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CN1761464A - Substituted p-diaminobenzene derivatives - Google Patents

Substituted p-diaminobenzene derivatives Download PDF

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CN1761464A
CN1761464A CNA2004800075074A CN200480007507A CN1761464A CN 1761464 A CN1761464 A CN 1761464A CN A2004800075074 A CNA2004800075074 A CN A2004800075074A CN 200480007507 A CN200480007507 A CN 200480007507A CN 1761464 A CN1761464 A CN 1761464A
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chloro
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N·汉津
M·罗特莱恩德
A·里岑
W·P·沃特森
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    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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Abstract

本发明涉及通式I的苯胺衍生物或其可药用的盐以及其应用。

Figure 200480007507

This invention relates to aniline derivatives of general formula I or pharmaceutically acceptable salts thereof and their applications.

Figure 200480007507

Description

被取代的对-二氨基苯衍生物Substituted p-diaminobenzene derivatives

技术领域technical field

本发明涉及是KCNQ族钾离子通道开放剂的被取代的新型对-二氨基苯衍生物。该化合物可用于预防、治疗和抑制对KCNQ族钾离子通道的开放有响应的病症和疾病，一种该类疾病是癫痫。The present invention relates to novel substituted p-diaminobenzene derivatives which are potassium ion channel openers of the KCNQ family. The compounds are useful for the prevention, treatment and inhibition of conditions and diseases responsive to the opening of the KCNQ family of potassium ion channels, one such disease being epilepsy.

背景技术Background technique

离子通道是调节包括包括钾、钙、氯化物和钠在内的离子流入和流出细胞的细胞蛋白。该类通道存在于所有动物和人的细胞中并影响包括神经元传递、肌肉收缩、和细胞分泌在内的许多过程。Ion channels are cellular proteins that regulate the flow of ions, including potassium, calcium, chloride, and sodium, into and out of cells. Such channels are present in all animal and human cells and affect many processes including neuronal transmission, muscle contraction, and cellular secretion.

人类具有大约70多种编码钾通道子单元的基因(Jentsch NatureReviews Neuroscience 2000、1、21-30)，这些基因在结构和功能方面都具有很大的差异。在脑中发现的神经元钾通道主要负责维持负的静息膜电位以及负责控制动作电位后膜的复极化。Humans have more than 70 genes encoding potassium channel subunits (Jentsch Nature Reviews Neuroscience 2000, 1, 21-30), which vary greatly in structure and function. Neuronal potassium channels found in the brain are primarily responsible for maintaining a negative resting membrane potential and for controlling membrane repolarization following an action potential.

钾通道基因的一个子集是KCNQ族。已经表明五分之四KCNQ基因突变是包括心律失常、聋症和癫痫在内的一些疾病的基础(JentschNature Reviews Neuroscience 2000、1、21-30)。A subset of potassium channel genes is the KCNQ family. Four out of five KCNQ gene mutations have been shown to underlie several diseases including cardiac arrhythmias, deafness and epilepsy (Jentsch Nature Reviews Neuroscience 2000, 1, 21-30).

认为该KCNQ4基因编码在耳蜗外部毛细胞和前庭器官I型毛细胞中所发现的钾通道的分子联系，其突变可导致形成遗传性聋症。The KCNQ4 gene is thought to encode the molecular link to potassium channels found in the outer hair cells of the cochlea and type I hair cells of the vestibular organ, mutations of which can lead to the development of hereditary deafness.

KCNQ1(KvLQT1)与心脏中KCN1(最小的K(+)-通道蛋白)基因的产物一起装配形成心脏延迟整流器样K(+)电流。这种通道的突变可能造成一种形式的1型遗传性长QT综合征(LQT1)并且其与聋症的形成有关(RobbinsPharnzacolTlier 2001，90，1-19)。KCNQ1 (KvLQT1) assembles with the product of the KCN1 (minimal K(+)-channel protein) gene in the heart to form cardiac delayed rectifier-like K(+) currents. Mutations in this channel may cause a form of hereditary long QT syndrome type 1 (LQT1) and have been associated with the development of deafness (Robbins Pharnzacol Tlier 2001, 90, 1-19).

