)，3.56(s，3H)，1.90(d，3H).	677

679	4- [5- (4-Ethyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazol-2-yl]-2-methyl-pyridine	8.79(d，2H)，8.67(d，1H)，7.75(s，1H)，7.67(d，1H)，7.56(d，2H)，4.82(s，2H)，4.10(q，2H)，2.64(s，3H)，1.39(t，3H).
679			680	4- [5- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4 ] ]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazol-2-yl]-2-methyl-pyridine	8.78(d，3H)，8.68(d，1H)，7.74(m，4H)，4.90(s，2H)，3.30(m，1H)，2.65(s，3H)，1.21(m，2H)，0.84(m，2H).
681	4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-3-ylmethylthio]-4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.79(d，2H)，8.12(m，1H)，7.76(m，2H)，7.57(m，1H)，7.25(m，1H)，4.81(s，2H)，3.31(m，1H)，1.20(m，2H)，0.85(m，2H).	680
681			682	4- [5- (5-Furan-2-yl-4-methyl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 3, 4]Oxadiazol-2-yl]-2-methyl-pyridine	8.66(d，1H)，7.72(s，1H)，7.65(d，1H)，7.60(d，1H)，7.11(d，1H)，6.60(d of d，1H)，4.70(s，2H)，3.80(s，3H)，2.64(s，3H).
683	4- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-ethylthio } -4-cyclopropylmethyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.79(bs，2H)，7.98(m，1H)，7.88(m，1H)，7.51(m，4H)，5.30(q，1H)，3.90(m，2H)，2.05(t，3H)，0.94(ms，1H)，0.50(m，2H)，0.19(m，2H).	682

684	4- (5- {1- [5- (4-fluoro-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthio]-ethyl } - [1, 3, 4]Oxadiazol-2-yl) -2-methyl-pyridine	8.66(d，1H)，7.72(s，1H)，7.60(m，3H)，7.17(m，3H)，5.13(q，1H)，3.57(s，3H)，2.63(s，3H)，2.00(d，3H).
684			685	4- (5- {1- [5- (3-fluoro-phenyl) -4-methyl-4H- [1, 2, 4]Triazol-3-ylthio]-ethyl } - [1, 3, 4]Oxadiazol-2-yl) -2-methyl-pyridines	8.65(d，1H)，7.72(s，1H)，7.66(d，1H)，7.48-7.20(m，4H)，5.15(q，1H)，3.60(s，3H)，2.63(s，3H)，2.01(d，3H).
686	3- [3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-4-fluoro-benzonitrile	8.77(dd，2H)，8.49(dd，1H)，7.90(m，1H)，7.74(dd，2H)，7.43(t，1H)，4.81(s，2H)，3.31(m，1H)，1.21(m，2H)，0.83(m，2H).	685
686			687	4-chloro-2- [3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4-]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-phenol	10.15(bs，1H)，8.77(dd，2H)，7.89(d，1H)，7.75(dd，2H)，7.45(dd，1H)，7.06(d，1H)，4.79(s，2H)，3.29(m，1H)，1.21(m，2H)，0.83(m，2H).
688	4- { 4-cyclopropyl-5- [5- (3-methoxy-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.77(dd，2H)，7.72(m，3H)，7.62(dd，1H)，7.43(t，1H)，7.14(m，1H)，4.77(s，2H)，3.88(s，3H)，3.28(m，1H)，1.17(m，2H)，0.84(m，2H).	687

689	4- { 4-cyclopropyl-5- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4 ] ]Oxadiazol-3-ylmethylthio]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.7(q，2H)，7.81(d，1H)，7.7(q，2H)，7.29(m，1H)，7.1(t，1H)，4.71(s，2H)，3.23(m，1H)，2.32(s，3H)，1.11(m，2H)，0.76(m，2H)
689			690	4- { 4-cyclopropyl-5- [5- (3-fluoro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.67(m，2H)，7.82(m，1H)，7.72(m，1H)，7.66(m，1H)，7.42(m，1H)，7.21(m，1H)，4.68(s，1H)，3.23(m，1H)，1.11(m，2H)，0.75(m，2H)
691	4- [ 4-cyclopropyl-5- (5-m-tolyl- [1, 2, 4 ]]Oxadiazol-3-ylmethylsulfanyl) -4H- [1, 2, 4]Triazol-3-yl]-pyridine	8.69(q，2H)，7.85(m，2H)，7.67(q，2H)，7.32(m，2H)，4.69(s，2H)，3.2(m，1H)，2.35(s，3H)，1.11(m，2H)，0.76(m，2H)	690
691			692	3- [3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-benzonitrile	8.71(b s，2H)，8.36(m，1H)，8.28(d，1H)，7.83(d d，1H) 7.67(m，3H)，4.72(s，2H)，3.23(m，1H)，1.14(m，2H)，0.77(m，2H)
693	4- { 4-cyclopropyl-5- [5- (2, 5-difluoro-phenyl) - [1, 2, 4 ] methyl ethyl]Oxadiazol-3-ylmethylthio]-4H-[1，2，4]Triazol-3-yl } -pyridines	8.75(t，2H)，7.79(m，2H)，7.26(m，2H)，4.78(s，2H)，3.28(m，1H)，1.14(m，2H)，0.82(m，2H)	692

694	4- { 4-cyclopropyl-5- [1- (5-m-tolyl- [1, 2, 4 ]]Oxadiazol-3-yl) -ethylthio]-4H-[1，24]Triazol-3-yl } -pyridines	8.67(dd，2H)，7.87(m，2H)，7.67(dd，2H)，7.33(m，2H)，5.36(q，1H)，3.15(m，1H)，2.36(s，3H)，1.92(d，3H)，1.07(m，2H)，0.72(m，2H)
694			695	4- (4-cyclopropyl-5- {1- [5- (3-methoxy-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.69(m，2H)，7.6(m，3H)，7.52(m，1H)，7.35(t，1H)，7.04(dd，1H)，5.35(q，1H)，3.81(s，3H)，3.15(m，1H)，1.91(d，3H)，1.11(m，2H)，0.7(m，2H)
696	4- {5- [5- (2-chloro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-cyclopropyl-4H [1, 2, 4 ]]Triazol-3-yl } -pyridines	8.69(d，2H)，7.78(m，1H)，7.67(m，2H)，7.35(d，1H)(，7.24(m，1H)，4.72(s，2H)，3.22(m，1H)，2.31(s，3H)，1(m，2H)，0.76(m，2H)	695
696			697	2- [3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4 ]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-4-methyl-phenol	9.89(s，1H)，8.7(m，2H)，7.68(m，3H)，7.2(m，1H)，6.92(d，1H)，4.72(s，2H)，3.22(m，1H)，2.26(s，3H)，1.01(m，2H)，0.74(m，2H)
698	4- (5- {1- [5- (2-chloro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.69(dd，2H)，7.8(q，1H)，7.67(m，2H)，7.35(d，1H)，7.22(m，1H)，5.4(q，1H)，3.16(m，1H)，2.32(s，3H)，1.93(d，3H)，1.09(m，2H)，0.73(m，2H)	697

[0863] Example 699

[0864] {3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -phenyl } -methanol

[0865]Reacting [3- (3-chloromethyl- [1, 2, 4]]Oxadiazol-5-yl) -phenyl]Methanol (32mg, 0.14mmol), 4-methyl-5-thiophen-3-yl-4H- [1, 2, 4]Triazole-3-thiol (41mg, 0.21mmol) and potassium carbonate (29mg, 0.21mmol) were dissolved in anhydrous acetonitrile and refluxed under nitrogen for 1 hour. The solvent was removed in vacuo and the residue was dissolved in NaHCO₃(aq) and extracted with dichloromethane (' 3). The organic phase was dried (MgSO)₄) Filtered and concentrated. Purification by flash chromatography with 3% methanol in dichloromethane afforded the title compound (43mg, 80%) as a colourless oil.¹HNMR(CDCl₃)，δ(ppm)：8.07(s，1H)，7.98(d，1H)，7.60(d，1H)，7.52-7.45(m，3H)，7.16(dd，1H)，5.29(s，2H)，4.75(s，2H)，4.50(s，2H)，3.71(s，1H)。

[0866] The following compounds were prepared in a similar manner to example 699:

example No. 2	Name (R)	1HNMR	MS
example No. 2	Name (R)	1HNMR	MS	700	3- [5- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-3-yl]-phenol
701	5- (3-chloro-phenyl) -3- [4- (tetrahydro-furan-2-ylmethyl) -5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	1.5(m，1H)1.8(m，2H)2.0(m，1H)3.7(m，1H)3.8(m，1H)4.1(s，m，3H)4.5(dd，2H)7.1(dd，1H)7.4(t，2H)7.5(m，2H)7.9(dd，1H)8.0(m，1H	460	700
701			460	702	(2-chloro-phenyl) - {5- [5- (3-chloro-phenyl) - [1, 2, 4]Oxadiazol-3-ylmethylthio]-4-isobutyl-4H- [1, 2, 4 ]Triazol-3-yl } -methanol	0.8(2d, 6H)2.0(m, 1H)3.5(dd, 1H)3.6(dd, 1H)4.5(s, 2H)6.3(d, 1H)7.3(m, 3H)7.5 (clear triplet, 1H)7.6(m, 2H)8.0 (clear d, 1H)8.1(m, 1H)	490

703

5- (2-fluoro-5-methyl-phenyl) -3- [ 5-thiophen-2-yl-4- (2, 2, 2-trifluoro-ethyl) -4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides

2.4(s，3H)4.6(s，2H)4.8(q，J＝7.7Hz，2H)7.1(m，1H)7.2(m，1H)7.4(m，1H)7.5(m，1H)7.6(m，1H)7.8(m，1H)

455.9

[0867] Example 704

[0868]3- (2, 5-difluoro-phenyl) -5- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0869]Reacting 5-chloromethyl-3- (2, 5-difluoro-phenyl) - [1, 2, 4]]Oxadiazole (23mg, 0.10mmol) and 4-Ethyl-5-thiophen-2-yl-2, 4-dihydro- [1, 2, 4]Triazole-3-thione (23mg, 0.11mmol) was dissolved in anhydrous DMF (1ml) and potassium carbonate (21mg, 0.15mmol) was added. After stirring for 22 hours ethyl acetate was added and the resulting mixture was washed twice with water, once with brine and once with MgSO₄Dried and evaporated. Purification by flash chromatography using a 1: 1 heptane to ethyl acetate solution afforded the title compound (20mg, 50%).¹HNMR(CDCl₃)，δ(ppm)：7.64(m，1H)，7.45(d，1H)，7.39(d，1H)，7.10(m，3H)，4.70(s，2H)，4.08(q，2H)，1.32(t，3H)。

[0870] The following compounds were prepared in a similar manner to example 704:

example No. 2	Name (R)	1HNMR	MS
example No. 2	Name (R)	1HNMR	MS	705	5-furan-3-yl-3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4 ]Oxadiazoles as herbicides	3.71(s，3H)4.51(s，2H)6.88(dd，1H)7.17(dd，1H)7.48(dd，1H)7.51(dd，1H)7.54(t，1H)8.18(m，1H)	345.92

706	3- (chloro-phenyl) -5- (5-furan-2-yl-4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	3.78(s，3H)4.64(s，2H)6.57(dd，1H)7.09(d，1H)7.38(t，1H)7.46(m，1H)7.58(d，1H)7.91(d，1H)8.01(m，1H)	373.96
706			373.96	707	3- (3-chloro-phenyl) -5- (5-furan-3-yl-4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	3.63(s，3H)4.64(s，2H)6.85(d，1H)7.39(t，1H)7.47(dt，1H)7.56(t，1H)7.87(br.s，1H)7.91(dt，1H)8.01(t，1H)	373.96
708	5- (3-chloro-phenyl) -3- (5-furan-2-yl-4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	3.77(s，3H)4.50(s，2H)6.55(dd，1H)7.07(d，1H)7.43(t，1H)7.55(m，2H)7.95(dt，1H)8.05(t，1H)	373.96	707			373.96
708			373.96	709	5- (3-chloro-phenyl) -3- (5-furan-3-yl-4-methyl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	3.63(s，3H)4.49(s，2H)6.84(br.s，1H)7.43(t，1H)7.54(m，2H)7.87(s，1H)7.94(d，1H)8.04(m，1H)	373.97
710	4- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyrimidines	4.06(s，3H)4.63(s，2H)7.43(t，1H)7.53(m，1H)7.95(d，1H)8.05(t，1H)8.27(dd，1H)8.85(d，1H)9.25(d，1H)	385.97	709			373.97

711	4- {5- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyrimidines	4.06(s，3H)4.75(s，2H)7.35(t，1H)7.42(ddd，1H) 7.88(dt，1H)7.97(t，1H)8.24(dd，1H)8.84(d，1H)9.23(d，1H)	385.97
711			385.97	712	3- (5-chloro-2-fluoro-phenyl) -5- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	1.29(t，3H)4.07(q，2H)4.68(s，2H)7.08(m，2H)7.35(m，2 H)7.44(dd，1H)7.87(dd，1H)	421.99
713	3- (5-chloro-2-fluoro-phenyl) -5- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	1.32(t，3H)4.18(q，2H)4.71(s，2H)6.51(dd，1H)7.02(dd，1H)7.10(dd，1H)7.37(ddd，1H)7.53(dd，1H)7.91(dd，1H)	406.02	712			421.99
713			406.02	714	5- (chloro-thiophen-2-yl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	1.30(t，3H)4.09(q，2H)4.47(s，2H)6.96(d，1H)7.11(dd，1H)7.40(dd，1H)7.47(dd，1H)7.60(d，1H)	409.92
715	5- (chloro-thiophen-2-yl) -3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4 ]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	1.33(t，3H)4.21(q，2H)4.52(s，2H)6.54(dd，1H)6.98(d，1H)7.05(dd，1H)7.55(dd，1H)7.62(d，1H)	393.96	714			409.92
715			393.96	716	5- (chloro-thiophen-3-yl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	1.36(t，3H)4.12(q，2H)4.58(s，2H)7.15(dd，1H)7.43(m，2H)7.48(dd， 1H)7.94(d，1H)	409.92

717	4- {5- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-ylmethoxy } -phenol	1.30(t，3H)4.02(q，2H)4.51(s，2H)5.07(s，2H)6.72(m，4H)7.39(t，1H)7.49(m，1H)7.89(m，1H)7.99(t，1H)	443.9
717			443.9	718	4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 3, 4%]Oxadiazol-2-ylmethylthio]-4-ethyl-4H- [1, 2, 4]Triazol-3-ylmethoxy } -phenol	1.33(t，3H)4.05(q，2H)4.70(s，2H)5.11(s，2H)6.74(m，4H)7.13(t，1H)7.44(m，1H)7.93(dd，1H)	461.9
719	3- (2, 5-difluoro-phenyl) -5- (4-ethyl-5-furan-2-yl-4H [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	7.75(m，1H)，7.64(d，1H)，7.23(m，2H)，7.16(d，1H)，6.63(dd，1H)，4.80(s，2H)，4.29(q，2H)，1.43(t，3H)	389.9	718			461.9
719			389.9	720	3- (2, 5-difluoro-phenyl) -5- (5-furan-2-yl-4-methyl-4H [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.17(dd，1H)，7.87(m，1H)，7.74(m，2H)，7.33(dd，1H)，6.95(dd，1H)，5.01(s，2H)，3.96(s，3H)	375.8
721	4- (5- {1- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.74(d, 2H), 7.97(s, 1H), 7.87(m, 1H), 7.56(d, 2H), 7.44(m, 1H), 7.36 (significant t, 1H), 5.06(q, 1H), 3.58(s, 3H), 1.96(d, 3H).	400	720			375.8

722	4- {5- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-3-ylmethylthio]-4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl } -pyrimidines	0.90(m，2H)，1.22(m，2H)，3.49(m，1H)，4.81(s，2H)，7.26(t，1H)，7.53(m，1H)，8.11(m，2H)，8.88(d，1H)9.33(s，1H)	430.1
722			430.1	723	2- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl ]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -5-methoxy-pyrimidines	1.32(t，3H)，1.94(d，3H)，4.00(s，3H)，4.50(m，2H)，5.20(q，1H)，7.46(t，1H)，7.56(m，1H)，7.99(d，1H)，8.10(t，1H)，8.56(d，2H).	444.1
724	2- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -pyrimidines	1.34(t，3H)，1.94(d，3H)，4.50(m，2H)，5.26(q，1H)，7.36(t，1H)，7.46(t，1H)，7.57(d，1H)，7.99(m，1H)，8.10(m，1H)，8.92(d，2H).	414	723			444.1
724			414	725	4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -2-methoxy-pyridines	1.32(t，3H)，1.97(d，3H)，3.99(s，3H)，4.06(m，2H)，5.19(q，1H)，6.98(bs，1H)，7.16(m，1H)，7.47(t，1H)，7.58(m，1H)，7.98(dt，1H)，8.10(m，1H)8.31(d，1H).	443.1
726	5- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -2-methoxy-pyridines	1.30(t，3H)，1.96(d，3H)，3.99(m，2H)，4.00(s，3H)，5.16(q，1H)，6.87(d，1H)，7.47(t，1H)，7.58(m，1H)，7.86(dd，1H)，8.00(d，1H)，8.11(t，1H)8.40(d，1H).	443	725			443.1

727	2- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -5-methoxy-pyridines	1.30(t，3H)，1.93(d，3H)，3.92(s，3H)，4.52(m，2H)，5.13(q，1H)，7.32(dd，1H)，7.46(t，1H)，7.56(m，1H)，7.99(dt，1H)，8.10(t，1H)，8.25(d，1H)8.30(d，1H).	443.1
727			443.1	728	3- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -6-methoxy-pyridazine	1.38(t，3H)，1.96(d，3H)，4.20(s，3H)，4.61(m，2H)，5.20(q，1H)，7.12(d，1H)，7.46(t，1H)，7.56(t，1H)，8.00(d，1H)，8.10(s，1H)，8.40(d，1H)	444
729	3- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-yl]-ethylthio } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	0.77(m，2H)，1.14(m，2H)，1.99(d，3H)，3.22(m，1H)，5.44(q，1H)，7.45(m，2H)，7.58(d，1H)，8.02(d，1H)，8.15(m，2H)，8.72(d，1H)9.05(s，1H).		728			444
729				730	4- {5- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-ylmethylthio]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	3.69(s，3H)4.73(s，2H)7.39(t，1H)7.47 (m，1H)7.60(m，2H)7.92(m，1H)8.02(t，1H)8.79(m，2H)	384.91

[0871] Example 731

[0872]5- (3-chloro-phenyl) -3- (5-furan-2-yl-4-isobutyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0873]The title compound was prepared from furan-2-carbohydrazide (55.2mg, 0.44mmol), 1-isothiocyanato-2-methyl-propane (47ml, 0.38mmol) and 3-chloromethyl-5- (3-chloro-phenyl) - [1, 2, 4mmol) according to the method described in Graybill et al Tetrahedron lett.200243, 5305-]Oxadiazole (45.0mg, 0.20mmol) and P-BEMP (136mg, 0.30mmol) as base. Purification by flash chromatography (heptane with 33-66% EtOAc) afforded the product as an oil (12.7mg, 15.6%).¹HNMR(CDCl₃)，δ(ppm)：8.08(s，1H)，7.97(d，1H)，7.55(d，2H)，7.45(t，1H)，7.10(d，1H)，6.56(d，1H)，4.62(s，2H)，4.01(d，2H)，2.03(m，1H)，0.86(d，6H)。

[0874] General method: thiophene-2-carbohydrazide (1.5 equiv.) and isothiocyanate (1.3 equiv.) were dissolved in DMF (1 ml). 2-tert-butylimino-2-diethylamino-1, 3-dimethyl-perhydro-1, 3, 2-didezaphosphorine (1 eq) in polystyrene was added and the reaction was shaken at ambient temperature on a Bohdanminib lock for 1 hour, followed by another 1 hour shaking at 45 ℃. The resin was washed several times with 1: 1 dioxane. Loop closure was performed on a minilock in 1: 1 dioxane: water at 85 ℃ for 48 hours. The resin was washed with acetonitrile (2' 2 ml). 3- (chloromethyl) -5- (3-chlorophenyl) -1, 2, 4-oxadiazole was added to the reaction, shaken in acetonitrile and allowed to stand at 50 ℃ for 2 hours. The product was filtered, purified by MS-directed prep-HPLC over 15 min with a gradient of 0-100% acetonitrile.