在1988年发现了基因KCNQ2和KCNQ3并表明其在被称为良性家族性新生儿惊厥的遗传形式的癫痫中产生变异(Rogawski Trends inNeurosciences 2000，23，393-398)。KCNQ2和KCNQ3基因所编码的蛋白局限于人与癫痫发作的产生和传播有关的脑区域——皮层和海马的锥体细胞中(Cooper等人，Proceedi77gs National Academy ofScie7zce U s A 2000，97，4914-4919)。The genes KCNQ2 and KCNQ3 were discovered in 1988 and shown to be mutated in an inherited form of epilepsy known as benign familial neonatal convulsions (Rogawski Trends in Neurosciences 2000, 23, 393-398). The proteins encoded by the KCNQ2 and KCNQ3 genes are restricted to the human brain regions involved in the generation and spread of epileptic seizures - in the pyramidal cells of the cortex and hippocampus (Cooper et al., Proceedi77gs National Academy of Scie7zce U s A 2000, 97, 4914- 4919).

KCNQ2和KCNQ3是当在体外被表达时形成“M-电流”的两种钾通道子单元。所说的M-电流是一种在许多类型的神经元细胞中发现的非-灭活的钾电流。在各细胞类型中，由于是引发动作电位范围中唯一持续的电流，所以其在控制膜兴奋性方面是显性的(Marrion AyanualReview Physiology 1997，59，483-504)。M-电流的调节对神经元兴奋性有显著作用，例如该电流的活化将降低神经元兴奋性。这些KCNQ通道的开放剂或M-电流的活化剂将降低神经元的过度活性并且因此可用于治疗、预防或抑制癫痫发作和特征为神经原活性过度的其它疾病和病症，如神经元兴奋性过度，包括惊厥性病症、癫痫和神经性疼痛。KCNQ2 and KCNQ3 are two potassium channel subunits that form "M-currents" when expressed in vitro. The M-current is a non-inactivating potassium current found in many types of neuronal cells. In each cell type, it is dominant in controlling membrane excitability as it is the only sustained current in the range of eliciting action potentials (Marrion Ayanual Review Physiology 1997, 59, 483-504). Modulation of the M-current has a pronounced effect on neuronal excitability, eg activation of this current will reduce neuronal excitability. Openers of these KCNQ channels or activators of M-currents will reduce neuronal hyperactivity and are therefore useful in the treatment, prevention or inhibition of epileptic seizures and other diseases and conditions characterized by neuronal hyperactivity, such as neuronal hyperexcitability , including convulsive disorders, epilepsy, and neuropathic pain.

在EP554543中公开了瑞替加滨(D-23129；N-(2-氨基-4-(4-氟苄基氨基)-苯基)氨基甲酸乙酯)以及其类似物。瑞替加滨是一种在体内和体外都具有广谱和强效抗惊厥性质的抗惊厥化合物。其在用大鼠和小鼠进行的一系列抗惊厥试验中和在基因动物模型——DBA/2小鼠模型中被口服和腹膜内给药后是有效的，所说的试验包括：电诱导的癫痫发作、戊四唑、木防己苦毒素和N-甲基-D-天冬氨酸酯(NMDA)诱导的癫痫发作(Rostock等人，Epilepsy Research 1996，23，211-223)。此外，瑞替加滨在复杂的部分发作的扁桃体兴奋模型中也是有效的。在临床试验中，最近已经表明瑞替加滨可有效降低癫痫患者癫痫发作的发生率(Bialer等人，Epilepsy Research 2002，51，31-71)。Retigabine (D-23129; ethyl N-(2-amino-4-(4-fluorobenzylamino)-phenyl)carbamate) and analogs thereof are disclosed in EP554543. Retigabine is an anticonvulsant compound with broad-spectrum and potent anticonvulsant properties both in vivo and in vitro. It was effective in a series of anticonvulsant tests in rats and mice and after oral and intraperitoneal administration in a genetic animal model, the DBA/2 mouse model, including: electrically induced Seizures induced by pentylenetetrazol, tetrantoxin and N-methyl-D-aspartate (NMDA) (Rostock et al., Epilepsy Research 1996, 23, 211-223). In addition, retigabine was also effective in a complex model of partial-onset amygdala excitation. In clinical trials, retigabine has recently been shown to be effective in reducing the incidence of seizures in epileptic patients (Bialer et al., Epilepsy Research 2002, 51, 31-71).

已经表明瑞替加滨活化了神经元细胞中的K(+)电流神经元并且被诱导的这种电流的药理学与所公布的M-通道的药理学表现一致，其目前与KCNQ2/3K(+)通道杂多聚体有关。这表明KCNQ2/3通道的活化可能是这种物质有一些抗惊厥活性的原因(Wiclcenden等人，MolecularPharmacology 2000，58，591-600)-并且通过相似机理起作用的其它物质可能具有相似的应用。Retigabine has been shown to activate K(+) currents in neuronal cells and the pharmacology of this induced current is consistent with the published pharmacology of M-channels, which are currently associated with KCNQ2/3K( +) related to channel heteromultimers. This suggests that activation of KCNQ2/3 channels may be responsible for some anticonvulsant activity of this substance (Wiclcenden et al., Molecular Pharmacology 2000, 58, 591-600) - and that other substances acting by similar mechanisms may have similar applications.

还已经报道了KCNQ 2和3通道在神经性疼痛模型中被上调(Wickenden等人，Society for Neuroscience Abstracts 2002，454.7)，并且已经假设钾通道调节剂在神经性疼痛和癫痫中都有效(Schroder等人，Neuropharmacology 2001，40，888-898)。KCNQ 2 and 3 channels have also been reported to be upregulated in models of neuropathic pain (Wickenden et al., Society for Neuroscience Abstracts 2002, 454.7), and potassium channel modulators have been postulated to be effective in both neuropathic pain and epilepsy (Schroder et al. People, Neuropharmacology 2001, 40, 888-898).

还已经表明瑞替加滨在神经性疼痛动物模型中是有益的(Blackbum-Munro和Jensen European Journal of Pharmacology2003，460，109-116)，并且因此暗示KCNQ通道开放剂将可用于治疗包括神经性疼痛在内的疼痛病症。Retigabine has also been shown to be beneficial in animal models of neuropathic pain (Blackbum-Munro and Jensen European Journal of Pharmacology 2003, 460, 109-116), and it is thus suggested that KCNQ channel openers will be useful in the treatment of neuropathic pain including Pain disorders included.

据报道，KCNQ通道mRNA局限于脑和与疼痛有关的其它中枢神经系统区域中(Goldstein等人，Society for Neuroscienee Abstracts2003，53.8)。KCNQ channel mRNA has been reported to be localized in the brain and other central nervous system regions involved in pain (Goldstein et al., Society for Neuroscienee Abstracts 2003, 53.8).

除在神经性疼痛中的作用外，KCNQ 2-5的mRNA在三叉神经和背根神经节以及在三叉神经核尾部中的表达意味着这些通道的开放剂还可以影响偏头痛性疼痛的感觉处理(Goldstein等人，Society forNeuroscienceAbstracts 2003，53.8)。In addition to its role in neuropathic pain, KCNQ 2-5 mRNA expression in the trigeminal and dorsal root ganglia and in the caudal trigeminal nucleus implies that openers of these channels may also affect sensory processing of migrainous pain (Goldstein et al., Society for Neuroscience Abstracts 2003, 53.8).

最新报道证明除KCNQ2的mRNA外，在星形胶质细胞和神经胶质细胞中还表达KCNQ3和5的mRNA。因此，KCNQ 2、3和5通道可帮助调节CNS中的突触活性并有助于KCNQ通道开放剂的神经保护作用(Noda等人，Society for Neuroscience Abstracts 2003，53.9)。Recent reports demonstrate that in addition to KCNQ2 mRNA, KCNQ3 and 5 mRNA are also expressed in astrocytes and glial cells. Thus, KCNQ 2, 3 and 5 channels may help regulate synaptic activity in the CNS and contribute to the neuroprotective effects of KCNQ channel openers (Noda et al., Society for Neuroscience Abstracts 2003, 53.9).