[0875] The following compounds are prepared analogously to example 731:

example No. 2	The name of the person to be treated,	1HNMR	MS
example No. 2	The name of the person to be treated,	1HNMR	MS	732	5- (3-chloro-phenyl) -3- [4- (3-methylsulfanyl-propyl) -5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	464.0
733	5- (3-chloro-phenyl) -3- (4-hexyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides		460.0	732		464.0

734	5- (3-chloro-phenyl) -3- (4-cyclopropylmethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	430.0
734		430.0	735	5- (3-chloro-phenyl) -3- [4- (3-fluoro-benzyl) -5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	484.0
736	5- (3-chloro-phenyl) -3- [4- (3-methyl-benzyl) -5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	480.0	735		484.0
736		480.0	737	5- (3-chloro-phenyl) -3- [4- (2-methyl-butyl) -5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	446.0
738	5- (3-chloro-phenyl) -3- [4- (3-methyl-butyl) -5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides	446.0	737		446.0

739

5- (3-chloro-phenyl) -3- [4- (2-fluoro-benzyl) -5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl]-[1，2，4]Oxadiazoles as herbicides

484.0

[0876] Example 740

[0877]5- (3-chloro-phenyl) -3- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-yloxymethyl) - [1, 2, 4] oxadiazole

[0878][5- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-methanol (28.0mg, 0.13mmol), 4-ethyl-3-methanesulfonyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole (35.2mg, 0.13mmol) and cesium carbonate (130mg) were dissolved in dimethylformamide and stirred for 46 hours at ambient temperature under an argon atmosphere. After evaporation to dryness, the crude product is chromatographed on 12g of silica, heptane/ethyl acetate 4/1 to 2/1. The appropriate fractions were collected, evaporated to dryness and dried under vacuum to give the title compound (17.0mg, 33%). 1H NMR (CDCl)₃)，δ(ppm)：8.13(m，1H)，8.02(m，1H)，7.58(m，1H)，7.47(m，2H)，7.40(dd，1H)，7.14(dd，1H)，5.74(s，2H)，4.04(q，2H)，1.38(t，3H)。

[0879] The following compounds were prepared analogously according to example 740:

example No. 2	Name (R)	1HNMR	MS
example No. 2	Name (R)	1HNMR	MS	741	4- {5- [5- (5-chloro-2-fluoro-2-phenyl) - [1, 2, 4 ]]Oxadiazol-3-ylmethoxy radical]-4-methyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines	8.92(s width, 2H), 8.12 (apparent dd, 1H), 7.78(s, 1H), 7.56(s width)2H), 7.25 (apparently t, 1H), 5.79(s, 2H), 3.66(s, 3H).	388

742	4- (5- {1- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-ethoxy } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.82(s width, 2H), 8.07-7.94(m, 2H), 7.69(s width, 2H), 7.47(m, 2H), 6.47(q, 1H), 3.63(s, 3H), 2.02(d, 3H).	384.1
742			384.1	743	4- (5- {1- [3- (3-chloro-phenyl) -isoxazol-5-yl ]-ethoxy } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	1.92(d，3H)，3.57(s，3H)，6.36(q，1H)，6.74(s，1H)，7.39(m，2H)，7.60(m，2H)，7.66(m，1H)，7.78(m，1H)，8.75(m，2H)	383.1
744	3- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-yl]-ethoxy } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines			743			383.1

[0880] The following compounds were prepared analogously to example 740, except that sodium hydride was used as the base and the reaction was heated at 80 ℃:

745

4- {5- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethoxy radical]-4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines

8.77(d，2H)，8.17(s，1H)，8.05(d，1H)，7.79(d，2H)，7.62(dd，1H)，7.52(t，1H)，5.79(s，2H)，3.25(m，1H)，1.14(d，2H)，0.89(m，2H)

746

4- {5- [5- (3-chloro-phenyl) -isoxazol-3-ylmethoxy]-4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl } -pyridines

8.77(d，2H)，7.79(m，3H)，7.7(m，1H)，7.44(m，2H)，6.84(s，1H)，5.71(s，2H)，3.21(m，1H)，1.13(d，2H)，0.82(m，2H)

[0881] Example 747

[0882]5- (2-methoxy-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0883]HBTU (171mg, 0.45mmol) and HOBT (8mg, 0.06mmol) were added to a solution of 2-methoxybenzoic acid (68mg, 0.45mmol) and DIPEA (192ml, 1.11mmol) in DMF (3 ml). After 10 minutes, N-hydroxy-2- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanyl) -acetamidine (100mg, 0.37 mmol). The reaction mixture was stirred at room temperature for 7 hours and then at 110 ℃ overnight. After cooling, the reaction mixture was diluted with water and CH₂Cl₂And (4) extracting. The organic phase was concentrated by drying. Flash chromatography (heptane/EtOAc 1: 2) afforded 1.9mg (11%) of the desired product.

[1667]1H NMR(CDCl₃)，δ(ppm)：7.99(m，1H)，7.53(m，1H)，7.50(m，1H)，7.47(m，1H)，7.16(m，1H)，7.04(m，2H)，4.52(s，2H)，3.94(s，3H)，3.71(s，3H)。

[0884] The following compounds were prepared analogously according to example 747:

example No. 2	Name (R)	1HNMR	MS
example No. 2	Name (R)	1HNMR	MS	748	5-furan-2-yl-3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	3.72(s，3H)4.52(s，2H)6.61(dd，1H)7.16(dd，1H)7.30(dd，1H)7.47(dd，1H)7.50(dd，1H)7.67(dd，1H)	345.92

749	3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-benzoic acid methyl ester	414.0
749		414.0	750	5- (2-fluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	374.0
751	5- (2, 5-difluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	392.0	750		374.0
751		392.0	752	3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-ylsulfanylmethyl) -5- (3-vinyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	382.1
753	5- (3-difluoromethoxy-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	422.0	752		382.1

754	5- (4-methoxy-thiophen-3-yl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	392.0
754		392.0	755	5- (2-chloro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazoles as herbicides	390.0
756	5- (4-fluoro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-ylthiomethyl) - [1, 2, 4 ]Oxadiazoles as herbicides	374.0	755		390.0

[0885] Example 757

[0886]3- (3-chloro-phenyl) -5- [1- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanyl) -ethyl ] - [1, 2, 4] oxadiazole

[0887]Adding 2- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] DMF at room temperature]A mixture of triazol-3-ylsulfanyl) -propionic acid (50mg, 0.186mmol), 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDCI) (35.7mg, 0.186mmol), 1-hydroxybenzotriazole Hydrate (HOBT) (28.5mg, 0.186mmol) and 3-chloro-N-hydroxy-benzamidine (29.3mg, 0.172mmol) was stirred overnight. The reaction mixture was diluted with ethyl acetate (75ml), washed 3 times with water, once with 1.0M HCl (30ml), saturated NaHCO₃(30ml) and saturated brine (30ml), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. DMF (1ml) was added to the residue and the resulting solution was heated at 135 ℃ for 3 h to give cyclization to give oxadiazole. After cooling, the reaction mixture was diluted with ethyl acetate (75ml), washed 3 times with water, once with 1.0M HCl (30ml), saturated NaHCO₃(30ml) and saturated brine (30ml), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The title compound (46.5mg, 66.9%) was purified by SPE chromatography on silica gel using 50ml 40%, 150ml 50% ethyl acetate in hexane. 1HNMR (CDCl) ₃)，δ(ppm)：8.03(s，1H)，7.92(m，1H)，7.47(m，4H)，7.18(dd，1H)，4.99(q，IH)，3.64(s，3H)，1.97(d，3H)。

[0888] The following compounds were prepared analogously according to example 757:

example No. 2	Name (R)	1HNMR	MS
example No. 2	Name (R)	1HNMR	MS	758	3- (5- {1- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.88(d，1H)，8.76(dd，1H)，8.03(m，2H)，7.93(d，1H)，7.74(m，3H)，5.09(m，1H)，3.58(s，3H)，2.00(d，3H)

[0889] The following compounds were prepared analogously according to example 10:

example No. 2	Name (R)
example No. 2	Name (R)	759	5- (1-chloro-ethyl) -3- (3-chloro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides
	3- (1-chloro-ethyl) -5-m-tolyl- [1, 2, 4]Oxadiazoles as herbicides	759
		761	3- (1-chloro-ethyl) -5- (3-methoxy-phenyl) - [1, 2, 4]Oxadiazoles as herbicides
762	3- (1-chloro-ethyl) -5- (2-chloro-5-methyl-phenyl) - [1, 2, 4]Oxadiazoles as herbicides	761
762		763	3- (1-chloro-ethyl) -5- (2, 5-difluoro-phenyl) - [1, 2, 4]Oxadiazoles as herbicides
764	3- (1-chloro-ethyl) -5- (2-fluoro-5-methylphenyl) - [1, 2, 4]Oxadiazoles as herbicides	763
764		765	3- [3- (1-chloro-ethyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-benzonitrile

[0890] The following compounds were prepared analogously according to example 40:

example No. 2	Name (R)	1HNMR	MS
example No. 2	Name (R)	1HNMR	MS	766	4- (5- {1- [5- (2-chloro-5-methyl-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4-methyl-4H [1, 2, 4]Triazol-3-yl) -pyridines	8.74(d，2H)，7.79(s，1H)，7.57(dd，2H)，7.38(d，1H)，7.25(d，1H)，5(q，1H)，3.62(s，3H)，2.33(s，3H)，1.92(d，3H)
767	4- (5- {1- [5- (2, 5-difluoro-phenyl) - [1, 2, 4 ]]Oxadiazol-3-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.67(d，2H)，7.7(m，1H)，7.57(dd，2H)，7.2(m，2H)，5(q，1H)，3.61(s，3H)，1.87(d，3H)		766
767				768	4- (5- {1- [5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4 ] ]Oxadiazol-3-yl]-ethylthio } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.77(d，2H)，7.85(m，1H)，7.61(m，2H)，7.38(m，1H)，7.06(t，1H)，5.02(q，1H)，3.66(s，3H)，2.37(s，3H)，1.94(d，3H)
769	4- (4-cyclopropyl-5- {1- (5- (2-fluoro-5-methyl-phenyl) - [1, 2, 4]]Oxadiazol-3-yl) -ethylsulfanyl } -4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.75(d，2H)，7.9(m，1H)，7.74 (m，2H)，7.38(m，1H)，7.13(m，1H)，5.45(q，1H)，3.24(m，1H)，2.39(s，3H)，2(d，3H)，1.15(m，2H)，0.79(m，2H)		768

770	3- {3- [1- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4]]Triazol-3-ylthio) -ethyl]-[1，2，4]Oxadiazol-5-yl } -benzonitrile	8.76(dd，2H)，8.4(s，1H)，8.32(d，1H)，7.87(d，1H)，7.65(t，1H)，7.59(m，2H)，5.07(q，1H)，3.67(s，3H)，2.59(s，2H)，1.91(d，3H)
770			771	3- {3- [1- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4]]Triazol-3-ylthio) -ethyl]-[1，2，4]Oxadiazol-5-yl } -benzonitrile	8.77(m，2H)，8.42(d，1H)，8.38(m，1H)，7.9(m，1H)，7.71(m，3H)，5.49(q，1H)，3.25(m，1H)，2(d，3H)，1.17(m，2H)，0.81(m，2H)
772	3- {1- [5- (3-chloro-phenyl) - [1, 3, 4]]Oxadiazol-2-yl]-ethylsulfanyl } -5-pyridin-4-yl- [1, 2, 4]Triazol-4-ylamines	8.77(br s，2H)，8.18(d，2H)，7.98(s，1H)，7.87(d，1H)，7.52(d，1H)，7.44(t，1H)，5.66(s，2H)，4.88(q，1H)，1.98(d，3H)	771

[0891] The following compounds were prepared in analogy to example 316.

Example No. 2	Name (R)
Example No. 2	Name (R)	773	3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-2-methyl-propionylhydrazine
774	Rac-3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-butyryl hydrazine	773

[0892] The following compounds were prepared according to a similar method to that of example 318.

Example No. 2	Name (R)
Example No. 2	Name (R)	775	2- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-cyclopropanecarboxylic acid hydrazide

[0893] Example 776

[0894]3- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -2, 2-dimethyl-propionylhydrazine

[0895] 3, 3-dimethyl-dihydro-furan-2, 5-dione (6.4g) was heated in ethanol (150mL) at 50 ℃ overnight. The solvent was removed in vacuo and the residue triturated with hexanes to give 4-ethyl 2, 2-dimethyl-succinate (4.66g), which was used without further purification. tert-Butanol (7.5mL) was added to a mixture of 4-ethyl 2, 2-dimethyl-succinate (2.74g, 15.7mmol) in dichloromethane (62mL) containing magnesium sulfate (7.5g) and concentrated sulfuric acid (0.85mL), and the mixture was stirred at room temperature overnight. Saturated sodium bicarbonate solution was added and the product was extracted with dichloromethane, washed with brine solution, dried and concentrated to give the diester (1.89g) as a colorless oil. The crude sample was treated with a mixture of ethanol (50mL) and water (25mL) containing potassium hydroxide (2.75g) at room temperature for 2 hours to hydrolyze the ethyl ester. The reaction was acidified with 1N HCl (aq), extracted with ether, dried and concentrated to give 1-tert-butyl 2, 2-dimethyl-succinate (1.4 g). The acid was treated under the conditions of example 320 (step 1) to give tert-butyl 3- [3- (3-fluorophenyl) - [1, 2, 4] oxadiazol-5-yl ] -2, 2-dimethyl-propionate (1.9 g). The tert-butyl ester was deprotected by treatment with formic acid (19mL) for 20 min at 50 ℃. The crude product is concentrated and triturated with a mixture of diethyl ether and hexane to give 3- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -2, 2-dimethyl-propionic acid. To a solution of 3- [3- (3-chlorophenyl) - [1, 2, 4] oxadiazol-5-yl ] -2, 2-dimethylpropanoic acid (561mg, 2mmol) and triethylamine (1.1mL, 8mmol) in THF (9mL) at-78 deg.C was added isobutyl chloroformate (0.31mL, 2.4mmol) dropwise. After stirring for 1 hour, hydrazine hydrate (1mL, 11mmol) was added. The reaction mixture was stirred at room temperature for 1 hour and concentrated. Any excess reaction was quenched by the addition of a small amount of ice and the product precipitated and was collected by filtration to yield 482mg of the title compound.

[0896] The following compounds were prepared in analogy to example 320.

Example No. 2	Name (R)
Example No. 2	Name (R)	777	(S) - {1- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-2-Hydrazinocarbonyl-ethyl } -carbamic acid tert-butyl ester

[0897] Example 778

[0898]3- (3-chloro-phenyl) -5- [2- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-yl) -ethyl ] - [1, 2, 4] oxadiazole

[0899]Step 1: 3- [3- (3-chlorophenyl) - [1, 2, 4]]Oxadiazol-5-yl]-propionic acid (b)Ethoxy-thiophen-2-yl-methylene) -hydrazide: reacting 3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-propionohydrazide (266.9mg, 1mmol) was mixed with ethyl thiophene-2-hydroxamate (191.6mg, 1mmol) in ethanol (6ml) and stirred at room temperature overnight. The reaction was quenched with water, extracted with ethyl acetate, dried and concentrated in vacuo. The crude product was triturated with hexane to give 3- [3- (3-chloro-phenyl) - [1, 2, 4] as a white solid]Oxadiazol-5-yl]-propionic acid (ethoxy-thiophen-2-yl-methylene) -hydrazide (305mg, 75%).¹H-NMR(CDCl₃) δ (ppm): 8.99(ws, 1H), 8.09(s, 1H), 7.98(d, 1H), 7.41(m, 4H), 7.08(dd, 1H), 4.27(q, 2H), 3.34(m, 4H) and 1.41(t, 3H). Step 2: 3- (3-chloro-phenyl) -5- [2- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4 ]Triazol-3-yl) -ethyl]-[1，2，4]Oxadiazole: reacting 3- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-propionic acid (ethoxythiophen-2-yl-methylene) -hydrazide (81mg, 0.2mmol) was mixed with 2M methylamine (0.3 ml in THF) in ethanol (2ml) at 70-80 ℃ overnight. The reaction mixture was concentrated with silica gel and purified by column chromatography using ethyl acetate containing 0.5 to 2.0% methanol to give 54mg (72.5%) of 3- (3-chloro-phenyl) -5- [2- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4)]Triazol-3-yl) -ethyl]-[1，2，4]An oxadiazole.¹H-NMR(CDCl₃)δ(ppm)：8.08(s，1H)，7.97(d，1H)，7.41(m，4H)，7.20(dd，IH)，3.80(s，3H)，3.68(dd，2H)，3.38(dd，2H)。

[0900] The following compounds were prepared according to a similar method to example 778.

Example No. 2	Name (R)	1H NMR	MS
Example No. 2	Name (R)	1H NMR	MS	779	3- (3-chloro-phenyl) -5- [2- (4-ethyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazol-3-yl) -ethyl]-[1，2，4]Oxadiazoles as herbicides	8.08(s, 1H), 7.97(d, 1H), 7.47(m, 4H), 7.20(dd, 1H), 4.20(q, 2H), 3.72(dd, 2H), 3.38(dd, 2H) and 1.47(t, 3H)
780	5- (3-chloro-phenyl) -3- (5-furan-2-yl-4-methyl-4H- [1, 2, 4]Triazol-3-ylmethyl) - [1, 2, 4]Oxadiazoles as herbicides	8.11(s, 1H), 8.01(d, 1H), 7.61(s, 1H), 7.58(d, 1H), 7.48(t, 1H), 7.11(d, 1H), 6.59(m, 1H), 4.48(s, 2H) and 3.92(s, 3H)		779
780				781	2- (3-chloro-phenyl) -5- [2- (5-furan-2-yl-4-methyl-4H- [1, 2, 4 ]Triazol-3-yl) -ethyl]-[1，3，4]Oxadiazoles as herbicides	8.04(s, 1H), 7.93(d, 1H), 7.60(s, 1H), 7.52(d, 1H), 7.46(t, 1H), 7.06(d, 1H), 6.59(m, 1H), 3.87(s, 3H), 3.65(t, 2H) and 3.38(t, 2H)
782	2- (3-chloro-phenyl) -5- [2- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4]Triazol-3-yl) -ethyl]-[1，3，4]Oxadiazoles as herbicides	8.05(s, 1H), 7.94(d, 1H), 7.60(s, 1H), 7.52(d, 1H), 7.47(t, 1H), 7.10(d, 1H), 6.59(m, 1H), 4.30(q, 2H), 3.67(t, 2H), 3.39(t, 2H) and 1.43(t, 3H)		781

783

2- (3-chloro-phenyl) -5- [2- (4-cyclopropyl-5-furan-2-yl-4H- [1, 2, 4]Triazol-3-yl) -ethyl]-[1，3，4]Oxadiazoles as herbicides

8.05(s, 1H), 7.94(d, 1H), 7.63(s, 1H), 7.52(d, 1H), 7.46(t, 1H), 7.01(d, 1H), 6.58(m, 1H), 3.67(dd, 2H), 3.51(t, 2H), 3.33(m, 1H)1.25(m, 2H) and 0.93(m, 2H)

383.12

[0901] Example 784

[0902]4- (5- {2- [3- (3-chlorophenyl) - [1, 2, 4] oxadiazol-5-yl ] -ethyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine

[0903] Step 1: isonicotinic acid {4- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -1-ethoxy-butylidene } -hydrazide: ethyl 3- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -alaninate hydrochloride (473.3mg, 1.5mmol) and a solution of isonicotinyl hydrazide (205.7mg, 1.5mmol) in ethanol (8ml) were mixed at 60 ℃ for 1 hour and then at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane and washed with water. The organic layer was dried, concentrated in vacuo, and the residue triturated with ether to give 490mg (78.9%) of isonicotinic acid {4- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -1-ethoxy-butylidene } -hydrazide as a white solid.

[0904]Step 2: by isonicotinic acid {4- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-1-ethoxy-butylidene } -hydrazide (60mg, 0.15mmol) and a solution of 2M methylamine (0.45ml, 0.9mmol) in ethanol (1ml) were reacted at 60 ℃ overnight to give 4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ] as a white solid]Oxadiazol-5-yl]-ethyl } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridine (47.1mg, 82%).¹H-NMR(CDCl₃) δ (ppm): 8.77(d, 2H), 8.02(s, 1H), 7.91(d, 2H), 7.58(d, 2H), 742 (m, 2H), 3.76(s, 3H), 3.66(t, 2H) and 3.38(t, 2H).

[0905] The following compounds were prepared according to a similar method to example 784.

Example No. 2	Name (name)Balance	1HNMR	MS
Example No. 2	Name (name)Balance	1HNMR	MS	785	4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-ethyl } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.79(d, 2H), 8.05(s, 1H), 7.94(d, 1H), 7.58(d, 2H), 7.43(m, 2H), 4.16(q, 2H), 3.72(t, 2H), 3.40(t, 2H) and 1.44(t, 3H)
786	4- (5- {2- [3- (3-chlorophenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-ethyl } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.77(d, 2H), 8.05(s, 1H), 7.93(d, 1H), 7.73(d, 2H), 7.44(m, 2H), 3.72(t, 3H), 3.51(t, 2H), 3.38(m, 1H), 1.23(m, 2H) and 0.79(m, 2H)		785

[0906] Example 787

[0907]4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -propyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine

[0908]Step 1: n-cyclopropyl-isonicotinamide: ethylisonicotinic acid (3.0g, 20mmol) was reacted with ethyl isonicotinate (N-acetyl-L-D) at 120 ℃ in a sealed glass bottleCyclopropylamine (2ml) was mixed for 40 hours. The reaction mixture was triturated with ether to give 1.62g (50%) of N-cyclopropyl-isonicotinamide as an off-white solid.¹H-NMR(CDCl₃) δ (ppm): 8.73(d, 2H), 7.60(d, 2H) and 6.55(w, 1H), 2.92(m, 1H), 0.90(m, 2H) and 0.66(m, 2H). Step 2: n-cyclopropyl-isonicotinimoyl chloride hydrochloride: n-cyclopropyl-isonicotinamide (1.62g, 10mmol) was reacted with SOCl₂(12g, 100mol) were treated at 80 ℃ overnight. The reaction mixture was concentrated and triturated with dichloromethane to give 1.3g (64%) of N-cyclopropyl-isonicotinimoyl chloride hydrochloride as a yellow solid step 3: 4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-propyl } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridine: (R) -3- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]Butyryl hydrazine (56mg, 0.2mmol) with N-cyclopropyl-isonicotinimoyl chloride hydrochloride (40.6mg, 0.2mmol) and K₂CO₃(60mg, 0.43mmol) was mixed in DMF (1ml) at 100 ℃ for 3 h. The reaction mixture was diluted with dichloromethane and then washed with water. The organic layer was concentrated and purified with an ethyl acetate solution containing 5-6% methanol to yield 32mg (39%) of the title compound. ¹H-NMR(CDCl₃) δ (ppm): 8.78(d, 2H), 8.05(s, IH), 7.96(d, IH), 7.73(d, 2H), 7.45(m, 2H), 4.15(q, 1H), 3.64(dd, 1H), 3.31(m, 2H), 1.68(d, 3H), 1.25(m, 2H) and 0.79(m, 2H).

[0909] The following compounds were prepared in analogy to example 787: it is noted that some reactions provide 1, 3, 4-oxadiazole cyclization products without methylamino or cyclopropylamine instead of or in addition to triazole products.

Example No. 2	Name (R)	1H NMR	MS
Example No. 2	Name (R)	1H NMR	MS	788	4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-2-methyl-propyl } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.74(d, 2H), 8.04(s, 1H), 7.94(d, 1H), 7.67(d, 2H), 7.43(m, 2H), 3.48(s, 2H), 3.09(m, 1H), 1.75(s, 6H), 1.16(m, 2H) and 0.68(m, 2H)
789	4- (5- {2- [5- (3-chloro-phenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-propyl } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.76(w, 2H), 8.03(s, 1H), 7.92(d, 1H), 7.72(d, 2H), 7.44(m, 2H), 4.13(m, 1H), 3.72(dd, 1H), 3.43(m, 1H), 3.27(dd, 1H), 1.66(d, 3H), 1.25(m, 2H) and 0.79(m, 2H)		788
789				790	4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-1-methyl-ethyl } -4-cyclopropyl-4H- [1, 2, 4 ]Triazol-3-yl) -pyridines	8.78(d，2H)，8.01(s，1H)，7.91(d，1H)，7.73(d，2H)，7.49(d，1H)，7.42(t，1H)，3.99(m，1H)，3.83(dd，1H)，3.48(m，1H)，3.39(m，1H)，1.61(d，3H)，1.25(m，2H)，0.98(m，1H)，0.74(m，1H)

791	Cis 4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-cyclopropyl } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.73(d，2H)，7.88(s，1H)，7.78(d，1H)，7.65(d，2H)，7.41(d，1H)，7.34(t，1H)，3.20(m，1H)，2.89(m，2H)，2.54(dd，1H)，2.00(td，1H)，1.20(m，2H)，0.83(m，2H)
791			792	4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-1, 1-dimethyl-ethyl } - [1, 3, 4]Oxadiazol-2-yl) -pyridines	8.82 (m，2H)，7.98(s，1H)，7.90(m，3H)，7.47(d，1H)，7.39(t，1H)，3.51(s，2H)，1.70(s，6H)
793	4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-2-methyl-propyl } - [1, 3, 4]Oxadiazol-2-yl) -pyridines	8.76(d，2H)，8.07(s，1H)，7.97(d，1H)，7.77(d，2H)，7.49(dd，1H)，7.43(t，1H)，3.53(s，2H)，1.69(s，6H)	792
793			794	4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-1-methyl-ethyl } - [1, 3, 4]Oxadiazol-2-yl) -pyridines	8.82(d，2H)，8.05(m，1H)，7.95(d，1H)，7.91(d，2H)，7.50(dd，1H)，7.42(t，1H)，3.94(dd，1H)，3.67(dd，1H)，3.41(dd，1H)，1.66(d，3H)
795	4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-cyclopropyl } - [1, 3, 4]Oxadiazol-2-yl) -pyridines	8.77(d，2H)，7.81(m，4H)，7.42(d，1H)，7.32(t，1H)，3.07(q，1H)，2.99(q，1H)，2.41(q，1H)，2.08(td，1H)	794
795			796	4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-cyclopropyl } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.76(d，2H)，7.85(m，1H)，7.77(d，1H)，7.55(d，2H)，7.44(dd，1H)，7.34(t，1H)，3.70(s，3H)，2.89(m，1H)，2.72(m，1H)，2.51(q，1H)，2.02(dt，1H)

797	4- (5- {2- [5- (3-chlorophenyl) - [1, 3, 4 ]]Oxadiazol-2-yl]-propyl } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.79(d，2H)，8.02(s，1H)，7.93(d，1H)，7.59(d，2H)，7.53(d，1H)，7.46(t，1H)，4.03(m，1H)，3.80(s， 3H)，3.52(m，1H)，3.23(dd，1H)，1.66(d，3H)
797			798	4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-propyl } - [1, 3, 4]Oxadiazol-2-yl) -pyridines	8.81(d，2H)，8.07(s，1H)，7.97(d，1H)，7.87(d，2H)，7.50(d，1H)，7.43(t，1H)，3.91(q，1H)，3.66(dd，1H)，3.44(dd，1H)，1.65(d，3H)
799	4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-propyl } -4-methyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.80(d，2H)，8.05(s，1H)，7.95(d，1H)，7.61(d，2H)，7.51(d，1H)，7.45(t，1H)，4.07(q，1H)，3.75(s，3H)，3.48(dd，1H)，3.23(dd，1H)，1.68(d，3H)	798
799			800	4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl ]-propyl } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridines	8.78(d，2H)，8.05(s，1H)，7.96(d，1H)，7.74(d，2H)，7.50(dd，1H)，7.46(t，1H)，4.15(q，1H)，3.64 (dd，1H)，3.31(m，2H)，1.67(d，3H)，1.25(m，2H)，0.81(m，2H)
801	(S) - [1- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-2- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4]Triazol-3-yl) -ethyl]-carbamic acid tert-butyl ester		800

[0910] Example 802

[0911] (S) -1- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -2- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -ethylamine

[0912](S) - [1- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-2- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4]Triazol-3-yl) -ethyl]Tert-butyl carbamate (135mg) was mixed with 96% formic acid (1.3mL) and heated at 50 ℃ for 1 hour. The reaction mixture was concentrated in vacuo. The residue was quenched with saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated. Purification by flash column silica gel chromatography with 2-3% (2M ammonia methanol) in dichloromethane afforded 106 mg of the title compound as an off-white solid.¹HNMR(CDCl₃)：δppm 8.73(d，2H)，8.03(s，IH)，7.93(d，1H)，7.69(d，2H)，7.46(d，1H)，7.42(t，1H)，5.02(dd，1H)，3.61(dd，1H)，3.49(dd，1H)，3.35(m，1H)，2.47(br s，2H)，1.20(m，2H)，0.75(m，2H)

[0913] Example 803

[0914] (S) - [1- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -2- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -ethyl ] -dimethyl-amine

[0915] Sodium cyanoborohydride (0.1mL, 1M in THF) was added to a solution of (S) -1- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -2- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -ethylamine (30mg) in methanol (0.8mL) containing 96% formic acid (0.1mL) and 37% formalin solution (0.1 mL). The residue was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated. Purification by flash column silica gel chromatography with 3% (2M ammonia methanol) in dichloromethane afforded 22 mg of the title compound.

¹H NMR(CDCl₃)：δppm 8.76(d，2H)，8.06(s，1H)，7.97(d，1H)，7.73(d，2H)，7.47(d，IH)，7.45(t，1H)，5.00(dd，1H)，3.76(dd，1H)，3.51(dd，1H)，3.42(m，1H)，2.45(br s，6H)，1.26(m，2H)，0.88(m，1H)，0.79(m，1H)

[0916] Example 804

[0917]8- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyridine

[0918]37mg (0.25mmol) of Me₃OBF₄60mg (0.21mmol) of 3- [5- (3-chloro-phenyl) - [1, 2, 4] are added]Oxadiazol-3-ylmethyl]Piperidin-2-one in 2ml CH₂Cl₂The solution of (1). The mixture was stirred at room temperature overnight. By CH₂Cl₂The reaction mixture was diluted with NaHCO₃(saturated) washed, dried and concentrated. The residue was dissolved in 3ml EtOH and 22mg (0.16mmol) of isonicotinyl hydrazide were added. The solution was heated with a microwave at 120 ℃ for 10 minutes. The reaction mixture was cooled and the volatiles were removed under reduced pressure. The crude product was purified by preparative HPLC to provide 17mg (20%) of the desired product.¹H NMR(CDCl₃)：δppm 1.75(m，1H)1.99(m，1H)2.21(m，2H)3.16(dd，1H)3.73(m，1H)3.85(dd，1H)4.07(m，1H)4.19(m，1H)7.47(t，1H)7.56(m，1H)7.67(m，2H)8.01(m，1H)8.11m，1H)8.76(d，2H)。

[0919] The following compounds were prepared in analogy to example 804:

example No. 2	Name (R)	1HNMR	MS
example No. 2	Name (R)	1HNMR	MS	805	8- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethyl]-3-thiophen-2-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4]Triazole [4, 3-a ]]Pyridine compound	1.69(m，1H)1.99(m，1H)2.18(m，2H)3.11(m，1H)3.67(m，1H)3.87(m，1H)4.02(m，1H)4.24(m，1H)7.15(m，1H)7.47(m，3H)7.56(m，1H)8.01(d，J＝7.83Hz，1H)8.12(d，J＝1.77Hz，1H)
806	8- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethyl]-3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4]Triazole [4, 3-a ]]Pyridine compound	1.76(m，1H)2.00(m，1H)2.21(m，2H)3.22(dd，，1H)3.74(m，1H)3.87(dd，1H)4.09(m，1H)4.19(m，1H)7.23(m，1H)7.53(m，1H)7.68(m，2H)8.10(dd，1H)8.77(m，2H)		805

[0920] Example 807

[0921]5- (5-bromo-4-methyl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -3- (3-chloro-phenyl) - [1, 2, 4] oxadiazole

[0922]3- (3-chloro-phenyl) -5- (4-methyl-4H- [1, 2, 4)]Triazol-3-ylthiomethyl) - [1, 2, 4]The oxadiazole was mixed with 30ml of chloroform/pyridine (25/l) solution at room temperature. A solution of bromine in chloroform (0.5ml) was then added dropwise and the reaction mixture was heated at 70 ℃ overnight. The reaction mixture was diluted with chloroform and saturated NH₄Cl was washed twice, the organic layer was dried over sodium sulfate, concentrated, and the residue was triturated with diethyl ether to give the title compound (1.5g, 57.5%, yellow solid).¹H-NMR(CDCl₃) δ (ppm): 8.05(s, 1H), 7.94(d, 1H), 7.47(d, 1H), 7.43(t, 1H), 4.66(s, 2H) and 3.59(s, 3H).

[0923] Example 808

[0924]3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazol-5-yl ] -aniline

[0925]To {3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] at 0 DEG C]Triazol-3-ylthiomethyl) [1, 2, 4]]Oxadiazol-5-yl-phenyl]-tert-butyl carbamate (88.0mg, 0.19mmol) in dichloromethane (3ml) TFA (1.5ml) was added and stirred for 1 hour. The reaction mixture was warmed to room temperature and the solvent was removed in vacuo. To the resulting residue was added dichloromethane, the mixture was cooled to 0 ℃, saturated sodium bicarbonate was added and stirred until the solution became basic (pH 8). The mixture was then transferred to a separatory funnel, extracted with dichloromethane, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue obtained is triturated with ether and isolated to yield 61.1mg (87%) of 3- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4] ]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]Aniline (light yellow solid).¹HNMR(DMSO-d6)δ(ppm)：7.81(d，1H)，7.64(d，1H)，7.23(m，4H)，6.84(d，1H)，5.57(s，2H)，4.50(s，2H)，3.72(s，3H)。

[0926] The following compounds were prepared in analogy to example 98:

example No. 2	Name (R)	1HNMR	MS
example No. 2	Name (R)	1HNMR	MS	809	5- (3-chloro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-sulfonylmethyl- [1, 2, 4]Oxadiazoles as herbicides	423.01
810	5- (3-chloro-phenyl) -3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]Triazole-3-sulfinylmethyl- [1, 2, 4 [ ]]Oxadiazoles as herbicides			809		423.01

[0927] The following compounds were prepared in analogy to example 93:

example No. 2	Name (R)	1HNMR	MS
example No. 2	Name (R)	1HNMR	MS	811	2-methyl-6- [3- (4-methyl-5-thiophen-2-yl-4H- [1, 2, 4]]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]-pyridine

[0928] Example 812

[0929]4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -ethylsulfanyl } -4-ethyl-4H- [1, 2, 4] triazol-3-yl) -pyridin-2-ol

[0930]HBr (1ml) and HOAc (1ml) were added to 4- (5- {1- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-yl]-ethylthio } -4-ethyl-4H- [1, 2, 4]Triazol-3-yl) -2-methoxy-pyridine (9mg, 0.02mmol) was stirred at 80 ℃. Saturated NaHCO was added to the reaction₃(aq.) the mixture was extracted three times with dichloromethane. The combined organic phases were dried and concentrated to give the title compound (8.5mg, 99%). ¹H NMR(CDCl₃)，δ(ppm)：1.37(t，3H)，1.96(d，3H)，4.10(q，2H)，5.23(q，1H)，6.80(m，2H)，7.49(t，2H)，7.59(m，1H)，7.99(d，1H)，8.11(s，1H)。

Example 813

[0931]4- (5- {2- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-yl ] -propyl } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine

[0932]84 microliters (0.21mmol, 2.5M) of n-BuLi were added dropwise to 37mg (0.21mmol) of 4- (4, 5-dimethyl-4H- [1, 2, 4] at 0 DEG C]Triazol-3-yl) -pyridine in 2.1ml THF solution. After 20 min, 60mg (0.21mmol) of 3- (1-bromo-ethyl) -5- (3-chloro-phenyl) - [1, 2, 4] are added dropwise]Oxadiazole solution. The reaction mixture was stirred at room temperature overnight. Addition of NH₄Cl (saturated) and the mixture was then extracted twice with EtOAc. The organic phase was dried and concentrated. Flash Chromatography (CH)₂Cl₂MeOH 20: 1) gave 7.7mg (10%) of the desired product.¹HNMR(CDCl₃)，δ(ppm)：1.57(d，3H)3.16(m，1H)3.38(m，1H)3.71(s，3H)3.84(d，1H)7.46(t，1H)7.55(m，1H)7.58(m，2H)7.98(m，1H)8.10(t，1H)8.77(d，2H)。

[0933] Example 814

[0934] [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -methyl- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -amine

[0935]Under nitrogen, 10mg (0.4mmol) NaH are added to 38mg (0.2mmol) methyl- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4)]Solution of triazol-3-yl) -amine in 3ml DMF. After 10 min 50mg (0.22mmol) of 3-chloromethyl 5- (3-chloro-phenyl) - [1, 2, 4] are added]A solution of oxadiazole in 2ml DMF. After stirring for 45 minutes, NH was added₄Cl (saturated) and CHCl₃The mixture was extracted twice. The organic phase was dried and concentrated. Flash Chromatography (CH) ₂Cl₂MeOH 20: 1) gave 41mg (54%) of the desired product.¹HNMR(CDCl₃)，δ(ppm)：3.07(s，3H)3.71(s，3H)4.56(s，2H)7.45(m，1H)7.55(m，1H)7.62(d，2H)7.98(d，1H)8.09(m，1H)8.73(d，2H)。

Example 815

[0936]8- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethyl ] -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrimidine

[0937]32mg (1.31mmol) of NaH are added to 193mg (0.96mmol) of 3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4] at room temperature]Triazole [4, 3-a ]]Solutions of pyrimidine in 10ml DMF. After 10 min, 200mg (0.87mmol) of 5- (3-chloro-phenyl) -3-chloromethyl- [1, 2, 4]Oxadiazole was added to the reaction mixture. The reaction mixture was stirred at room temperature overnight. By NH₄The reaction mixture was diluted with Cl (sat) and extracted twice with EtOAc. The combined organic phases were washed with water, dried and concentrated. Flash Chromatography (CH)₂Cl₂MeOH 20: 1) gave 111mg (32%) of a white solid.¹H NMR(CDCl₃)，δ(ppm)：2.24(m，2H)3.57(m，2H)4.15(m，2H)5.01(s，2H)7.46(t，1H)7.56(d，1H)7.62(d，2H)7.99(d，1H)8.10(s，1H)8.70(d，2H0。

[0938] The following compounds were prepared in analogy to example 815:

example No. 2	Name (R)	1HNMR	MS
example No. 2	Name (R)	1HNMR	MS	816	8- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethyl]-3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4]Triazole [4, 3-a ]]Pyrimidines
817	8- [5- (3-fluoro-phenyl) - [1, 3, 4]]Oxadiazol-2-ylmethyl]-3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4]Triazole [4, 3-a ]]Pyrimidines			816
817				818	8- {1- [5- (3-chloro-phenyl) - [1, 3, 4] ]Oxadiazol-2-yl]-ethyl } -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4]Triazole [4, 3-a ]]Pyrimidines	1.81(d，3H)2.19(m，2H)3.47(m，2H)4.12(m，2H)6.07(q，1H)7.42(m，1H)7.49(m，1H)7.61(m，2H)7.91(m，1H)8.00(m，1H)8.70(m，2H)
819	8- [5- (5-chloro-2-fluorophenyl) - [1, 2, 4]]Oxadiazol-3-ylmethyl]-3-furan-2-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4]Triazole [4, 3-a ]]Pyrimidines	2.23(m，2H)3.50(m，2H)4.20(m，2H)4.97(s，2H)6.49(m，1H)6.89(d，1H)7.19(t，1H)7.48(m，1H)7.51/m，1H)8.06(m，1H)		818

820

8- {1- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-yl]-ethyl } -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4]Triazole [4, 3-a ]]Pyrimidines

1.74(d，3H)2.17(m，2H)3.45(m，2H)4.10(m，2H)5.96(m，1H)7.44(t，1H)7.53(m，1H)7.59(m，2H)7.97(m，1H)8.08(m，1H)8.67(d，2H)

[0939] Example 821

[0940]3- (4-Ethyl-5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) -5- (1H-pyrrol-3-yl) - [1, 2, 4] oxadiazole

[0941]3-chloromethyl-5- [1- (toluene-4-sulfonyl) -1H-pyrrol-3-yl]-[1，2，4]Oxadiazole (50mg) and potassium hydroxide (50mg) were heated in methanol (5ml) for 2 h. The mixture was diluted with ethyl acetate (10ml), washed with water and brine, and then MgSO₄Dried, filtered and concentrated. Using fast silica gel chromatography with 40% of ethylEthyl acetate in heptane was isolated in 57% yield to give the title compound.¹H NMR(CDCl₃)δ(ppm)：9.8(s，1H)，7.5(m，2H)，7.4(d，1H)，7.2(dd，1H)，6.8(m，1H)，6.7(d，1H)，4.5(s，2H)，4.1(q，2H)，1.4(t，3H)。

[0942] Example 822

[0943]4- {5- [5- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-3-ylmethylsulfanyl ] -4-methyl-4H- [1, 2, 4] triazol-3-yl } -pyridine 1-oxide

[0944]Mixing 4- {5- [5- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethylthio]-4-methyl-4H- [1, 2, 4 ]Triazol-3-yl } -pyridine and wet 57% -86% MCPBA (52.4mg, 0.20-0.30mmol) were dissolved in dichloromethane (4ml) and stirred for 16 h. The reaction mixture was purified by reverse phase preparative LC to give the title compound (7.5mg, 8%).¹HNMR(CDCl₃)，δ(ppm)：8.33(d，2H)，8.06(m，1H)，7.96(m，1H)，7.67(d，2H)，7.57(m，1H()，7.46(apparentt，1H)，4.60(s，2H)，3.71(s，3H)。

[0945] Example 823

[0946]5- (3-chloro-phenyl) -3- (2-furan-2-yl-3-methyl-3H-imidazole 4-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0947]2-Furan-2-yl-3-methyl-3, 5-dihydro-imidazol-4-one (described in Takeuchi, H., Hagiwara, S., Eguchi, S., Tetrahedron (1989) 6375-one 6386) (50mg, 0.30mmol) was dissolved in dioxane (3ml) and Lawesson's reagent (136mg, 0.34mmol) was added. The reaction mixture was heated to reflux overnight and then brought to room temperature at which time DIPEA (212ml, 1.22mmol) and 3-chloromethyl-5- (3-chloro-phenyl) - [1, 2, 4] were added]Oxadiazole (140mg, 0.61 mmol). The resulting mixture was heated to reflux for 5 hours and then kept at room temperature overnight. Ethyl acetate was added and the reaction mixture was washed with water and then brine. With MgSO₄The organic phase was dried and evaporated. Flash chromatography using a chloroform solution containing 1% methanol gave the title compound (13mg, 11%).¹H NMR(CD₃OD)δ(ppm)：7.96(m，1H)，7.90(m，1H)，7.60(dd，1H)，7.57(ddd，1H)，7.46(t，1H)，7.09(s，1H)，6.86(dd，1H)，6.52(dd，1H)，3.95(s，2H)，3.74(s，3H)。

[0948] Example 824

[0949]5- (5-chloro-2-fluoro-phenyl) -3- [4- (2-fluoro-ethyl) -5-thiophen-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl ] - [1, 2, 4] oxadiazole

[0950]To 2- {3- [5- (5-chloro-2-fluoro-phenyl) - [1, 2, 4%]Oxadiazol-3-ylmethylthio]-5-thiophen-2-yl- [1, 2, 4]Add DAST (32mL, 0.24mmol) dropwise to a cooled solution (-15 deg.C) of triazol-4-yl } -ethanol (46mg, 0.11mmol) in dry THF (15 mL). The mixture was stirred at room temperature for 1.5 h, then quenched with MeOH (1 ml). The solvent was removed under reduced pressure and the residue partitioned between brine and EtOAc. The aqueous layer was extracted with EtOAc (2 × 20 ml). The combined organic layers were washed with brine (10ml) and dried (MgSO)₄) And concentrated under reduced pressure. Purification by flash chromatography (EtOAc: heptane 2: 1) and preparative HPLC afforded the title compound as a white solid (11mg, 22%).¹H NMR(CDCl₃)δ(ppm)：8.05(dd，1H)，7.52(m，3H)，7.20(m，1H)，7.16(m，1H)，4.75(t，1H)，4.63(m，3H)，4.45(m，2H)。

[0951] Example 825

[0952]5- (5-chloro-thiophen-3-yl) -3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylsulfanylmethyl) - [1, 2, 4] oxadiazole