因为已经表明瑞替加滨可预防大鼠红藻氨酸诱导的癫痫状态后缘神经变性和细胞凋亡标记的表达，因此，瑞替加滨和其它KCNQ调节剂可表现出保护不出现癫痫的神经变性方面情况的作用(Ebert等人，Epilepsia 2002，43 Suppl 5，86-95)。其与预防患者癫痫的进程有关，即是抗-致癫痫的。还已经表明瑞替加滨延迟了另一种癫痫发展模型——大鼠海马兴奋的进程(Tober等人，European Journal OfPharmacology 1996，303，163-169)。Because retigabine has been shown to prevent kainic acid-induced posterior limb neurodegeneration and expression of apoptotic markers in the rat state of epilepsy, retigabine and other KCNQ modulators may therefore appear to protect against the development of epilepsy. Role of conditions in neurodegeneration (Ebert et al., Epilepsia 2002, 43 Suppl 5, 86-95). It is associated with preventing the progression of epilepsy in patients, ie is anti-epileptic. Retigabine has also been shown to delay the progression of hippocampal excitation in another model of epilepsy development, the rat (Tober et al., European Journal Of Pharmacology 1996, 303, 163-169).

因此，表明瑞替加滨和其它KCNQ调节剂的这些性质可防止神经元过度活化所诱导的神经元损害，并且可用于治疗神经变性疾病、和缓解癫痫患者的疾病(或是抗致癫痫的)。Therefore, it is suggested that these properties of retigabine and other KCNQ modulators may prevent neuronal damage induced by neuronal hyperactivation and may be useful for the treatment of neurodegenerative diseases, and for the alleviation of disease in epileptic patients (or anti-epileptic) .

已知在临床中用抗惊厥化合物如苯并二氮杂_类和氯甲噻唑来治疗酒精戒断综合征并且已知其它抗惊厥化合物例如加巴喷丁在这种综合征的动物模型中十分有效(Watson等人，Neuropharmacology1997，36，1369-1375)，因此，预期其它抗惊厥化合物如KCNQ开放剂在这种情况中是有效的。Alcohol withdrawal syndrome is known to be treated clinically with anticonvulsant compounds such as benzodiazepines and clomethiazole and other anticonvulsant compounds such as gabapentin are known to be very effective in animal models of this syndrome (Watson et al., Neuropharmacology 1997, 36, 1369-1375), therefore, other anticonvulsant compounds such as KCNQ openers are expected to be effective in this situation.

在与焦虑和情感行为如双相型障碍有关的脑区域例如海马和扁桃体中发现了KCNQ 2和3子单元的mRNA(Saganich等人，Journal ofNeuroscience 2001，21，4609-4624)，据报道，瑞替加滨在一些焦虑样行为动物模型中是有效的(Hartz等人，Journal ofPsychopharmacology 2003，17 suppl 3，A28，B16)，并且在双相型障碍的治疗中使用了临床所用的其它抗惊厥化合物。mRNAs for KCNQ 2 and 3 subunits have been found in brain regions associated with anxiety and affective behavior such as bipolar disorder, such as the hippocampus and amygdala (Saganich et al., Journal of Neuroscience 2001, 21, 4609-4624), it has been reported that Rui Tigabine is effective in some animal models of anxiety-like behavior (Hartz et al., Journal of Psychopharmacology 2003, 17 suppl 3, A28, B16), and other anticonvulsant compounds used clinically in the treatment of bipolar disorder .

WO 200196540公开了通过表达KCNQ2和KCNQ3基因所形成的M-电流的调节剂用于失眠症的应用，而WO 2001092526公开了可以用KCNQ5调节剂来治疗睡眠病症。WO 200196540 discloses the use of regulators of M-current formed by expressing KCNQ2 and KCNQ3 genes for insomnia, while WO 2001092526 discloses that KCNQ5 regulators can be used to treat sleep disorders.

WO01/022953描述了瑞替加滨用于预防和治疗神经性疼痛如异常性疼痛、痛觉过敏性疼痛、幻痛、与糖尿病性神经病有关的神经性疼痛和与偏头痛有关的神经性疼痛的应用。WO01/022953 describes the use of retigabine for the prevention and treatment of neuropathic pain such as allodynia, hyperalgesia, phantom pain, neuropathic pain associated with diabetic neuropathy and neuropathic pain associated with migraine .