[0953]According to the preparation of 2- [5- (3-methoxy-phenyl) - [1, 2, 4]]Oxadiazol-3-ylmethylthio]Process for the preparation of (E) -1H-phenylimidazole starting from 1- [5- (5-chloro-thiophen-3-yl) - [1, 2, 4] with the exception of using a molar equivalent of cesium carbonate instead of potassium carbonate as base]Oxadiazol-3-ylmethoxy radical]-1H-benzotriazole (32.3mg, 0.097mmol) and 4-ethyl-5-furan-2-yl-2, 4-dihydro- [1, 2, 4-dihydro- [ 2]Triazole-3-thione (23mg) the title compound was prepared using 50% EtOAc in n-heptane as the chromatographic eluent to give 21 mg. ¹H NMR(CDCl₃)δ(ppm)：7.95(d，1H)，7.57(dd，1H)，7.44(d，1H)，7.07(dd，1H)，6.56(dd，1H)，4.56(s，2H)，4.22(q，2H)，1.35(t，3H)。

[0954] Example 826

[0955]3- [3- (4-Ethyl-5-furan-2-yl-4H- [1, 2, 4] triazol-3-ylthiomethyl) - [1, 2, 4] oxadiazol-5-yl ] -4-hydroxy-benzonitrile

[0956]Using Rogers et al, Tetrahedron Letters (2002) 43: 3585-3587 by general methods. To 3- [3- (4-ethyl-5-furan-2-yl-4H- [1, 2, 4] at 0 DEG C]Triazol-3-ylthiomethyl) - [1, 2, 4]Oxadiazol-5-yl]A stirred solution of-4-fluoro-benzonitrile (20mg, 0.050mmol), 2- (methylsulfonyl-ethanol) (9.38mg, 0.075mmol) and DMF (0.05M) was added NaH (5.8mg, 0.150 mmol). Stir for 20 min and remove the ice bath. Stir for an additional 20 minutes and warm to room temperature. The reaction mixture was quenched with 1N HCl solution and partitioned between ethyl acetate and brine. Drying the organic layer (Na)₂SO₄) Filtered and concentrated to dryness. The crude organic was purified by flash chromatography using ethyl acetate followed by a solution of 5% methanol in ethyl acetate to give the title compound (8.1mg, 41%, white solid).¹H NMR(CDCl₃)，δ(ppm)：8.25(m，1H)，7.75(m，1H)，7.60(s，1H)，7.18(m，2H)，6.60(m，1H)，4.64(s，2H)，4.25(q，2H)，1.38(t，3H)。

[0957] Example 827

[0958]3- [ 4-methyl-5- (methylsulfonyl) -4H-1, 2, 4-triazol-3-yl ] pyridine

[0959]

[0960]KMnO4(5g, 32mmol) was added to 3- [ 4-methyl-5- (methylthio) -4H-1, 2, 4-triazol-3-yl]Pyridine (6.0g, 29mmol) in H ₂O (40mL) and acetic acid (100 mL). After stirring at room temperature for 1 hour, NaOH solution (4M) was added to alkalify the reaction. Adding CHCl₃And passing through diatomiteThe mixture was filtered. The layers were separated and the aqueous phase was washed with CHCl₃And (6) washing. The combined organic phases were dried and concentrated to yield 3.67g (53%) of the title compound.¹H NMR：3.59(s，3H)3.99(s，3H)7.52(m，1H)8.02(dt，1H)8.83(dd，IH)8.91(m，1H)

[0961] The following compounds are prepared in analogy to 3- [ 4-methyl-5- (methylsulfonyl) -4H-1, 2, 4-triazol-3-yl ] pyridine:

[0962] example 831

[0963] 4-methyl-3- (methylsulfonyl) -5- (trifluoromethyl) -4H-1, 2, 4-triazole

[0964]

[0965]To a solution of 4-methyl-3- (methylthio) -5- (trifluoromethyl) -4H-1, 2, 4-triazole (4.15g, 21.0mmol) in DCM (150ml) was added mCPBA (57-86%, 15.1g, 52.6mmol) in portions at 0 ℃. After stirring overnight at room temperature, DCM (150ml) was added. With NaHCO₃Saturated solution, Na₂S₂O₃The resulting mixture was washed with saturated solution and brine, dried and evaporated to give 4.4g (91%) of the title compound. MS (M)⁺-1)＝228。

[0966] The following compounds were prepared in analogy to 4-methyl-3- (methylsulfonyl) -5- (trifluoromethyl) -4H-1, 2, 4-triazole:

[0967] preparation of intermediate compounds

[0968] Example 834

[0969]3- [ 4-methyl-5- (methylthio) -4H-1, 2, 4-triazol-3-yl ] pyridine

[0970]

[0971]MeI (2mL, 32mmol) in EtOH (10mL) was added to a mixture of 4-methyl-5-pyridin-3-yl-2, 4-dihydro-3H-1, 2, 4-triazole-3-thione in 1M NaOH (70mL, 70 mmol). After stirring at room temperature for 1 hour, DCM was added and the layers were separated. The aqueous phase was washed with DCM and the combined organic layers were dried and concentrated to give 6.5g (98%) of the title compound.¹H NMR：2.76(s，3H)3.59(s，3H)7.43(m，1H)7.99(m，1H)8.71(m，1H)8.86(m，1H)

[0972] According to the reaction with 3- [ 4-methyl-5- (methylthio) -4H-1, 2, 4-triazol-3-yl ] pyridine

The following compounds were prepared in a similar manner:

[0973] example 839

[0974] 4-methyl-3- (methylthio) -5- (trifluoromethyl) -4H-1, 2, 4-triazole

[0976]4-Methylaminothiourea (10.0g, 95.09mmol) in TFA (46.7ml) was heated to reflux overnight. Excess TFA was removed by evaporation. The residue was dissolved in 1M NaOH (100ml)After the aqueous solution, CH in EtOH (22ml) was added dropwise₃I (4.47ml, 71.17 mmol). The resulting mixture was stirred overnight. Crystallization was induced by partial evaporation of the solvent. By H₂After dilution, the solid was collected by filtration and dried to give the title compound (5.2g, 28%). MS (M)⁺+1)198

[0977] Example 840

[0978]3- (3, 5-difluorophenyl) -4-methyl-5- (methylthio) -4H-1, 2, 4-triazole

[0979]

[0980]The title compound was obtained as a by-product of the synthesis of 5- (3, 5-difluorophenyl) -N, 4-dimethyl-4H-1, 2, 4-triazol-3-amine. ¹HNMR(DMSO-D6)：2.66(s，3H)3.60(s，3H)7.43-7.52(m，3H).MS(M⁺+1)242。

[0981] Example 841

[0982] 4-methyl-5-pyridin-3-yl-2, 4-dihydro-3H-1, 2, 4-triazole-3-thione

[0983]

[0984]Nicotinyl hydrazide (10g, 73mmol) and methyl isothiocyanate (5.6g, 76mmol) were mixed in 2-propanol (150ml) and heated at 70 ℃ overnight. The reaction was cooled to room temperature and evaporated to dryness. H is to be₂O (180mL) and NaHCO₃(12.8g, 152mmol) was added to the residue and the mixture refluxed overnight. The reaction mixture was cooled to room temperature and acidified with concentrated hydrochloric acid, and the title compound was collected by filtration to give 13.1g (93%), LC-MS (M)⁺+1)：193

[0985] According to the reaction with 4-methyl-5-pyridin-3-yl 2, 4-dihydro-3H-1, 2, 4-triazole 3-thione

The following compounds were prepared in a similar manner:

[0986] example 844

[0987]5- (4-fluorophenyl) -4-methyl-2, 4-dihydro-3H-1, 2, 4-triazole-3-thione

[0988]

[0989]To a solution of 4-methylaminothiourea (4.24g, 40.30mmol) in pyridine (50ml) was added 4-fluorobenzoyl chloride (4.9ml, 40.00mmol) dropwise, and the resulting mixture was stirred at room temperature overnight. Pyridine was removed by evaporation and the residue was taken up in saturated NaHCO₃The aqueous solution was heated at reflux overnight. After cooling to room temperature, the product was collected by filtration, washed with water and dried in vacuo to give 3.22g (38%), which was used in the next step without further purification.¹HNMR：3.9(m，3H)6.98(t，2H)7.92(m，2H)。

[0990] Example 845

[0991] N' - [ (3-chlorobenzoyl) oxy ] 2-hydroxypropanimidamide

[0992]

[0993]6.45g of crude N', 2-dihydroxypropaneimineamide are cooled on an ice bath with 23.5mL of DEA in TBDF (200 mL). To the slurry was added 21.94g of 3-chlorobenzoyl chloride. The mixture was warmed to room temperature and stirred for 2 h. Et was added₂O (200mL), saturated withNH₄After washing with aqueous Cl, the aqueous layer was re-extracted, the organic layers were combined and concentrated and dried under vacuum to give 27.24g of the crude title compound which was used directly in the next step 1- [5- (3-chlorophenyl) - [1, 2, 4]]Oxadiazol-3-yl]And (3) ethanol. LC-MS (M)⁺+1)：243

[0994] Example 846

[0995] 3-chloro-N' - { [ (2R) -2-hydroxypropionyl ] oxy } benzamidine

[0996]

[0997]3.82g (22.4mmol) of 3-chloro-N' -hydroxybenzamidine and 2.00g (22.2mmol) of (R) -lactic acid were dissolved in DCM (5OmL) and DMF (15mL) at 0 ℃ under argon. After 5 min 3.4mL (33.2mmol) DIC and 3.50g (25.9mmol) HOBt were added. After 15 minutes the mixture was warmed to room temperature and stirred for a further 3 hours, then filtered and washed with DCM. The filtrate was dried in vacuo to near dryness, treated with EA, and treated with NaHCO₃The aqueous solution was then washed with water and finally with 2M aqueous citric acid. Na for EA layer₂SO₄And the mixture of silica is filtered. The oil was obtained by flash chromatography (Hep/EA ═ 4/1 to 2/1 to 1/2) and treated with Et ₂Trituration and drying afforded 4g (75%) of the title compound.¹HNMR：7.69(t，1H)，7.55-7.59(m，1H)，7.44-7.49(m，1H)，7.36(t，1H)，5.10(s，2H)，4.50(q，1H)，1.54(d，3H)

[0998] Example 847

[0999] N', 2-dihydroxypropane imine amides

[1000]

[1001]44.2g (0.64mol) of hydroxylamine hydrochloride at room temperatureAnd 25.5g (0.64mol) of sodium hydroxide were dissolved in ethanol (500mL) and stirred for 3 hours. After filtration, 8.11g (0.11mol) of 2-hydroxypropionitrile was added to the filtrate, and the mixture was stirred for another 4 hours. Concentration to dryness gave the title compound which was used directly in the next step.¹HNMR(DMSO-D6)：8.88(s，1H)，5.15(s，1H)，5.02(s，1H)，4.00(q，1H)，1.19(d，3H)。

[1002] Example 848

[1003]1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] -N-methylmethanamine

[1004]

[1005]Reacting MeNH₂A solution in EtOH (6mL, 8M, 48mmol) was added to a solution of 3- (chloromethyl) -5- (3-chlorophenyl) -1, 2, 4-oxadiazole (1.5g, 6.5mmol) in EtOH (20 mL). After 20 hours, the solvent was evaporated off and the residue was dried in vacuo to yield 1.47g (100%) of the title compound. LC-MS (M)⁺+1)：224

[1006] According to the formula with 1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] -N-methylmethanamine

The following compounds were prepared in a similar manner:

[1007] example 856

[1008] N- { [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol 3-yl ] methyl } -N' -cyclopropyl-N-methylthiourea

[1009]

[1010]Cyclopropyl isothiocyanate (650mg, 6.6mmol) was added to 1- [5- (3-chlorophenyl) - [1, 2, 4]]Oxadiazol-3-yl ]-N-methyl methylamine (1.47g, 6.5mmol) in EtOH (20 mL). After 3 hours, the precipitate formed was filtered and washed with cold EtOH to yield 1.63g (78%) of the title compound. LC-MS (M)⁺+1)：323。

[1011] The following compounds are prepared in analogy to N- { [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] methyl } -N' -cyclopropyl-N-methylthiourea:

[1012] example 864

[1013]1- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-ylmethyl ] -3-cyclopropyl-1-methyl-thiourea

[1014]

[1015]3- (3-chloro-phenyl) - [1, 2, 4] at room temperature]Oxadiazol-5-ylmethyl]-methyl-amine (415mg, 1.85mmol) was mixed with cyclopropyl isothiocyanate (220mg, 2.22mmol) in chloroform (5mL) for 2 hours. The reaction mixture was concentrated and Et₂The residue was triturated to give the title compound (406mg, 67.9%).¹H-NMR：8.09(s，1H)，7.98(d，1H)，7.51(d，1H)，7.46(t，1H)，6.00(w，1H)，5.53(s，2H)，3.28(s，3H)，3.11(m，1H)，2.45(s，3H)5 0.94(m, 2H) and 0.69(m, 2H).

[1016] Example 865

[1017] N- { [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] methyl } -N' -cyclopropyl-N-methyliminothiocarbamic acid methyl ester

[1018]

[1019]MeI (320. mu.L, 5.1mmol) and N- { [5- (3-chlorophenyl) - [1, 2, 4] were mixed in EtOH (20mL)]Oxadiazol-3-yl]Methyl } -N' -cyclopropyl-N-methylthiourea (1.59g, 4.9mmol) and heated at 70 ℃ for 2 hours. The reaction was cooled to room temperature and NaOH (1M) was added to pH 10. EA was added and the mixture was stirred for 5 minutes. The layers were separated and the aqueous phase was extracted with EA. The organic phase was dried and concentrated. The product is purified by column chromatography (Hep-EA 1: 1) to yield 960mg (59%) of the title compound. LC-MS (M) ⁺+1)：337

[1020] The following compounds are prepared analogously to methyl N- { [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] methyl } -N' -cyclopropyl-N-methyliminothiocarbamate:

[1021] example 872

[1022]1- {1- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -ethyl } -1-cyclopropyl-2-ethyl-3-methyl-isothiourea

[1023]

[1024]1- {1- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]-Ethyl } -1-cyclopropyl-3-methyl-thiourea (287mg, 0.85mmol) was mixed with a solution of iodoethane (484mg, 3.4mmol) in MeOH (5mL) at 60 ℃ overnight. The reaction mixture was concentrated and basified with saturated sodium carbonate and then extracted with DCM. The organic phase was dried and concentrated to give the title compound (298mg, 96%).¹H-NMR：8.11(s，1H)，8.01(d，1H)，7.51(d，1H)，7.46(t，1H)，5.51(m，1H)，3.27(s，3H)，2.85-3.00(m，2H)，2.60(m，1H)，1.79(d，3H)3 1.30(t，3H)，0.83(m)

[1025] Example 873

[1026]1- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-ylmethyl ] -2-ethyl-1-isopropyl-3-methyl-isothiourea

[1027]

[1028]According to the formula of 1- {1- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]The title compound is prepared in analogy to-ethyl } -1-cyclopropyl-2-ethyl-3-methyl-isothiourea.¹H-NMR: 8.09(s, 1H), 7.97(d, 1H), 7.50(d, 1H), 7.44(t, 1H), 4.87(m, 1H), 4.66(s, 2H), 3.15(s, 3H), 2.88(q, 2H), 1.35(t, 3H) and 1.23(s, 6H)

[1029] Example 874

[1030] N-cyclopropyl-N' -methyl imine thiocarbamic acid methyl ester hydroiodide

[1031]

[1032] MeI (265ml, 4.2mmol) was added to a solution of N-cyclopropyl-N' -methylthiourea (500mg, 3.8mmol) in acetone (10ml), and the mixture was heated to reflux. After stirring for 20 min, the heating was stopped and the solvent was removed under reduced pressure to give 960mg of crude title compound which was used directly in the next step.

[1033] Example 875

[1034] N-cyclopropyl-N' -methylhydrazone (carbohydrazonic) diamide hydroiodide salt

[1035]

[1036] Crude methyl N-cyclopropyl-N' -methyliminothiocarbamate hydroiodiate (960mg, 3.5mmol) was mixed with a solution of hydrazine hydrate (240ml, 3.9mmol) in ethanol and heated at reflux for 3 hours. The mixture was kept at 7 ℃ for 12 hours to give the crude title compound (0.9g), which was used directly in the next step.

[1037] Example 876

[1038]5- (3, 5-difluorophenyl) -N, 4-dimethyl-4H-1, 2, 4-triazol-3-amine

[1039]

[1040]To a solution of methyl N, N' -dimethyliminecarbamate hydroiodide (5.0g, 20.3mmol) in pyridine (30ml) was added 3, 5-difluorobenzoyl hydrazine (3.5g, 20.3mmol) and the mixture was heated at reflux for 24 h. After cooling to room temperature, the reaction mixture was poured into ice/H ₂O, the precipitate formed was removed by filtration. With CHCl₃The filtrate was extracted, dried and the organic phase concentrated. With Et₂The residue was washed with O and then CHCl₃The MeOH solution is purified by column chromatography from 99: 1 to 10: 1. Together with 3- (3, 5-difluorophenyl) -4-methyl-5- (methylthio) -4H-1, 2, 4-triazole (0.44g, 9%) as a by-product gave the title compound (0.83g, 18%).¹H NMR(DMSO-D6)：2.83(d，3H)3.41(s，3H)6.20(d，1H)7.35(m，3H)，MS(M⁺+1)225。

[1041] Example 877

[1042] Methyl- (4-methyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -amine

[1043]

[1044]A mixture of 1000mg (4.35mmol) N-amino-N', N "-dimethyl-guanidinium hydroiodide (Henry; Smith; J.Amer.chem.Soc; 73; 1951; 1858) and 774mg (4.35mmol) isonicotinoyl chloride hydrochloride in pyridine (3mL) was heated under microwave radiation at 160 ℃ for 5 minutes. Adding saturated K₂CO₃Aqueous solution of CHCl₃The mixture is extracted. The organic phase was dried and concentrated. Recrystallization from EtOH, water and EA gave 216mg (26%) of the title compound.¹HNMR(DMSO-d6)：2.85(d，3H)3.45(s，3H)6.25(d，1H)7.65(m，2H)8.67(m，2H)。

[1045] Example 878

[1046] 3-pyridin-4-yl-5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrimidine

[1047]

[1048]A solution of 750mg (3.1mmol), (1, 4, 5, 6-tetrahydro-pyrimidin-2-yl) -hydrazinium hydroiodide (Krezel, IZabella; Pharmazie; 1994; p.27-31) and 552mg (3.1mmol) of isonicotinoyl chloride hydrochloride in 3ml pyridine is heated at 120 ℃ overnight. The reaction mixture was cooled and saturated with K ₂CO₃The aqueous solution was diluted and extracted with chloroform. The combined organic extracts were dried and concentrated. Flash chromatography (DCM/MeOH 10: 1) afforded 83mg (18%) of the title compoundThe title compound.¹H NMR：1.91(m，2H)3.24(m，2H)4.13(m，2H)7.67(m，2H)8.65(m，2H)

[1049] Example 879

[1050] N, 4-dimethyl-5-pyridin-3-yl-4H-1, 2, 4-triazol-3-amine

[1051]

[1052]N-amino-N', N "-dimethyl-guanidine (500mg, 2.17mmol) [ j.amer.chem.soc; 1951, providing a feed additive; page 1858]And a mixture of nicotinoyl chloride hydrochloride (385mg, 2.17mmol) in pyridine (10mL) was refluxed overnight. Adding saturated K₂CO₃Combined use of CHCl in aqueous solution₃The mixture is extracted. The organic phase was dried and concentrated. The crude product, 240mg (61%), was used in the next step without further purification. LC-MS (M)⁺+1)：190

[1053] Example 880

[1054] N-cyclopropyl-4-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine

[1055]

[1056]Isonicotinoyl chloride hydrobromide (630mg, 3.5mmol) was added to a mixture of N-cyclopropyl-N' -methylhydrazone diamide hydroiodide (900mg, 3.5mmol) in pyridine (10ml) and the mixture was stirred at room temperature for 2 hours. The mixture was heated at 160 ℃ for 10 minutes under microwave irradiation. Water (50ml) was added and the mixture was extracted with DCM. The combined organic phases were dried and concentrated to give the desired product using preparative HPLC. LCMS (M)⁺+1)216

[1057] Example 881

[1058]5- (2-methoxypyridin-4-yl) -N, 4-dimethyl-4H-1, 2, 4-triazol-3-amine

[1059]

[1060]2-Chloroisoinicotinic acid (2.2g, 13.8mmol) was refluxed in thionyl chloride (50ml) for 5 hours. The solvent was evaporated (co-evaporated with toluene), the residue dissolved in pyridine (25ml), which was added portionwise to N, N' -dimethylhydrazone diamide hydroiodide (3.0g, 13.0mmol) dissolved in pyridine (25 ml). The reaction mixture was heated at 120 ℃ overnight and the solvent was evaporated, followed by addition of water (10ml) and filtration. The remaining aqueous solution was purified by preparative HPLC to give 0.54g (19%) of intermediate 5- (2-chloropyridin-4-yl) -N, 4-dimethyl-4H-1, 2, 4-triazol-3-amine.¹H-NMR (DMSO-d 6): 8.51(dd, 1H), 7.76(m, 1H), 7.71(dd, 1H), 6.37(m, 1H), 3.49(s, 3H), 2.86(d, 3H). This intermediate (0.52g, 2.3mmol) was dissolved in MeOH (35ml) and sodium methoxide (4.4ml of 30% MeOH solution, 23.3mmol) was added. The mixture was refluxed overnight, brine was added and CHCl was used₃And (4) extracting. Drying (MgSO)₄) And the combined organic phases were concentrated to give the title compound (0.28g, 55%).¹H NMR(DMSO-d6)：8.26(d，1H)，7.27(dd，1H)，7.05(m，1H)，6.26(q，1H)，3.90(s，3H)，3.44(s，3H)，2.85(d，3H)。

[1061] Example 882

[1062]4- (4-cyclopropyl-5-methyl-4H-1, 2, 4-triazol-3-yl) pyridine

[1063]

[1064]Oxalyl chloride (860ml, 10mmol) was slowly added to N-cyclopropylacetamide (1g, 10mmol) [ Bouzoubaa, Mohamed, j.med.chem.; 28; 7; 1985; 896-900 ]And (2) a step of adding a compound of,6-lutidine (2.33ml, 20mmol) in DCM (30 ml). After stirring for 30 min, isonicotinyl hydrazide (1.37g, 10mmol) was added. The mixture was stirred at room temperature for 3 hours. The solvent was then removed under reduced pressure. Saturated aqueous sodium carbonate (15ml) was added and the mixture was heated at reflux for 2 hours and then extracted with EA. The combined organic phases were dried and concentrated. The resulting solid was recrystallized from EA to give the title compound (1.1 g).¹H NMR：0.7(m，2H)1.2(m，2H)2.6(s，3H)3.3(ddd，1H)7.7(m，2H)8.7(d，2H)

[1065] The following compounds are prepared according to the formula analogous to 4- (4-cyclopropyl-5-methyl-4H-1, 2, 4-triazol-3-yl) pyridine:

[1066] example 885

[1067]3- [ 3-cyclopropyl-2- (2, 6-dichloro-pyridin-4-yl) -3H-imidazol-4-yl ] -2-methyl-acrylic acid ethyl ester

[1068]

[1069]3-cyclopropyl-2- (2, 6-dichloro-pyridin-4-yl) -3H-imidazole-4-carbaldehyde (1.48g, 5.25mmol), triethyl-2-phosphopropyl ester (1.46ml, 6.83mmol), and DBU (1.02ml, 6.83mmol) were dissolved in acetonitrile (20 ml). After stirring at 78 ℃ overnight, the reaction mixture was cooled to room temperature, diluted with water and extracted with DCM. Drying (Na)₂SO₄) The combined organic phases were filtered and concentrated in vacuo. The crude product was purified on silica gel using 6% EA in DCM and the isolated residue triturated with hexane to isolate the title compound (1.66g, 86%). ¹H-NMR：7.86(m，1H)，7.75(d，2H)，7.43(s，1H)，4.34(q，2H)，3.45(m，1H)，2.19(s，3H)，1.39(t，3H)，1.29(m，2H)，0.78(m，2H)。

[1070] Example 886

[1071]3- [ 3-cyclopropyl-2- (4-methoxy-phenyl) -3H-imidazol-4-yl ] -acrylic acid ethyl ester

[1072]

[1073]3-cyclopropyl-2- (4-methoxy-phenyl) -3H-imidazole-4-carbaldehyde (500mg, 2.06mmol), triethylphosphoacetate (0.53ml, 2.68mmol) and DBU (0.40ml, 2.68mmol) were dissolved in acetonitrile (5 ml). After stirring at 78 ℃ overnight, the reaction mixture was cooled to room temperature, diluted with water (50ml) and extracted with DCM. Drying (Na)₂SO₄) The combined organic phases were filtered and concentrated in vacuo. Purification on silica gel using 50% hexane afforded the title compound (471mg, 73%).¹H-NMR：7.85(d，1H)，7.79(d，2H)，7.49(s，1H)，7.00(d，2H)，6.36(d，1H)，4.31(q，2H)，3.89(s，3H)，3.39(m，1H)，1.36(t，3H)，1.14(m，2H)，0.69(m，2H)。

10741 example 887

[1075]3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -2-methyl-acrylic acid ethyl ester

[1076]

[1077]At room temperature, (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4-]Triazol-3-yl) -methanol (6.8g, 31.4mmol) with MnO₂(40g, 0.46mol) were mixed in acetonitrile for 2 hours and then heated at 80 ℃ for another 30 minutes. The reaction mixture was filtered through celite. The filtrate was mixed with ethyl 2- (diethoxy-phosphoryl) -propionate (12.35g, 51.8mmol) and DBU (7.17g, 47mmol) at 80-90 ℃ for 4 h. The reaction mixture was concentrated and dissolved in EAAnd rinsing with water and saline. The organic phase was dried, concentrated and triturated with hexane to give the title compound 5.76g (61%). ¹H-NMR: 8.78(d, 2H), 7.78(d, 2H), 7.67(s, 1H), 4.32(q, 2H), 3.43(m, 1H), 2.53(s, 3H), 1.38(t, 3H), 1.24(m, 2H) and 0.73(m, 2H).

[10781 example 888

[1079]3- [ 3-cyclopropyl-2- (4-methoxy-phenyl) -3H-imidazol-4-yl ] -2-methyl-propionic acid ethyl ester

[1080]

[1081]3-cyclopropyl-2- (4-methoxy-phenyl) -3H-imidazole-4-carbaldehyde (475mg, 1.96mmol), triethyl-2-phosphopropionate (0.63ml, 2.94mmol) and DBU (0.44ml, 2.94mmol) were dissolved in acetonitrile (5 ml). After stirring at 78 ℃ overnight, the reaction mixture was cooled to room temperature, diluted with water (50ml) and extracted with DCM. Drying (Na)₂SO₄) The combined organic phases were filtered and concentrated in vacuo to give 3- [ 3-cyclopropyl-2- (4-methoxy-phenyl) -3H-imidazol-4-yl]-2-methyl-acrylic acid ethyl ester, dissolved in ethanol and hydrogenated over 10% Pd/C (0.5g) at normal pressure for 24 hours. The reaction mixture was filtered through a pad of celite and concentrated. After purification on silica gel (EA/DCM ═ 1/1), the isolated product was dissolved in Et₂O (10ml) combined with HCl (in Et)₂1N in O, 4 ml). The resulting mixture was concentrated and Et₂The residue was triturated and the title compound isolated as a solid (466 mg).¹H-NMR：7.90(d，2H)，7.10(m，3H)，4.16(m，2H)，3.90(s，3H)，3.47(m，1H)，3.24(m，1H)，2.85(m，2H)，1.37(d，3H)，1.27(m，5H)，0.75(m，2H)。

[1082]Example 889

[1083]3- [2- (4-methoxy-phenyl) -3-methyl-3H-imidazol-4-yl ] -2-methyl-propionic acid ethyl ester

[1084]

[1085]According to the formula with 3- [ 3-cyclopropyl-2- (4-methoxy-phenyl) -3H-imidazol-4-yl]The title compound was prepared analogously to 2-methyl-propionic acid ethyl ester.¹H-NMR：7.52(dd，2H)，6.99(dd，2H)，6.88(s，1H)，4.15(q，2H)，3.87(s，3H)，3.59(s，3H)3.00(m，1H)，2.80(m，1H)，2.67(m，1H)，1.27(m，6H)。

[1086]Example 890

[1087]3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -2-methyl-propionic acid ethyl ester

[1088]

[1089]3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4)]Triazol-3-yl) -2-methyl-acrylic acid ethyl ester (5.76g, 19.3mmol) was hydrogenated with 10% Pd/C (3.0g) in EtOH (100ml) overnight. The reaction mixture was filtered and concentrated. The residue was triturated with hexane to give the title compound 3.1g (53%).¹H-NMR: 8.76(d, 2H), 7.73(d, 2H), 4.14(m, 2H), 3.35(m, 3H), 2.88(q, 1H), 1.39(d, 3H), 1.25(t, 3H), 1.18(m, 2H) and 0.73(m, 2H).

[1090] The following examples are prepared in analogy to 3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -2-methyl-propionic acid ethyl ester:

[1091] example 893

[1092]3- (3-cyclopropyl-2-pyridin-4-yl-3H-imidazol-4-yl) -2-methyl-propionic acid

[1093]

[1094]3- (3-cyclopropyl-2-pyridin-4-yl-3H-imidazol-4-yl) -2-methyl-propionic acid ethyl ester (1.02g, 3.40mmol) was combined with MeOH (8ml) and sodium hydroxide (1N in water, 5.1ml, 5.10 mmol). The mixture was stirred at room temperature for 5 hours and then concentrated in vacuo. The separated residue was treated with aqueous HCl (2N, 6ml) to isolate the title compound (702mg, 76%). ¹H-NMR(DMSO-d6)：8.63(dd，2H)，7.74(dd，2H)，6.82(s，1H)，3.55(m，1H)，3.09(m，1H)，2.82(m，2H)，1.19(d，3H)，1.08(m，2H)，0.56(m，2H)。

[1095] Example 894

[1096]3- [2- (4-methoxy-phenyl) -3-methyl-3H-imidazol-4-yl ] -2-methyl-propionic acid

[1097]

[1098]The title compound was synthesized in analogy to 3- (3-cyclopropyl-2-pyridin-4-yl-3H-imidazol-4-yl) -2-methyl-propionic acid.¹H-NMR(DMSO-d6)：7.52(d，2H)，7.02(d，2H)，6.71(s，1H)，3.80(s，3H)，3.55(s，3H)2.89(m，1H)，2.67(m，2H)，1.15(d，3H)。

[1099] Example 895

[1100] 3-cyclopropyl-2- (4-methoxy-phenyl) -3H-imidazole-4-carbaldehyde

[1101]

[1102]N-cyclopropyl-4-methoxy-benzamidine (0.90g, 4.75mmol), 2-bromo-3-isopropoxy-propenal (1.37g, 7.12mmol) and K₂CO₃(0.98g, 7.12mmol) was mixed with chloroform (10ml) and water (1.2ml), followed by stirring at room temperature for 24 hours. The reaction mixture was dried (Na)₂SO₄) After this time, the filtrate was filtered and concentrated in vacuo, and the crude residue was purified by flash chromatography (40% EA in hexanes) to isolate the title compound (973mg, 85%).¹H-NMR：9.83(s，1％)，7.82(m，3H)，7.02(d，2H)，3.89(s，3H)，3.58(m，1H)，1.13(m，2H)，0.64(m，2H)。

[1103] The following example was prepared in analogy to 3-cyclopropyl 2- (4-methoxy-phenyl) -3H-imidazole-4-carbaldehyde:

[1104] example 898

[1105] (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4] triazol-3-yl) -methanol

[1106]

[1107]4- (4-cyclopropyl-4H- [1, 2, 4] in a sealed bottle]Triazol-3-yl) -pyridine (6.85g, 36.8mmol) and 37% formaldehyde (30mL) were mixed and heated at 135 deg.C overnight. The reaction mixture was concentrated on silica gel and then mixed with MeOH. The mixture was filtered and washed with MeOH. The filtrate was again concentrated on silica gel and loaded on flash column with 10% MeOH (2M NH) ₃) Was eluted with DCM to give the title compound (6.8 g)，85％)。¹H-NMR(DMSO-d6)：8.75(d，2H)，7.84(d，2H)，5.63(t，1H)，4.72(d，2H)，3.66(m，1H)，1.04(m，2H)，0.73(m，2H)。

[1108] Example 899

[1109] 3-chloro-N' -hydroxybenzeneimine amide (hydroxybenzenecarboximidamide)

[1110]

[1111]A solution of 3.35mL (30.0mmol) of 3-chlorobenzonitrile in ethanol (40mL) was added to a solution of 2.47g (35.5mmol) of hydroxylamine hydrochloride and 1.42g (35.5mmol) of NaOH in water (20mL) at room temperature, followed by heating at 90 ℃ for 24 hours. After cooling, the reaction mixture was concentrated and the residue was diluted with water, then filtered and dried to give 1.13g (93%) of the title compound.¹H NMR：8.11(s，1H)，7.72(s，1H)，7.61(m，1H)，7.46(m，1H)，7.36(m，1H)。

[1112] Example 900

[1113] N-cyclopropyl-4-methoxy-benzamidine

[1114]

[1115]4-methoxy-benzylidene ethyl ester hydrochloride (1.25g, 5.8mmol), DCM (5ml) and cyclopropylamine (0.92ml, 13.3mmol) were combined. After stirring at room temperature for 3 hours, the reaction mixture was concentrated in vacuo. The residue was treated with cold aqueous sodium hydroxide (1M) and extracted with EA. The combined organic phases were washed with water and brine and dried (Na)₂SO₄) Filtered and concentrated in vacuo to isolate the title compound (0.90g, 82%).¹H-NMR：7.64(d，2H)，6.90(d，2H)，5.3(bs，2H)，3.85(s，3H)，2.59(m，1H)，0.84(m，2H)，0.62(m，2H)。

[1116] Example 901

[1117] 4-methoxy-N-methyl-benzamidine

[1118]

[1119]Methylamine hydrochloride (2.28g, 33.8mmol) was suspended in toluene (16 ml). After cooling the resulting mixture to 0 ℃, trimethylaluminum (2M in toluene) was added dropwise under an argon atmosphere, and then the mixture was warmed to room temperature and stirred for 2 hours. To the mixture was then added a toluene (16ml) solution of 4-methoxybenzonitrile, followed by stirring at 80 ℃ for 24 hours. The mixture was cooled to room temperature and slowly poured onto CHCl on silica gel (10g) ₃(75ml) slurry. The slurry was stirred at room temperature for 15 minutes and filtered using MeOH. The filtrate was concentrated. The separated residue was dissolved in water (50ml) and taken up in CHCl₃And (4) extracting. The combined organic phases were washed with brine and dried (Na)₂SO₄) Filtered and concentrated in vacuo to isolate the title compound (1.25 g).¹H-NMR(DMSO-d6)：7.68(d，2H)，6.91(dd，2H)，6.33(br.s，2H)，3.77(s，3h)，2.77(s，3H)

[1120] Example 902

[1121]2, 6-dichloro-N-cyclopropyl-isonicotinamidine

[1122]

[1123]2, 6-dichloropyridine-4-carbonitrile (5g, 28.9mmol), methanol (50ml) and sodium methoxide (0.66ml, 2.89mmol) were combined and stirred at room temperature for 3 hours. A mixture of HCl in EtOH (24% w/w, 10mL) and cyclopropylamine (3mL, 43.4mmol) was added at 0 deg.C, followed by stirring at room temperature overnight. Concentrated under vacuumThe reaction mixture was condensed. The separated residue was treated with cold aqueous NaOH (1N, 75ml) and extracted with EA. The combined organic phases were washed successively with aqueous NaOH and brine and dried (Na)₂SO₄) Filtered and concentrated in vacuo. With Et₂The separated residue was O-purified to isolate the title compound (3.82 g).¹H-NMR：7.59(br.s，2H)，4.96(br.s，2H)，2.60(m，1H)，0.90(m，2H)，0.69(m，2H)。

[1124] Example 903

[1125] 4-methoxy-benzylidene amino acid ethyl ester hydrochloride

[1126]

[1127]4-methoxybenzonitrile and a 24% hydrochloric acid in EtOH were mixed at 0 ℃. The mixture was stirred at room temperature overnight and then concentrated in vacuo. With Et ₂The separated residue was triturated to isolate the title compound (1.25 g).¹H-NMR：12.3(br.s，1H)，11.6(br.s，1H)，8.43(d，2H)，7.04(d，2H)，4.91(t，3H)，3.90(s，3H)，1.61(t，3H)。

[1128] Example 904

[1129] 2-bromo-3-isopropoxy-propenal

[1130]

[1131]Under azeotropic conditions, a mixture of 2-bromomalondialdehyde, p-toluenesulfonic acid monohydrate, 2-propanol and cyclohexane was stirred at 86 ℃ in a flask equipped with a dean Stark trap. Further distillation removed an additional 40% of the original solvent volume. The mixture was cooled to 0 ℃ and then concentrated in vacuo to isolate the title compound (13.2 g).¹H-NMR：9.16(s，1H)，7.65(s，1H)，4.51(m，1H)，1.47(d，6H)。

[1132] Example 905

[1133]5- (3-chloro-phenyl) -isoxazole-3-carboxylic acid ethyl ester

[1134]

[1135]A solution of 4- (3-chloro-phenyl) -2, 4-dioxo-butyric acid ethyl ester (3.0g, 11.8mmol) and hydroxylamine hydrochloride (2.46g, 35.4mmol) in MeOH (60mL) was heated at 80 ℃ for 4 h. After cooling, the mixture was filtered and washed with cold MeOH to give the title compound (2.0g, 71%).¹H NMR：7.82(s，1H)，7.72(m，1H)，7.47(m，2H)，4.03(s，3H)。

[1136] Example 906

[1137]4- (4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine

[1138]

[1139]4-cyclopropyl-5-pyridin-4-yl-2, 4-dihydro-3H-1, 2, 4-triazole-3-thione (11.11g, 51mmol) was slowly added in wet Raney's (90g) in EtOH (200mL) in portions. The reaction mixture was heated at 60 ℃ for 3.5 hours and then filtered through celite. The filtrate was concentrated to give the title compound (6.85g, 72.3%). ¹H-NMR: 8.76(d, 2H), 8.71(s, 1H), 7.95(d, 2H), 3.75(m, 1H), 1.08(m, 2H) and 0.94(m, 2H).

[1140] Example 907

[1141] N-cyclopropyl propanamide

[1142]

[1143]A solution of propionic anhydride (6.41ml, 50.0mmol) and cyclopropylamine (3.48ml, 50.0mmol) in mesitylene (50ml) was heated to reflux for 6 h, then the solvent was evaporated off. Recrystallization from EA/hex gave the title compound (1.45g, 26%).¹H NMR：0.48(m，2H)0.76(m，2H)1.13(t，3H)2.14(q，2H)2.69(m，1H)

[1144] Example 908

[1145]4- (3-chloro-phenyl) -2, 4-dioxo-butyric acid ethyl ester

[1146]

[1147]Sodium hydride (60% oil dispersion, 1.24g, 31.1mmol) was added portionwise to a solution of 3-chloroacetophenone (4.0g, 25.9mmol) and diethyl oxalate (4.54g, 31.1mmol) in DMF (32mL) at 0 ℃. The mixture was stirred at room temperature for 1 hour and then heated at 80 ℃ for 0.5 hour. After cooling, the mixture was treated with 3n hcl and then diluted with EA. The organic layer was washed with water and saturated brine and dried (Na)₂SO₄) Filtration and concentration. The resulting residue was then purified by column chromatography using a hex solution containing 0-10% EA to give the title compound (4.43g, 67%).¹HNMR：15.12(br s，1H)，7.98(s，1H)，7.88(d，1H)，7.58(d，1H)，7.47(t，1H)，7.05(s，1H)，4.39(m，2H)，1.41(m，3H)。

[1148] Example 909

[1149]1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] ethanol

[1150]

[1151]27.2g of crude N' - [ (3-chlorobenzoyl) oxy]-2-hydroxypropanimidamide was dissolved in ethanol (250mL) and refluxed for 1 hour, followed by the addition of a solution of 14.0g (170mmol) of sodium acetate in water (40 mL). After refluxing overnight, cooling to room temperature, water (250ml) was added and the mixture was concentrated in vacuo to 1/2 which gave a precipitate which was filtered and recrystallized from EA/Hep to give 6.45g (25%) of the title compound. ¹H NMR： 8.14(s，1H)，8.02(d，1H)，7.57(d，1H)，7.47(t，1H)，5.04-5.14(m，1H)，2.51(d，1H)，1.67(d，3H)

[1152] Example 910

[1153]1- [5- (5-chloro-2-fluorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethanol

[1154]

[1155]According to the formula with 1- [5- (3-chlorophenyl) - [1, 2, 4]]Oxadiazol-3-yl]The title compound was prepared in a similar manner to ethanol.¹H-NMR：8.12(dd，1h)，7.49-7.58(m，1H)，7.18-7.27(m，1H)，5.12(q，1H)，1.68(d，3H)

[1156] Example 911

[1157]1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] propan-1-ol

[1158]

[1159]Propionaldehyde cyanohydrin (9.62g, 113mmol) was slowly added to hydroxylamine (100ml, 1.27M in EtOH) at 0 ℃. Stirring was continued at room temperature for 3 hours, and then the reaction mixture was concentrated to dryness under reduced pressure to give crude (E/Z) -N', 2-dihydroxybutyliminamide(9.1g, 68%). The crude (E/Z) -N', 2-dihydroxybutylimide (8.0g, 67.7mmol) was dissolved in pyridine (350ml) and 3-chlorobenzoyl chloride (8.72ml, 67.7mmol) was added slowly at 0 ℃. After stirring at room temperature for 1 hour, the mixture was heated to reflux overnight. After cooling to room temperature, saturated NaHCO was added₃Aqueous solution and the mixture was extracted with DCM. The organic phase was washed with water and brine, dried and concentrated. Column chromatography gave 7.15g (44%) of the title compound.¹H NMR：1.04(t，3H)2.00(m，2H)2.35(m，1H)4.87(m，1H)7.47(t，1H)7.57(m，1H)8.02(m，1H)8.14(m，1H)

[1160] Example 912

[1161] (+) - (1R) -1- [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] ethanol

[1162]

[1163]A solution of 1.53g (18.6mmol) of sodium acetate in water (12mL) was added to 3.88g (16.0mmol) of 3-chloro-N' - { [ (2R) -2-hydroxypropionyl group dissolved in ethanol (50mL) ]Oxy } benzimide. The mixture was heated at 90 ℃ for 5.5 h, then evaporated to dryness and purified by flash column chromatography (Hep/EA ═ 9/1) to give 2.3g (65%) of the title compound.¹HNMR：8.09(t，1H)，7.97(td，1H)，7.45-7.51(m，1H)，7.42(t，1H)，5.15(qd，1H)，2.57(d，1H)，1.72(d，3H)

[1164] Example 913

[1165]3- [3- (hydroxymethyl) -1, 2, 4-oxadiazol-5-yl ] benzonitrile

[1166]

[1167]Hydroxylamine (50% in water, 5.7g, 172mmol) was added dropwise to hydroxyacetonitrile (55% in water, 8.9g, 156 mmol)l) in water (100ml) and stirred at room temperature for 4 hours. The water was evaporated off, the residue was dissolved in EtOH and dried (Na)₂SO₄). A solution of 3-cyanobenzoyl chloride (9.5g, 57.1mmol) in THF (10ml) was added dropwise to the resulting slurry of crude (1E) -N', 2-dihydroxyethyleneimine amide (4.7g, 51.9mmol) and DEA (8.0g, 62.3mmol) in THF (10ml) at 0 ℃. The reaction mixture was stirred at 0 ℃ for 2 hours and Et₂O dilution and washing (NH)₄Cl aq.). With Et₂O extraction of the aqueous phase and drying (Na)₂sO₅) And (4) an organic phase. The crude (1E) -N' - [ (3-cyanobenzoyl) oxy group obtained]-2-hydroxyethylimide amide (5.0g, 22.8mmol) was dissolved in EtOH (50 ml). NaOAc (2.8g, 34.2mmol) was added and the mixture refluxed overnight. The reaction mixture was concentrated and the precipitate was recrystallized from EtOH to give the title compound (1.4 g).¹HNMR(DMSO-d6)：8.51(m，1H)，8.39(m，1H)，8.16(m，1H)，7.84(t，1H)，5.78(t，1H)，4.63(t，2H)。

[1168] Example 914

[1169] (+) - (1R) -1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] ethanol

[1170]

[1171]7.13g (26.7mmol) (+) - (1R) -1- [5- (3-chlorophenyl) - [1, 2, 4-]Oxadiazole 3-yl]Ethyl acetate and 2.33g (56.7mmol) of lithium hydroxide monohydrate were mixed with 1: 1 THF/water (10OmL) and stirred for 18 hours. Reduced to 1/2 of the volume of the mixture in vacuo, then diluted with brine and extracted with ethyl acetate. After evaporation and drying, 5.8g (97%) of the title compound are obtained.¹H NMR：8.14(s，1H)，8.02(d，1H)，7.57(d，1H)，7.47(t，1H)，5.04-5.14(m，1H)，2.42(br s，1H)，1.67(d，3H)

[1172] Example 915

[1173] (+) -1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol 3-yl ] propan-1-ol

[1174]

[1175] The title compound was synthesized in analogy to (+) - (1R) -1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] ethanol and used directly in the next step for the synthesis of (+) -4- (5- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] propoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine.

[1176] Example 916

[1177] (-) - (1S) -1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] ethanol

[1178]

[1179]Synthesis of (+) - (1R) -1- [5- (3-chlorophenyl) - [1, 2, 4] from that described]Oxadiazol-3-yl]The title compound was isolated from the reaction of ethyl ester. Separation was carried out during elution by column chromatography to give 5g (50%) of the title compound. ¹H NMR：8.14(s，1H)，8.02(d，1H)，7.57(d，1H)，7.47(t，1H)，5.04-5.14(m，1H)，2.51(d，1H)，1.67(d，3H)。

[1180] Example 917

[1181] [5- (3-chlorophenyl) -isoxazol-3-yl ] -methanol

[1182]

[1183]Lithium aluminum hydride (320mg, 8.4mmol) was slowly added to 5- (3-fluoro-phenyl) -isoxazole-3-carboxylic acid ethyl ester at room temperature(2.0g, 8.4) in THF (100 ml). After 1 hour the reaction was quenched with water and then extracted with EA. The organic phase was washed with water and brine and dried (Na)₂SO₄) Filtration and concentration. The resulting residue was purified by column chromatography using a hex with 15-40% EA to give the title compound (1.32g, 75%,).¹H NMR：7.78(s，1H)，7.68(m，1H)，7.43(m，2H)，6.63(s，1H)，4.84(d，2H)，2.23(t，1H)。

[1184] Example 918

[1185]1- [5- (3-chloro-phenyl) -isoxazol-3-yl ] -ethanol

[1186]

[1187]Step 1: 5- (3-chloro-phenyl) -isoxazole 3-carboxylic acid methyl ester: a solution of 4- (3-chloro-phenyl) -2, 4-dioxo-butyric acid ethyl ester (3.0g, 11.8mmol) and hydroxylamine hydrochloride (2.46g, 35.4mmol) in MeOH (60ml) was heated at 80 ℃ for 4 h. After cooling, the mixture was filtered and washed with cold methanol to give methyl 5- (3-chloro-phenyl) -isoxazole-3-carboxylate (2.0g, 71%).¹H NMR: 7.82(s, 1H), 7.72(m, 1H), 7.47(m, 2H), 4.03(s, 3H). Step 2: 1- [5- (3-chloro-phenyl) -isoxazol-3-yl]-ethanone: mixing magnesium methyliodide (3M in Et) in a vial equipped with a screw cap of a stir bar₂O) (0.79ml, 2.38mmol), toluene (1ml), tetrahydrofuran (0.39ml, 4.77mmol) and TEA (1ml, 7.15 mmol). After cooling to 0 ℃ a solution of methyl 5- (3-chloro-phenyl) -isoxazole-3-carboxylate (300mg, 1.19mmol) in toluene (5ml) was added and subsequently stirred at 0 ℃ for 5 h. The mixture was quenched with 1N aqueous HCl (6.5ml, 6.5mmol), diluted with toluene (35ml), washed successively with water, saturated aqueous sodium bicarbonate and brine. The organic phase was concentrated in vacuo. The separated residue was dissolved in MeOH (8ml), and 20% aqueous KOH (1ml) was added, followed by stirring at 45 ℃ for 30 minutes, and then concentrated in vacuo. The residue was dissolved in toluene (60ml) and subsequently washed with water, saturated aq. sodium bicarbonate and water. The organic phase was concentrated in vacuo. The crude residue was purified over silica gel using 2% EA in hexane to isolate the desired compound (156mg, 60%).¹H-NMR: 7.77(m, 1H), 7.66(m, 1H), 7.42(m, 2H), 6.90(s, 1H), 2.69(s, 3H). And step 3: 1- [5- (3-chloro-phenyl) -isoxazol-3-yl]-ethanol: mixing 1- [5- (3-chloro-phenyl) -isoxazol-3-yl in a vial with a screw cap equipped with a stir bar]-ethanone (100mg, 0.45mmol), sodium borohydride (34mg, 0.90mmol) and MeOH (3ml), followed by stirring at room temperature for 3 hours, quenching with water and brine, and extraction with DCM.

The combined organic phases were dried (Na)₂SO₄) Filtered and concentrated in vacuo to isolate the title compound.¹H-NMR：7.69(m，1H)，7.59(m，1H)，7.37(m，2H)，6.59(s，1H)，5.07(q，1H)，3.45(br.s，1H)，1.58(d，3H)。

[1188] Example 919

[1189] (+) - (IR) -1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] acetic acid ethyl ester

[1190]

[1191]Under the protection of argon, 12.1g (53.9mmol) of 1- [5- (3-chlorophenyl) - [1, 2, 4]]Oxadiazol-3-yl]Ethanol and 1.60g Novozyme 435^®The reaction was carried out in toluene (750 mL). After addition of 5.0mL (54.2mmol) of vinyl acetate, the reaction was carried out at room temperature overnight, followed by filtration through Celite and washing with DCM. The filtrate was purified over silica using anhydrous DCM followed by EA/Hep-1/1 solution to give 7.1g (49%) of the title compound. ¹H NMR：8.13(t，1H)，8.01(d，1H)，7.55(d，1H)，7.47(t，1H)，6.07(q，1H)，2.15(s，3H)，1.69(d，3H)

[1192] Example 920

[1193] (+) -1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] propyl acetate

[1194]

[1195]According to the formula of the reaction with (+) - (IR) -1- [5- (3-chlorophenyl) - [1, 2, 4]]Oxadiazol-3-yl]The title compound was prepared in a similar manner to ethyl acetate, with stirring at 70 ℃ for 6 hours.¹H NMR：1.00(t，3h)2.07(m，2H)2.16(s，3H)5.90(t，1H)7.46(t，1H)7.52-7.59(m，1H)7.98-8.06(m，1H)8.13(t，1H)

[1196] Example 921

[1197]3- (1-chloroethyl) -5- (3-chlorophenyl) - [1, 2, 4] oxadiazole

[1198]

[1199]5 drops of DMF was added to 1- [5- (3-chlorophenyl) - [1, 2, 4]]Oxadiazol-3-yl]Ethanol (12.3g, 54.9mmol) in SOCl₂(150mL) the reaction was heated at 70 ℃ for 5 hours. Evaporating off excess SOCl₂The residue was purified by column chromatography (Hep 100% to Hep/EA 5/1) to yield 12.4g (93%) of the title compound.¹HNMR：1.96(d，3H)5.20(q，1H)7.46(t，1H)7.59(m，1H)8.04(m，1H)8.17(t，1H)

[1200] The following examples were synthesized in analogy to 3- (1-chloroethyl) -5- (3-chlorophenyl) - [1, 2, 4] oxadiazole.

[1201] Example 924

[1202]5- (1-chloroethyl) -3- (3-chlorophenyl) - [1, 2, 4] oxadiazole

[1203]

[1204]1.80g of 3-chloro-N' -hydroxybenzylimidamide and 3.7mL of DEA were dissolved in DCM (100mL) under argon and cooled in an ice/water bath, followed by addition of 2-chloropropionyl chloride. After 1 hour at room temperature, the mixture was concentrated and the crude product was taken up in DMF (120mL) and subsequently heated at 120 ℃ for 2 hours. The mixture was concentrated on celite and purified by column chromatography (hep 100% to hep/EA 7/3) to give the title compound (1.72g, 67%). ¹H NMR：8.09(t，1H)，7.93-8.02(m，1H)7.38-7.54(m，2H)，5.22(q，1H)，2.02(d，3H)

[1205] Example 925

[1206] 5-chloromethyl-3- (3-chloro-phenyl) - [1, 2, 4] oxadiazole

[1207]

[1208]According to the formula with 5- (1-chloroethyl) -3- (3-chlorophenyl) - [1, 2, 4]]The title compound is prepared in a manner analogous to the oxadiazole procedure.¹H NMR：8-07(t，1H)，7.93-7.98(m，1H)，7.46-7.52(m，1H)，7.42(t，1H)，4.74(s，2H)

[1209] Example 926

[1210]3- [5- (chloromethyl) -1, 2, 4-oxadiazol-3-yl ] benzonitrile

[1211]

[1212]According to the formula with 5- (1-chloroethyl) -3- (3-chlorophenyl) - [1, 2, 4]]The title compound is prepared in a manner analogous to the oxadiazole procedure.¹HNMR：8.40(s，1H)，8.32(d，1H)，7.82(d，1H)，7.64(t，1H)，4.77(s，2H)。

[1213] Example 927

[1214]3- (1-chloro-ethyl) -5-m-tolyl- [1, 2, 4] oxadiazole

[1215]

[1216] 2-chloro-N-hydroxy-propionamidine (218mg, 1.78mmol) and triethylamine (0.677ml, 4.86mmol) were added to a solution of 3-methyl-benzoyl chloride (250mg, 1.62mmol) in DCM (10.0ml) at 0 deg.C and the resulting mixture was stirred for 20 min. The solution was concentrated, DMF (20ml) was added to the residue and heated at 120 ℃ for 20 minutes. The product was purified by flash chromatography using 10-20% EA in hexane to give 0.250g (59% yield between 2 steps) of the title compound. GCMS (M/Z) 222.

[1217] Example 928

[1218] 3-chloromethyl-5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole

[1219]

[1220]Step A. from 3-chlorobenzoic acid (2.82g, 18mmol), EDCl (3.46g, 18mmol), HOBt (2.76g, 18mmol) and 2-chloro-N-hydroxy-acetamidine (1.75g, 16.2mmol) [ chem. Ber.1907, 40, 1639 ]Mixture in DMF (40mL) gave the acyclic intermediate. And B: heating in DMF (40mL) gave the cyclic compound which was purified by SPE column chromatography on silica gel using 2% acetone in hexane to give the title compound (1.46g, 39% yield over 2 steps).¹H NMR：8.17(m，1H)，8.07(dd，1H)，7.60(m，1H)，7.55(t，1H)，4.69(s，2H)。

[1221] Example 929

[1222]3- [5- (chloromethyl) -1, 3, 4-oxadiazol-2-yl ] benzonitrile

[1223]

[1224]N' - (chloroacetyl) -3-cyanobenzoyl hydrazine (795mg, 3.34mmol) and P₂O₅(4.7g, 33.4mmol) was added to DMF (6ml) and toluene (4 ml). The reaction mixture was refluxed for 2 hours. Adding K₂CO₃(saturated aqueous solution) to basic pH and the mixture was extracted with DCM. Combine the organic layers (Na)₂SO₄) Dried and purified by flash chromatography using heptane containing 0-100% EA to give the title compound (209mg, 29%).¹HNMR：8.29(m，2H)，7.82(m，1H)，7.66(t，1H)，4.78(s，2H)。

[1225] Example 930

[1226] 3-cyanobenzoyl hydrazine

[1227]

[1228]3-Cyanobenzoyl chloride (4.8g, 29.0mmol) was dissolved in DCM (20ml) and MeOH (40ml) was added in portions at 0 ℃. The mixture was stirred at 0 ℃ for 1 hour and at room temperature for 2 hours. The solvent was evaporated, the crude methyl ester was dissolved in EtOH (50ml) and hydrazine (24% aqueous solution, 9ml, 45mmol) was added. The reaction mixture was refluxed for 48 hours and the solvent was evaporated (co-evaporated with water). The residue was purified by preparative HPLC to give the title compound (1.8g, 39%). ¹H NMR：(DMSO-d6)：9.98(br s，1H)，8.21(m，1H)，8.13(m，1H)，7.99(m，1H)，7.69(t，1H)，4.61(br s，2H)。

[1229] Example 931

[1230] N' - (chloroacetyl) -3-cyanobenzoyl hydrazine

[1231]

[1232]3-Cyanobenzoyl hydrazine (1.6g, 10.0mmol) was added to THF (40ml) and DMF (10 ml). TEA (1.4ml, 10.0mmol) was added at 0 deg.C followed by chloroacetyl chloride (1.0ml, 12.6mmol) and the reaction mixture was stirred at 0 deg.C for 1 hour and at room temperature for 2 hours. THF was evaporated and water was added to the residue, which was then filtered over celite and purified by preparative HPLC to give the title compound (1.6g, 69%).¹HNMR：(DMS0-d6)：10.62(br s，2H)，8.28(m，1H)，8.18(m，1H)，8.08(m，1H)，7.75(t，1H)，4.22(s，2H)。

[1233] Example 932

[1234]3- (bromomethyl) -5- (3-chlorophenyl) -1, 2, 4-oxadiazole

[1235]

[1236]Under nitrogen, 3- (chloromethyl) -5- (3-chlorophenyl) -1, 2, 4-oxadiazole (1.38g, 6.0mmol) and LiBr (0.90g, 10.3mmol) were heated to reflux in THF (50ml) overnight. Cooling to room temperature, adding EA, and reacting the organic phase with H₂Washed with brine, dried and evaporated to give the title compound (1.40g, 85%). MS (M)⁺+1)275。

[1237] Example 933

[1238]3- (bromomethyl) -5- (3-tolyl) -1, 2, 4-oxadiazole

[1239]

[1240]The title compound is prepared in analogy to 3- (bromomethyl) -5- (3-chlorophenyl) -1, 2, 4-oxadiazole. MS (M)⁺+1)253.

[1241] Example 934

[1242]3- (1-bromo-ethyl) -5- (3-chloro-phenyl) - [1, 2, 4] oxadiazole

[1243]

[1244]A solution of NBS (396mg, 2.22mmol) in THF (2ml) was added dropwise to a solution of triphenylphosphine (583mg, 2.22mmol) in THF (2ml) at 0 deg.C. After stirring for 20 minutes, 1- [5- (3-chloro-phenyl) -1, 2, 4-oxadiazol-3-yl ] -is added ]-a solution of ethanol (416mg, 1.85mmol) in THF (2 ml). Stirring was continued at room temperature overnight before removing the solvent under reduced pressure. Flash chromatography (hep/EA 6: 1) afforded 168mg (32%) of the title compound.¹H NMR：2.12(d，3H)5.21(q，1H)7.47(t，1H)7.57(m，1H)8.03(d，1H)8.15(s，1H)

[1245] Example 936

[1246]3- (1-bromoethyl) -5- (5-chloro-2-fluorophenyl) -1, 2, 4-oxadiazole

[1247]

[1248]1.6g of 1- [5- (5-chloro-2-fluorophenyl) -1, 2, 4-oxadiazol-3-yl]Ethanol was dissolved in benzene (30mL) and 0.6mL of phosphorus tribromide was added. After heating and refluxing for 90 minutes, water (C) is added15 mL). Adding solid NaHCO₃Followed by CHCl₃And (4) extracting. With Na₂SO₄After drying and removal of the solvent, purification was carried out on a 2mm chromatography plate (hep 100% to hep/EA ═ 99/1) to yield 0.60g (32%) of the title compound.¹H NMR：8.15(dd，1H)，7.49-7.59(m，1H)，7.19-7.26(m，1H)，5.23(q，1H)，2.13(d，3H)

[1249] Example 937

[1250]1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] ethyl methanesulfonate

[1251]

[1252]Methanesulfonyl chloride (40ml, 0.49mmol) was added to TEA (95ml, 0.67mmol) and 1- [5- (3-chloro-phenyl) -1, 2, 4-oxadiazol-3-yl]A mixture of ethanol (100mg, 0.45mmol) in DCM (5 ml). After stirring for 15 min, the mixture was washed with water and brine, dried and concentrated to give the title compound (135 mg).¹H NMR：1.9(d，3H)3.1(s，3H)5.9(q，1H)7.5(t，1H)7.6(m，1H)8.0(m，1H)8.1(t，1H)

[1253] The following examples were synthesized in analogy to 1- [5- (3-chlorophenyl) - [1, 2, 4] oxadiazol-3-yl ] ethyl methanesulfonate.

[1254] Example 940

[1255]5- (3-chlorophenyl) -N-methyl-1, 2, 4-oxadiazol-3-amine

[1256]

[1257]Hydroxycarboximidodibromide (2.21g, 10.89nimol) was added portionwise to 3-chlorobenzonitrile (3.00g, 21.29mmol) and NaHCO at 90 deg.C over 1 h 20 min₃(2.9g, 34.87mmol) in toluene (3 ml). Stirring was continued for 3 hours, then the reaction was cooled to room temperature, diluted with EA and washed with water. The organic phase was dried and concentrated. After flash chromatography (hex/EA 10: 1), a mixture of 3-chlorobenzonitrile and 3-bromo-5- (3-chlorophenyl) -1, 2, 4-oxadiazole was obtained. 1.0g of the mixture is dissolved in MeNH₂(4ml, 8.5M in EtOH) and heated in a microwave reactor at 60 ℃ for 30 minutes. Volatiles were removed under reduced pressure and the residue was dissolved in water and taken up in CHCl₃And (4) extracting. The organic phase was dried and concentrated. Recrystallization from EA gave 137mg of the title compound.¹HNMR：3.00(d，3H)4.35(bs，1H)7.43(t，1H)7.50-7.55(m，1H)7.92(d，1H)8.03(s，1H)

[1258] Example 941

[1259]5- (3-chlorophenyl) -N-ethyl-1, 2, 4-oxadiazol-3-amine

[1260]

[1261]The title compound was synthesized in analogy to 5- (3-chlorophenyl) -N-methyl-1, 2, 4-oxadiazol-3-amine.¹H NMR：1.28(t，3H)3.36(q，2H)7.43(t，1H)7.49-7.55(m，1H)7.92(m，1H)8.03(s，1H)

[1262] Example 942

[1263]4- [5- (chloromethyl) -4-methyl-4H-1, 2, 4-triazol-3-yl ] pyridine

[1264]

[1265]Sulfonyldichloride (0.58ml, 8.34mmol0 in DCM (8ml) was slowly added to a cooled (-10 ℃) solution of 4- (4, 5-dimethyl-4H-1, 2, 4-triazol-3-yl) pyridine (454mg, 2.61mmol) in DCM (25ml) and DMF (8ml) and the solution was stirred for 2H, NaHCO was added ₃(saturation) the mixture was extracted with EA. The organic phase was dried and concentrated. Recrystallization from EA gave 124mg (23%) of the title compound.¹H NMR：3.83(s，3H)4.84(s，2H)7.62(d，2H)8.82(d，2H)。

[12661 preparation of the Final Compound

[1267] Example 943

[1268]4- (5- {2- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] propyl } -4-cyclopropyl-4H-1, 2, 4-triazol-3-yl) pyridine

[1269]

[1270]n-BuLi (210ml, 2.5M in hexanes, 0.52mmol) was added dropwise to a solution of 4- (4-cyclopropyl-5-methyl-4H-1, 2, 4-triazol-3-yl) pyridine (80mg, 0.4mmol) in THF (10ml) at-78 deg.C under a nitrogen atmosphere. After stirring for 15 minutes, 3- (1-bromo-ethyl) -5- (3-chloro-phenyl) - [1, 2, 4] was added]Oxadiazole (115mg, 0.4mmol) in THF (2 ml). The mixture was stirred at-78 ℃ for 2 hours and then at room temperature for 1 hour. The solvent was removed under reduced pressure and preparative HPLC was used to obtain 20 mg of the desired compound.¹H NMR：0.7(m，2H)1.2(ddd，2H)1.6(d，3H)3.2(dd，1H)3.3(ddd，1H)3.6(dd，1H)3.9(m，1H)7.5(t，1H)7.6(m，1H)7.7(m，2H)8.0(m，1H)8.1(t，1H)8.7(m，2H)

[1271] The following example was synthesized in analogy to 4- (5- {2- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] propyl } -4-cyclopropyl-4H-1, 2, 4-triazol-3-yl) pyridine:

[1272] example 950

[1273]3- (3-chloro-phenyl) -5- {2- [ 3-chloropropyl-2- (4-methoxy-phenyl) -3H-imidazol-4-yl ] -ethyl } - [1, 2, 4] oxadiazole

[1275]3-chloro-N' -hydroxybenzeneimidamide (54.3mg, 0.32mmol), 3- [ 3-cyclopropyl-2- (4-methoxy-phenyl) -3H-imidazol-4-yl ]Ethyl propionate (100mg, 0.32mmol) and sodium tert-butoxide (30.6mg, 0.32mmol) were mixed in EtOH (1ml) and toluene (1ml) and subsequently stirred at 100 ℃ for 24 h. The mixture was then concentrated in vacuo and the residue was purified by column chromatography using 50% EA in hexane and then Et₂Trituration with O isolated the title compound (27 mg).¹H-NMR：8.1(m，1H)，7.97(dd，1H)，7.64(d，2H)，7.47(m，2H)，6.96(d，2H)，6.88(s，1H)，3.87(s，3H0，3.37(m，4H)，3.24(m，1H)，1.06(m，2H)，0.68(m，2H)。

[1276] Example 951

[1277]3- (3-chloro-phenyl) -5- {2- [ 3-cyclopropyl-2- (4-methoxy-phenyl) -3H-imidazol-4-yl ] -1-methyl-ethyl } - [1, 2, 4] oxadiazole

[1279]According to the formula with 3- (3-chloro-phenyl) -5- {2- [ 3-cyclopropyl-2- (4-methoxy-phenyl) -3H-imidazol-4-yl]-ethyl } - [1, 2, 4]The title compound was synthesized in a manner analogous to the oxadiazole procedure.¹H-NMR：8.1(m，1H)，7.98(dd，1H)，7.63(d，2H)，7.46(m，2H)，6.97(d，2H)，6.85(s，IH)，3.88(s，3H)，3.65(m，IH)，3.42(m，IH)，3.15(m，2H)，1.58(d，3H)，1.06(m，2H)，0.67(m，2H)。

[1280] Example 952

[1281]4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -propyl } -1-cyclopropyl-1H-imidazol-2-yl) -pyridine

[1283]3-chloro-N-hydroxy-benzamidine (486mg, 2.85mmol), 3- (3-cyclopropyl-2-pyridin-4-yl-3H-imidazol-4-yl) -2-methyl-propionic acid (702mg, 2.59mmol), EDCl (546mg, 2.85mmol) and HOBt hydrate (385mg, 2.85mmol) were mixed with DMF (20ml) and stirred at room temperature overnight. The reaction was diluted with water and extracted with EA. The combined organic phases were washed successively with saturated aqueous sodium bicarbonate, brine and dried (Na) ₂SO₄) Filtered and concentrated in vacuo. The residue was heated at 120 ℃ in DMF (10ml) for 2 h. The reaction mixture was cooled to room temperature, diluted with EA (50ml), washed successively with water, brine and dried (Na)₂SO₄) Filtered and concentrated in vacuo. The crude product was purified by column chromatography using 2% MeOH in DCM to isolate the title compound (404 mg).¹H-NMR：8.69(dd，2H)，8.09(m，1H)，7.96(d，1H)，7.67(dd，2H)，7.46(m，2H)，6.94(s，1H)，3.66(m，1H)，3.48(m，1H)，3.31(m，1H)，3.16(m，1H)，1.59(d，3H)，1.19(m，2H)，0.72(m，2H)。

[1284] Example 953

[1285]3- (3-chloro-phenyl) -5- {2- [2- (4-methoxy-phenyl) -3-methyl-3H-imidazol-4-yl ] -1-methyl-ethyl } - [1, 2, 4] oxadiazole

[1286]

[1287]According to the formula of the compound and 4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4]]Oxadiazol-5-yl]The title compound was synthesized in analogy to-propyl } -1-cyclopropyl-1H-imidazol-2-yl) -pyridine.¹H-NMR：8.1(m，1H)，7.98(dd，1H)，7.50(m，4H)，6.97(d，2H)，6.92(s，1H)，3.87(s，3H)，3.62(s，3H)3.54(m，1H)，3.30(m，1H)，3.00(m，1H)，1.57(d，3H)。

[1288] Example 954

[1289] (S) -4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4] oxadiazol-5-yl ] -propyl } -4-cyclopropyl-4H- [1, 2, 4] triazol-3-yl) -pyridine

[1294]

[1291]3-chloro-N-hydroxy-benzamidine (0.7g, 4.1mmol) and potassium tert-butoxide (0.373g, 3.33mmol) in N-propanol at 80 ℃ for 10 minutes, 3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4]Triazol-3-yl) -2-methyl-propionic acid ethyl ester (1.0g, 3.33mmol) was added to the reaction mixture and heated at 100 ℃ for 3 hours. The reaction mixture was concentrated and quenched with saturated ammonium chloride and extracted with DCM. With MgSO ₄Drying the organic layer, purifying by column chromatography, and treating with Et₂Trituration afforded rac 4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-propyl } -4-cyclopropyl-4H- [1, 2, 4]Triazol-3-yl) -pyridine (0.8g, 59%). The title product was isolated by isolation in Chiracel OJ using EtOH: hex. (1: 4):¹H-NMR: 8.78(d, 2H), 8.05(s, 1H), 7.96(d, 1H), 7.74(d, 2H), 7.50(d, 1H), 7.43(t, 1H), 4.15(m, 1H), 3.64(dd, 1H), 3.31(m, 2H), 1.67(d, 3H), 1.25(m, 2H) and 0.78(m, 2H).

[1292] Example 955

[1293] 4- (5- { (2S) -2- [5- (3-chlorophenyl) -1, 3, 4-oxadiazol-2-yl ] propyl } -4-cyclopropyl-4H-1, 2, 4-triazol-3-yl) pyridine

[1294]

[1295]In a sealed flask at 120 deg.C, 3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4)]Triazol-3-yl) -2-methyl-propionic acid ethyl ester (2.14g, 7.1mmol) was mixed with hydrazine monohydrate in ethanol for 2 hours. The reaction mixture was concentrated and triturated with ether to give 3- (4-cyclopropyl-5-pyridin-4-yl-4H- [1, 2, 4)]Triazol-3-yl) -2-methyl-propionylhydrazide. This compound was mixed with 3-chloro-benzylidene amino acid ethyl ester hydrochloride (0.722g, 7.8mmol) in ethanol at 130 ℃ overnight. The reaction mixture was concentrated, quenched with saturated sodium carbonate and extracted with DCM. The organic layer was dried with 5% methanol (2M NH) ₃) The DCM solution was purified by column chromatography to give racemic 4- (5- {2- [3- (3-chloro-phenyl) - [1, 2, 4 ]]Oxadiazol-5-yl]-propyl } -4-cyclopropyl-4H [1, 2, 4 ]]Triazol-3-yl) -pyridine 1.19g (41.1%). This material (70mg) was separated on Chiralpak AD using ethanol as eluent to give the title compound.¹H-NMR: 8.77(d, 2H), 8.02(s, 1H), 7.92(d, 1H), 7.72(d, 2H), 7.51(d, 1H), 7.47(t, 1H), 4.12(m, 1H), 3.69(dd, 1H), 3.44(m, 1H), 3.26(dd, 1H), 1.66(d, 3H), 1.24(m, 2H) and 0.79(m, 2H).

[1296] Example 956

[1297]4- (5- { (2R) -2- [5- (3-chlorophenyl) -1, 3, 4-oxadiazol-2-yl ] propyl } -4-cyclopropyl-4H-1, 2, 4-triazol-3-yl) pyridine

[1299] The title compound was isolated by chiral LC from example 4- (5- { (2S) -2- [5- (3-chlorophenyl) -1, 3, 4-oxadiazol-2-yl ] propyl } -4-cyclopropyl-4H-1, 2, 4-triazol-3-yl) pyridine.

[1300] Example 957

[1301]4- (5- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine

[1302]

[1303]Under an argon atmosphere, 1.45g (6.08mmol) of 4- [ 4-methyl-5- (methylsulfonyl) -4H-1, 2, 4-triazol-3-yl]Pyridine, 1.73g (7.70mmol)1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ]Ethanol and 4.03g (12.3mmol) cesium carbonate were dissolved in DMF (25mL) and stirred at 30 ℃ for 3 days. After filtration and evaporation to dryness, the crude product was purified on a 4mm silica gel chromatography plate (DCM/MeOH-100/0-90/10). Further purification on a 2mm silica gel chromatography plate (Hep/EA/MeOH-15/15/1) afforded 0.36g (15%) of the title compound.¹H-NMR：8.75(br s，2H)，8.12(s，1H)，8.00(d，1H)，7.64(d，2H)，7.56(d，1H)，7.46(t，1H)，6.39(q，1H)，3.63(s，3H)，1.94(d，3H)。

[1304] The following examples were synthesized in analogy to 4- (5- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine.

[1306] (-) -4- (5- {1- [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine

[1308]0.57g (2.54mmol) (+) - (1R) -1- [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl]Ethanol, 0.64g (2.68mmol)4- [ 4-methyl-5- (methylsulfonyl) -4H-1, 2, 4-triazol-3-yl]Pyridine and 0.90g (2.76mmol) cesium carbonate were stirred at 65 ℃ for 6 hours, followed by dilution with water. Extracting with EA, washing with citric acid aqueous solution, and adding Na₂SO₄Drying and subsequent purification on a 2mm thin layer centrifuge plate (Hep/EA/MeOH. RTM. 10/10/1) gave 0.81g (83%) of racemic 4- (5- {1- [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl)]Ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine. Preparative chiral separation using 100% 2-propanol in Chiralpak AD yielded 0.25g of the title compound as the second eluting enantiomer. ¹H-NMR：8.76(d，2H)，8.07(t，1H)，7.92-7.99(m，1H)，7.60-7.68(m，2H)，7.45-7.51(m，1H)，7.41(t，1H)，6.45(q，1H)，3.66(s，3H)，1.99(d，3H)

[1309] Example 967

[1310] (+) -4- (5- {1- [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine

[1312]In the example (-) -4- (5- {1- [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl]Ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine, 0.2g of the title compound was isolated as the first eluting enantiomer during the preparative chiral HPLC separation.¹H-NMR：8.77(d，2H)，8.07(t，1H)，7.93-8.00(m，1H)，7.68(dd，2H)，7.45-7.52(m，1H)，7.41(t，1H)，6.45(q，1H)，3.67(s，3H)，1.99(d，3H)

[1313]Example 968

[1314]4- (5- {1- [5- (3-chloro-phenyl) -isoxazol-3-yl ] -ethoxy } -4-methyl-4H- [1, 2, 4] triazol-3-yl) -pyridine

[1316]1- [5- (3-chloro-phenyl) -isoxazol-3-yl]Ethanol (63.4mg, 0.28mmol), DMF and sodium hydride (60% oil dispersion, 15.1mg, 0.38mmol) were mixed under an inert gas atmosphere and stirred at room temperature for 1 hour, followed by addition of 4- [ 4-methyl-5- (methylsulfonyl) -4H-1, 2, 4-triazol-3-yl]Pyridine (45mg, 0.19 mmol). After stirring at 80 ℃ for 24 hours, the mixture was cooled to room temperature, diluted with EA and washed successively with water and brine. The organic phase was dried (Na)₂SO₄) Filtered and concentrated in vacuo. The crude residue was purified by column chromatography using 5% MeOH in EA to isolate the title compound (11.7 mg).¹H-NMR：8.81(bs，2H)，7.77(s，1H)，7.67(m，3H)，7.42(m，2H)，6.73(s，1H)，6.36(q，1H)，3.62(s，3H)，1.94(d，3H)。

[1317] Example 969

[1318] N- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -N, 4-dimethyl-5-pyridin-3-yl-4H-1, 2, 4-triazol-3-amine

[1319]

[1320]NaH (14mg, 0.35mmol) was added to a solution of N, 4-dimethyl-5-pyridin-3-yl-4H-1, 2, 4-triazol-3-amine (33mg, 0.18mmol) in DMF (3 mL). After 30 min, a solution of 3- (1-chloroethyl) -5- (3-chlorophenyl) -1, 2, 4-oxadiazole (80mg, 0.18mmol) in DMF (1mL) was added to the mixture and the reaction stirred at 60 ℃ overnight. Brine was added and the mixture was extracted with EA. The organic phase was dried and concentrated. Purification by column chromatography (DCM to DCM-MeOH 30: 1) gave 31mg (43%) of the title compound.¹H-NMR：1.71(d，3H)2.97(s，3H)3.67(s，3H)4.88(q，1H)7.46(m，2H) 7.56(d，1H)8.00(d，1H)8.10(d，2H) 8.71(bs，1H)8.92(bs，1H)

[1321] The following examples were synthesized in analogy to N- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -N, 4-dimethyl-5-pyridin-3-yl-4H-1, 2, 4-triazol-3-amine.

[1322] Example 974

[1323] (+) -N- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -5- (3, 5-difluorophenyl) -N, 4-dimethyl-4H-1, 2, 4-triazol-3-amine

[1324]

[1325]To a solution of 5- (3, 5-difluorophenyl) -N, 4-dimethyl-4H-1, 2, 4-triazol-3-amine (0.47g, 2.10mmol) in DMF (10ml) at room temperature under nitrogen was added NaH (77mg, 3.20 mmol). After stirring for 15 minutes, 1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] is added]Ethyl methanesulfonate (0.70g, 2.30mmol) in 10ml DMF. After 3 hours, use NH ₄The mixture was diluted with a saturated solution of Cl and then extracted with EA. The organic phase was washed with water and brine, dried and evaporated. Purification by silica gel chromatography using hex 1: 1 EA to give 400mg of racemic N- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl]Ethyl } -5- (3, 5-difluorophenyl) -N, 4-dimethyl-4H-1, 2, 4-triazol-3-amine, which was isolated by using preparative chiral HPLC on a chiralpak ad column (hex./2-propanol 80/20 to 100% 2-propanol) to give 183 mg (21%) of the title compound, which was eluted last.¹H-NMR：1.68(d，3H)2.89(s，3H)3.62(s，3H)4.79(q，1H)6.80-6.90(m，1H)7.19(d，2H)7.40(t，1H)7.49(d，1H)7.94(d，1H)8.04(s，1H)

[1326] Example 975

[1327] (-) -N- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -5- (3, 5-difluorophenyl) -N, 4-dimethyl-4H-1, 2, 4-triazol-3-amine

[1329]In the preparation of (+) -N- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl]In the example of ethyl } -5(3, 5-difluorophenyl) -N, 4-dimethyl-4H-1, 2, 4-triazol-3-amine, 186mg of the title compound were isolated as the first eluting enantiomer during preparative chiral HPLC.¹H-NMR：1.68(d，3H)2.89(s，3H)3.62(s，3H)4.79(q，1H)6.80-6.90(m，1H)7.19(d，2H)7.40(t，1H)7.49(d，1H)7.94(d，1H)8.04(s，1H)。

[1330] Example 976

[1331] (+) -8- { (1S) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4] triazolo [4, 3-a ] pyrimidine

[1332]

[1333]NaH (716mg, 29.8mmol) was slowly added to 3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4] -under nitrogen ]Triazole [4, 3-a ]]A solution of pyrimidine (5.0g, 24.8mml) in DMF (250 ml). After 10 min, a solution of 3- (1-chloroethyl) -5- (3-chlorophenyl) -1, 2, 4-oxadiazole (6.0g, 24.8mmol) in DMF (200ml) was added, followed by stirring at room temperature overnight. Addition of NH₄After saturating the solution with Cl, water was added. The mixture was extracted with EA and DCM. The combined organic extracts were washed with water and brine, dried and concentrated. Recrystallization from EA gave 2.24g (22%) of the racemic product 8- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl]Ethyl } -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4] c]Triazole [4, 3-a ]]A pyrimidine. The title compound was isolated as the second enantiomer which eluted on a Chiralpak AD (100% 2-propanol) column.¹H-NMR：1.74(d，3H)2.17(m，2H)3.45(m，2H)4.10(m，2H)5.96(m，1H)7.44(t，1H)7.53(m，1H)7.59(m，2H)7.97(m，1H)8.08(m，1H)8.67(d，2H)

[1334] Example 977

[1335] (-) -8- { (1R) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4] triazolo [4, 3-a ] pyrimidine

[1336]

[1337]At (+) -8- { (1S) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl]Ethyl } -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4] c]Triazole [4, 3-a ]]Process for preparing pyrimidinesIn the examples, the title compound was isolated as the first eluting enantiomer during preparative chiral HPLC.¹H-NMR：1.74(d，3H)2.17(m，2H)3.45(m，2H)4.10(m，2H)5.96(m，1H)7.44(t，1H)7.53(m，1H)7.59(m，2H)7.97(m，1H)8.08(m，1H)8.67(d，2H)

[1338] Example 978

[1339] (-) -N- {1- [3 (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine

[1340]

[1341]Preparative chiral HPLC on Chiralpak AD (100% 2-propanol) isolated as the last eluting isomer afforded the title compound.¹H-NMR：8.74(s，2H)，8.05(t，1H)，7.87-8.00(m，1H)，7.56-7.69(m，2H)，7.32-7.53(m，2H)，5.03(q，1H)，3.68(s，3H)，2.98(s，3H)，1.81(d，3H)

[1342] Example 979

[1343] (+) -N- {1- [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine

[1344]

[1345]Preparative chiral HPLC on Chiralpak AD (100% 2-propanol) isolated as the first eluting isomer yielded the title compound.¹H-NMR：8.74(s，2H)，8.05(t，1H)，7.87-8.00(m，1H)，7.56-7.69(m，2H)，7.32-7.53(m，2H)，5.03(q，1H)，3.68(s，3H)，2.98(s，3H)，1.81(d，3H)

[1346] Example 980

[1347] (-) -N- { (1S) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine

[1348]

[1349] Racemic N- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine was isolated by preparative chiral HPLC on Chiralpak AD (100% 2-propanol) to give the title compound. It is finally eluted.

[1350] Example 981

[1351] (+) -N- { (1R) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine

[1352]

[1353] In the example of preparative chiral HPLC isolation of (-) -N- { (1S) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine, the title compound was isolated as the first eluting enantiomer.

[1354] Example 982

[1355]3- [5- (3-pyridin-4-yl-6, 7-dihydro-5H- [1, 2, 4] triazolo [4, 3-a ]) pyrimidin-8-ylmethyl ] [1, 3, 4] oxadiazol-2-yl ] benzonitrile

[1356]

[1357]3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4]Triazole [4, 3-alpha ]]Pyrimidine (172mg, 0.85mmol) and 3- [5- (chloromethyl) -1, 3, 4-oxadiazol-2-yl]Benzonitrile (94mg, 0.43mmol) was dissolved in butanone (5ml) and K was added₂CO₃(118mg, 0.85mmol) and KI (35mg, 0.21 mmol). The reaction mixture was refluxed for 1 hour and the solvent was evaporated. The residue is dissolved in K₂CO₃(aq, 1M, 25ml) and extracted with DCM. The combined organic layers were dried (Na)₂SO₄) Purification by preparative HPLC gave the title compound (27mg, 16%). 1H-NMR: 8.75(d, 2H), 8.30(m, 2H), 7.79(d, 1H), 7.63(m, 1H), 7.53(dd, 2H), 5.57(d, 2H), 4.06(t, 2H), 3.58(t, 2H), 1.99(m, 2H).

[1358] The following compounds are prepared in analogy to 3- [5- (3-pyridin-4-yl-6, 7-dihydro-5H- [1, 2, 4] triazolo [4, 3- α ] pyrimidin-8-ylmethyl) [1, 3, 4] oxadiazol-2-yl ] benzonitrile.

[2225] Examples of the embodiments

[1359] Example 986

[1360]3- {3- [ (3-pyridin-4-yl-6, 7-dihydro [1, 2, 4] triazolo [4, 3-a ] pyrimidin-8 (5H) -yl) methyl ] -1, 2, 4-oxadiazol-5-yl } benzonitrile

[1361]

[1362][5- (3-cyanophenyl) -1, 2, 4-oxadiazol-3-yl]Methyl methanesulfonate (0.278 g; 0.99mmol) and 3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4-d]Triazole [4, 3-alpha ]]Pyrimidine (0.220 g; 1.09mmol) was dissolved in butanone (20ml), and potassium carbonate (0.275 g; 1.99mmol) was added in portions. Heated at reflux for 18 hours before cooling to room temperature. The mixture was concentrated in vacuo and DCM (20ml) was added. The mixture was washed with water and dried (Na)₂SO₄) Evaporation and purification using preparative HPLC chromatography gave the title compound (5.4 mg).¹H-NMR：8.77(m，2H)，8.41(s，1H)，8.34(d，1H)，7.87(d，1H)，7.68(t，1H)，7.56(m，2H)5.51(s，2H)，4.09(m，2H)，3.62(m，2H)，2.19(m，2H)。

[1363] Example 987

[1364]3- (3- { [ [5- (2-methoxypyridin-4-yl) -4-methyl-4H-1, 2, 4-triazol-3-yl ] (methyl) amino ] methyl } -1, 2, 4-oxadiazol-5-yl) benzonitrile

[1365]

[1366]Sodium hydride (0.013g, 0.53mmol) was added in portions to a stirred solution of 5- (2-methoxypyridin-4-yl) -N, 4-dimethyl-4H-1, 2, 4-triazol-3-amine (0.086 g; 0.39mmol) in DMF (10ml) at 10 ℃. The mixture was stirred for 30 minutes and 5- (3-cyanophenyl) -1, 2, 4-oxadiazol-3-yl was added dropwise]A solution of methyl methanesulfonate (0.1g, 0.36mmol) in DMF (1 ml). The mixture was stirred at room temperature for 3 hours before quenching with water (30 ml). The resulting mixture was extracted with EA (3 × 40 ml). The organic phases are combined and dried (Na)₂SO₄) And evaporated to give the crude product, which was purified by preparative HPLC to give the title compound (0.061 g; 42.3%). ¹H-NMR：8.49(s，1H)，8.33((dd，1H)，8.28(d，1H)，7.86(dd，1H)，7.67(t，1H)，7.24(d，1H)，7.02(s，1H)，4.60(s，2H)，3.97(s，3H)，3.70(s，3H)，3.08(s，3H)。

[1367] The following examples are prepared in analogy to 3- (3- { [ [5- (2-methoxypyridin-4-yl) -4-methyl-4H-1, 2, 4-triazol-3-yl ] (methyl) amino ] methyl } -1, 2, 4-oxadiazol-5-yl) benzonitrile.

[1368] Example 991

[1369]3- {5- [ (3-pyridin-4-yl-6, 7-dihydro [1, 2, 4] triazolo [4, 3-a ] pyrimidin-8 (5H) -yl) methyl ] -1, 2, 4-oxadiazol-3-yl } benzonitrile

[1370]

[1371]3- [5- (chloromethyl) -1, 2, 4-oxadiazol-3-yl]Benzonitrile (98.2mg, 0.447mmol) and 3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4]]Triazole [4, 3-a ]]Pyrimidine (62.2mg, 0.309mmol) was suspended in acetonitrile (2ml) and isopropanol (2.4 ml). After stirring for 45 minutes, potassium carbonate (88.1mg, 0.637mmole) was added. The mixture was heated in a microwave oven (130 ℃ C.) for 30 minutes. The product was filtered and then purified on preparative HPLC to give 29mg of the title compound.¹H-NMR(DMSO-d6)：8.72(dd，2H)，8.36(br t，1H)，8.30(dt，1H)，8.08(dt，1H)，7.79(t，1H)，7.68(dd，2H)，5.49(s，2H)，4.02(t，2H)，3.3(m，1H)，2.36(s，3H)，1.71(t，2H)。

[1372] Example 992

[1373]3- {5- [3- (2-hydroxy-pyridin-4-yl) -6, 7-dihydro-5H- [1, 2, 4] triazolo [4, 3-a ] pyrimidin-8-ylmethyl ] - [1, 2, 4] oxadiazol-3-yl } -benzonitrile

[1374]

[1375]According to the formula of the compound and 3- {5- [ (3-pyridin-4-yl-6, 7-dihydro [1, 2, 4]]Triazole [4, 3-a ]]Pyrimidin-8 (H) -yl) methyl]The title compound was synthesized analogously to (E) -1, 2, 4-oxadiazol-3-yl) benzonitrile. ¹H-NMR：8.34(s，1H)，8.29(d，1H)，7.79(d，1H)，7.67(t，1H)，7.38(d，1H)，6.97(m，1H)，6.72(s，1H)，5.13(s，2H)，4.22(m，2H)，3.64(m，2H)，2.27(m，2H)

[1376] Example 993

[1377] N- { [3- (3-chlorophenyl ] -1, 2, 4-oxadiazol 5-yl } methyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine

[1378]

[1379]1- [3- (3-chloro-phenyl) - [1, 2, 4 ] at 85 deg.C]Oxadiazol-5-ylmethyl]-1, 2, 3-trimethyl-isothiourea (55mg, 0.177mmol) was mixed with isonicotinyl hydrazide (29.1mg, 0.212mmol) in ethanol (1 mL). The reaction mixture was diluted with DCM and washed with water. The product was purified by column chromatography using 5-7% MeOH in EA and Et₂Trituration with O afforded the title compound (22.5mg, 40%).¹H-NMR：8.80(d，2H)，8.10(s，1H)，8.00(d，1H)，7.66(d，2H)，7.51(d，1H)，7.47(t，1H)，4.80(s，2H)，3.74(s，3H)，3.15(s，3H)。

[1380] The following examples were synthesized in analogy to N- { [3- (3-chlorophenyl) -1, 2, 4-oxadiazol-5-yl ] methyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine.

[1381] Example 1002

[1382] N- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] -1-methylethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine

[1383]

[1384]n-BuLi (132ml 2.5M in hex. 0.33mmol) was added to diisopropylamine (55ml, 0.39 mmol). After stirring at 0 ℃ for 20 minutes, the mixture is cooled to-78 ℃ and N- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] is added]Ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine (110mg, 0.28 mmol). After 15 min methyl iodide (20. mu.l, 0.33mmol) was added and the temperature was raised to room temperature. After stirring for 2 hours 5 drops of water were added. After removal of the solvent in vacuo, the crude product was taken up in DCM, washed with water and brine, dried and concentrated. Preparative HPLC gave 20mg of the expected product. ¹H-NMR：1.7(s，6H)2.8(s，3H)3.8(s，3H)7.5(t，1H)7.6(d，1H)7.7(s，2H)8.0(d，1H)8.1(s，1H)8.8(s，2H)

[1385] Example 1003

[1386]4- (5- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] -1-methylethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine

[1387]

[1388]To a solution of diisopropylamine (55.0ml, 0.39mmol) in THF (3ml) was slowly added nBuLi (2.5M, hex., 135ml) at 0 ℃. After 20 min, the mixture was cooled to-78 ℃ and (-) -4- (5- { (1R) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl-is added]A solution of ethoxy } -4-methyl-4H-1, 2, 4-triazol-3-yl) pyridine (107mg, 0.28mmol) in THF (2 ml). After the resulting mixture was stirred for 45 min, CH3I (22ml, 0.34mmol) was added and the reaction stirred at room temperature for 1 h. Addition of NH₄The solution was saturated with Cl and extracted with EA. H for organic phase₂O and brine, dried and evaporated. Using CHCl₃The residue was purified by silica gel with MeOH 50: 1 followed by preparative HPLC to give the title compound (22mg, 20%).¹H-NMR：2.11(s，6H)3.63(s，3H)7.45(d，1H)7.52-7.57(m，1H)7.59(d，2H)7.98(d，1H)8.09(s，1H)8.72(d，2H)

[1389] Example 1004

[1390] N- { (1S) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -4-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine

[1391]

[1392]N- { (1S) -1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl]Ethyl } -N, 4-dimethyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-amine (3.1mg, 7.8mmol) and human microsomal protein (from a subject containing 70% 3A4) were cultured in 50% acetonitrile phosphate buffer solution at pH7.4 for 3 hours, and then concentrated under reduced pressure. With CHCl ₃The mixture is extracted. Drying and concentrating the organic extract. Purification by preparative HPLC afforded 0.5mg (16%) of the title compound.¹H-NMR：1.77-1.83(d，3H)3.60(s，3H)5.38-5.48(m，1H)7.48(m，1H)7.54-7.62(m，2H)8.01(m，1H)8.12(m，1H)8.74(s，2H)。

[1393] Example 1005

[1394]5- (3-chlorophenyl) -N-methyl-N- [ (4-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-yl) methyl ] -1, 2, 4-oxadiazol-3-amine

[1395]

[1396]NaH (7.0mg, 0.35mmol) was added to a solution of 5- (3-chlorophenyl) -N-methyl-1, 2, 4-oxadiazol-3-amine (60mg, 0.29mmol) in DMF (3ml) at room temperature. After 5 minutes, 4- [5- (chloromethyl) -4-methyl-4H-1, 2, 4-triazol-3-yl dissolved in DMF (3ml) was added]Pyridine (60mg, 0.29 mmol). The reaction mixture was stirred at room temperature for 4 hours. Adding saturated NH₄Aqueous Cl and the mixture extracted with EA. H for organic phase₂O and brine, dried and evaporated. Flash chromatography (DCM/MeOH 20: 1) afforded 60mg (54%) of the title compound.¹H-NMR：3.12(s，3H)3.80(s，3H)4.94(s，2H)7.46(t，1H)7.56(m，1H)7.58-7.63(m，2H)7.95(m，1H)8.06(t，1H)8.79(m，2H)。

[1397] Example 1006

[1398]5- (3-chlorophenyl) -N-ethyl-N- [ (4-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-yl) methyl ] -1, 2, 4-oxadiazol-3-amine

[1399]

[1400]According to the formula with 5- (3-chlorophenyl) -N-methyl-N- [ (4-methyl-5-pyridin-4-yl-4H-1, 2, 4-triazol-3-yl) methyl]The title compound is prepared analogously to 1, 2, 4-oxadiazol-3-amine.¹H-NMR：1.21(t，3H)3.53(q，2H)3.78(s，3H)4.95(s，2H)7.46(d，1H)7.53(d，1H)7.59(m，2H)7.95(m，1H)8.05(m，1H)8.77(d，2H)。

[1401] Example 1007

[1402] 3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4] triazolo [4, 3-a ] pyridine-8-carboxylic acid ethyl ester

[1403]

[1404]With 3-pyridin-4-yl-6, 7-dihydro-5H-pyrrolo [2, 1-c][1，2，4]Triazole analogously, from 2-oxopiperidine-3-carboxylic acid ethyl ester (2.57g, 15mmol), Me₃OBF₄(2.66g, 18mmol) and isonicotinyl hydrazide (2.06g, 15mmol) in DCM (150ml) and EtOH (16ml) were prepared. Recrystallization from EA yielded 1.67g (41%).¹H-NMR：1.29(t，3H)，2.03(m，1H)，2.14-2.25(m，2H)，2.32(m，1H)，4.01-4.12(m，1H)，4.16-4.27(m，4H)，7.64(d，2H)，8.74(d，2H)

[1405] Example 1008

[1406]3- (1-chloroethyl) -5- (3-chlorophenyl) -1, 2, 4-oxadiazole

[1407]

[1408]5 drops of DMF are added to 1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl]Ethanol (12.3g, 54.9mmol) in SOCl₂(150mL) the reaction was heated at 70 ℃ for 5 h. Evaporation of excess SOCl₂The residue is purified by column chromatography (Hep to Hep-EA 5: 1) to yield 12.4g (93%) of the title compound.¹H-NMR：1.96(d，3H)5.20(q，1H)7.46(t，1H)7.59(m，1H)8.04(m，1H)8.17(t，1H)

[1409] Example 1009

[1410]8- {1- [5- (3-chlorophenyl) -1, 2, 4-oxadiazol-3-yl ] ethyl } -3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4] triazolo [4, 3-a ] pyridine-8-carboxylic acid ethyl ester

[1411]

[1412]3-pyridin-4-yl-5, 6, 7, 8-tetrahydro [1, 2, 4]Triazolo [4, 3-alpha ]]A solution of pyridine-8-carboxylic acid ethyl ester (182mg, 0.67mmol) in DMF (2ml) was added to a stirred mixture of NaH (20mg, 0.81mmol) in DMF (2 ml). After 45 min, a solution of 3- (1-chloroethyl) -5- (3-chlorophenyl) -1, 2, 4-oxadiazole (180mg, 0.74mmol) in DMF (1ml) was added and the resulting solution was stirred at 65 ℃ for 3 h and then cooled to room temperature. Addition of NH ₄The aqueous solution was saturated with Cl and the mixture was extracted with EA. H for organic phase₂O and brine, dried and evaporated. Column chromatography (DCM/MeOH 20: 1) afforded 207mg (65%) of the title compound as a mixture of diastereomeric isomers.¹H-NMR：1.27(t，3H)，1.34(t，3H)，1.48(d，3H)，1.55(d，3H)，2.15(m，2H)，2.18(m，4H)，2.61(m，2H)，4.00(m，2H)，4.18-4.29(m，4H)，4.30-4.40(m，2H)，4.55(q，1H)，4.65(q，1H)，7.37(t，1H)，7.44(t，1H)，7.50(m，1H)，7.55(m，1H)，7.63(d，2H)，7.69(d，2H)，7.83(m，1H)，7.92(m，1H)，7.95(m，1H)，8.05(m，1H)，8.75(d，2H)，8.76(d，2H)

[14131 pharmaceutical examples

[1414]FLIPR assay for class I receptor antagonist activity

[1415]For FLIPR assays, cells were seeded on the bottom of collagen-coated clear-band black-edged 96-well plates 24 hours after seeding [ Ca²⁺]_iAnd (5) mobility analysis. Cell cultures in 96-well plates loaded with 4. mu.M methyl acetate solution to form fluorescent calcium fingers in 0.01% polyetherIndicator fluor-3(Molecular Probes, Eugene, Oregon). All tests were carried out in the presence of 127mM NaCl, 5mM KCl, 2mM MgCl₂、0.7mM NaH₂PO₄、2mM CaCl₂、0.422mg/mlNaHCO₃2.4mg/ml HEPES, 1.8mg/ml glucose and 1mg/ml BSA FractionIV (pH 7.4).

[1416] FLIPR experiments were performed using a 0.800W laser device and a 0.4 second CCD camera shutter speed, with excitation and emission wavelengths of 488nm and 562nm, respectively. Each FLIPR assay was started with 160 μ L of buffer present per well on the cell plate. 40 μ L was added from the antagonist plate followed by 50 μ L from the agonist plate. After each addition, the fluorescence signal was sampled 50 times at 1 second intervals, followed by 3 times at 5 second intervals. The reaction during sampling was measured as the peak height of the reaction.

[1417]EC₅₀/IV_5OMeasurements were taken from data obtained from 8 points of Concentration Response Curves (CRC) repeated twice. CRC for agonists was obtained by scaling the maximal response observed in all reaction plates. Blockade of agonist stimulation by the antagonist was normalized to the average response of the agonist in 14 control wells of the sample plate.

[1418] Measurement of inositol triphosphate (IP3) turnover in intact cells

[1419]GHEK stably expressing human mGluR5d receptor at 40X 10⁴Cells/well were seeded in poly-L-lysine coated 24-well plates in culture medium containing 1. mu. Ci/well [3H ]]Inositol. The cells were cultured overnight (16h) and then washed 3 times at 37 ℃ in HEPPS buffered saline (146mM NaCl, 4.2mM KCl, 0.5mM MgCl) supplemented with 1 unit/ml pyruvate glutamine transaminase and 2mM pyruvate₂0.1% glucose, 20mM HEPES, pH 7.4) for 1 hour. Cells were washed once with HEPES buffered saline and then pre-incubated in HEPES buffered saline containing 10mM LiCl for 10 minutes. The compound (agonist) was added and incubated at 37 ℃ for 30 minutes. By pre-incubation of the test compounds for 15 minutes followed by incubation for 30 minutes in the presence of glutamate (80. mu.M) or DHPG (30. mu.M)Determining antagonist activity. The reaction was terminated by adding 0.5ml perchloric acid (5%) on ice and incubating at 4 ℃ for at least 30 minutes. Samples were collected in 15ml Falcon tubes and inositol triphosphate was isolated using a Dowex column as described below.

[1420] Inositol triphosphate measurement using gravity-fed ion exchange column

[1421] Preparation of ion-exchange column

[1422] The ion exchange resin (Dowex AG1-X8 formate form, 200-400 mesh, BIORAD) was washed three times with distilled water and stored at 4 ℃. 1.6ml of resin was added to each column and washed with 3ml of 2.5mM HEPES, 0.5mM EDTA, pH7.4.

[1423] Sample processing

[1424] Samples were collected in 15ml Falcon tubes and neutralized with 0.375M HEPES, 0.75M KOH. Potassium perchlorate was precipitated by addition of 4ml HEPES/EDTA (2.5/0.5mM, pH 7.4). The supernatant was applied to a prepared Dowex column.

[1425] Isolation of inositol triphosphate

[1426] Glycerol phosphatidylinositol was eluted with 8ml 30mM ammonium formate

[1427] Total triphosphoinositol was eluted with 8ml 700mM ammonium formate/100 mM formic acid and the eluate was collected in scintillation vials. The eluate mixed with 8ml of flash was counted.

[14281 Screening for Activity against tresr Compounds。

[1429] Adult Labrador retrievers of both genders were used and trained to stand in a Pavlov string bag. A muco-to-cutaneous esophagostomi was formed and the dogs were allowed to recover completely before any trials were performed.

[1430] Measurement of motility

[1431] Briefly, gastric, sub-esophageal sphincter (LES) and esophageal pressure were measured by introducing a multi-lumen tap/side hole device (Dentsleeve, Adelaide, South Australia) via an esophageal ostomy after approximately 17 hours of fasting and free water supply. The device was perfused with water using a low-compatibility pressure perfusion pump (Dentsleeve, Adelaide, SouthAustralia). The air perfusion tube measures swallowing in the oral direction and the pH is monitored on the LES with a 3cm antimony electrode. All signals were amplified and acquired at 10Hz from a personal computer.

[1432] When baseline measurements of gastric/LESIII phase locomotor activity without fasting were obtained, placebo (0.9% NaCl) or test compound was administered intravenously (i.v., 0.5ml/kg) in the forelimb vein. After 10 minutes of intravenous administration, a nutritional meal (10% peptone, 5% D-glucose, 5% fat emulsion, pH 3.0) was gavaged at 100 ml/min through the central lumen of the device to a final volume of 30 ml/kg. Perfusing nutrient meals air was perfused at 500 ml/min until gastric pressures of 10 + -1 mmHg were obtained. An infusion pump was used to further air infuse or vent air from the stomach, keeping the pressure at this level throughout the experiment. The test time from the start time of nutrient infusion to the end of air infusion was 45 minutes. This approach has been identified as a means to motivate the reliability of TLESRs.

[1433] TLESRs are defined as a decrease in the subdophageal sphincter (meaning the pressure inside the stomach) at a rate of > 1 mmHg/s. Before its onset, its remission should not precede pharyngeal signaling by ≦ 2s, in which case remission is classified as swallowing-induced. The pressure difference between LES and stomach should be LESs than 2mmHg and the duration of complete remission is greater than 1 s.

[1434] Abbreviations

BSA bovine serum albumin

CCD electrode coupling device

CRC concentration response curve

DHPG 3, 5-dihydroxyphenylglycine

EDTA ethylene diamine tetraacetic acid

FLIPR fluorescence image plate reader

GHEK human embryonic kidney containing GLAST

GLAST glutamate/aspartate transporters

HEPES 4- (2-hydroxyethyl) -1-piperazineethanesulfonic acid (buffer)

IP3 inositol triphosphate

[1435] Results

[1436]Typical IC measured in the test described above₅₀The value is 10. mu.M or less. In one aspect of the invention, an IC₅₀Less than 2. mu.M. In another aspect of the invention, an IC₅₀Less than 0.2. mu.M. In another aspect of the invention, an IC₅₀Less than 0.05. mu.M.

Claims

1. A compound, or pharmaceutically acceptable salt thereof, selected from the compounds listed in the following table:

2. a pharmaceutical formulation comprising as active ingredient a therapeutically effective amount of a compound according to claim 1 in association with one or more pharmaceutically acceptable diluents, excipients and/or inert carriers.

3. A pharmaceutical formulation according to claim 2, for use in the prevention and/or treatment of mGluR5 receptor mediated disorders.

4. A compound according to claim 1 for use in therapy.

5. A compound according to claim 1 for use in the prevention and/or treatment of mGluR5 receptor mediated disorders.

6. The compound according to claim 5, wherein the disorder is a neurological disorder.

7. The compound according to claim 5, wherein the disorder is a psychiatric disorder.

8. The compound according to claim 5, wherein the condition is selected from chronic and acute pain conditions.

9. The compound according to claim 5, wherein the disorder is a gastrointestinal disorder.

10. The compound according to claim 5, wherein the disorder is selected from the group consisting of Alzheimer's disease, senile dementia, AIDS-induced dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's chorea, migraine, epilepsy, schizophrenia, depression, anxiety, acute anxiety, obsessive compulsive disorder, ocular disorders, diabetic retinopathy, glaucoma, auditory neurological disorders, chemotherapy-induced neuropathy, postherpetic neuralgia and trigeminal neuralgia, tolerance, dependence, addiction and craving disorders, neurodevelopmental disorders, autism, mental retardation, schizophrenia, Down's syndrome, pain associated with migraine, inflammatory pain, neuropathic pain disorders, arthritis and rheumatosis, low back pain, post-operative pain, pain associated with angina, renal and biliary colic, menstruation, migraine gout, stroke, post-operative pain, pain associated with angina, head trauma, hypoxic and ischemic injury, hypoglycemia, cardiovascular disease, GERD, and epilepsy.

11. Use of a compound according to claim 1 in the manufacture of a medicament for the prevention and/or treatment of mGluR5 receptor mediated disorders.

12. A method for the prevention and/or treatment of mGluR5 receptor-mediated disorders comprising administering to a mammal in need of such prevention and/or treatment a therapeutically effective amount of a compound according to claim 1.

13. The method according to claim 12, wherein the disorder is a neurological disorder.

14. The method according to claim 12, wherein the disorder is a psychiatric disorder.

15. The method according to claim 12, wherein the condition is selected from chronic and acute pain conditions.

16. The method according to claim 12, wherein the disorder is a gastrointestinal disorder.

17. The method according to claim 12, wherein the disorder is selected from the group consisting of alzheimer's disease, senile dementia, AIDS-induced dementia, parkinson's disease, amyotrophic lateral sclerosis, huntington's chorea, migraine, epilepsy, schizophrenia, depression, anxiety, acute anxiety, obsessive compulsive disorder, ocular disorders, diabetic retinopathy, glaucoma, auditory neurological disorders, chemotherapy-induced neuropathy, post herpetic neuralgia and trigeminal neuralgia, tolerance, dependence, addiction and craving diseases, neurodevelopmental disorders, autism, mental retardation, schizophrenia, down's syndrome, pain associated with migraine, inflammatory pain, neuropathic pain disorders, arthritis and rheumatosis, low back pain, post-operative pain, pain associated with angina, renal and biliary colic, menstruation, migraine gout, stroke, post-operative pain, pain associated with angina, and pain associated with angina, Head trauma, hypoxic and ischemic injury, hypoglycemia, cardiovascular disease, and epilepsy.

18. A method of inhibiting the activity of mGluR5 receptor comprising treating a cell containing said receptor with an effective amount of a compound according to claim 1.