WO02/049628描述了瑞替加滨用于预防、治疗、抑制和改善焦虑障碍如焦虑、泛化性焦虑症、恐慌性焦虑、强迫症、社交恐怖症、行为性焦虑(pefformance anxiety)、创伤后精神紧张性障碍、急性应激反应、适应性障碍、疑病障碍、离别焦虑障碍、广场恐怖症和特异恐怖的应用。WO02/049628 describes the use of retigabine for the prevention, treatment, suppression and improvement of anxiety disorders such as anxiety, generalized anxiety disorder, panic anxiety, obsessive-compulsive disorder, social phobia, behavioral anxiety (pefformance anxiety), post-traumatic Application in tension disorder, acute stress response, adjustment disorder, hypochondria, separation anxiety disorder, agoraphobia and specific phobia.

WO97/15300描述了瑞替加滨用于治疗神经变性病症如阿耳茨海默氏病；亨廷顿舞蹈病；硬化症如多发性硬化和肌萎缩性侧索硬化；Creutzfeld-Jalcob病；帕金森氏病；AIDS或风疹病毒、疱疹病毒、包柔氏螺旋体属和未知的病原体感染诱导的脑病；创伤诱导的神经变性；神经元兴奋过度状态如在药物戒断或中毒中的状态；外周神经系统的神经变性疾病如多神经病和多神经炎(polyneuritides)的应用。WO97/15300 describes retigabine for the treatment of neurodegenerative disorders such as Alzheimer's disease; Huntington's disease; sclerosis such as multiple sclerosis and amyotrophic lateral sclerosis; Creutzfeld-Jalcob disease; Parkinson's encephalopathy induced by infection with AIDS or rubella virus, herpes virus, Borrelia, and unknown pathogens; trauma-induced neurodegeneration; neuronal hyperexcitability states such as those in drug withdrawal or intoxication; peripheral nervous system Use in neurodegenerative diseases such as polyneuropathy and polyneuritis (polyneuritis).

因此，十分需要是有效的KCNQ族钾通道开放剂的新化合物。Accordingly, there is a great need for new compounds that are potent KCNQ family potassium channel openers.

还需要相对于已知的是KCNQ族钾通道开放剂的化合物，如瑞替加滨而言具有改善的性质的新化合物。希望对一种或多种下面的参数进行改善：半衰期、清除率、选择性、与其它药物治疗的相互作用、生物利用度、效力、配制性(formulability)、化学稳定性、代谢稳定性、膜渗透性、溶解度和治疗指数。该类参数的改善可导致诸如下面方面的改善：There is also a need for new compounds with improved properties relative to compounds known to be KCNQ family potassium channel openers, such as retigabine. It is desirable to improve one or more of the following parameters: half-life, clearance, selectivity, interaction with other drug treatments, bioavailability, potency, formulability, chemical stability, metabolic stability, membrane Permeability, Solubility and Therapeutic Index. Improvements in such parameters can lead to improvements such as:

○通过降低一天所需剂量的数目而改善给药方案，○ improving the dosing regimen by reducing the number of doses required in a day,

○易于将许多药物给药于患者，○ Ease of administering many drugs to patients,

●降低副作用，●Reduce side effects,

●扩大治疗指数，● Expanded therapeutic index,

●改善耐受性或●Improved tolerance or

●改善顺从性。● Improve compliance.

本发明的概述Summary of the invention

本发明的一个目的是提供是有效的KCNQ族钾通道开放剂的新型化合物。It is an object of the present invention to provide novel compounds that are potent KCNQ family potassium channel openers.

本发明的化合物是通式I的被取代的苯胺衍生物或其盐The compound of the present invention is a substituted aniline derivative of general formula I or a salt thereof

其中Y、U、X、Z、s、q、R1、R2和R3的定义如下所述。Wherein Y, U, X, Z, s, q, R 1 , R 2 and R 3 are defined as follows.

本发明还涉及包含一种或多种式I的化合物的药物组合物以及其应用。The present invention also relates to pharmaceutical compositions comprising one or more compounds of formula I and uses thereof.

本发明的详细描述Detailed description of the invention

因此，本发明涉及通式I的被取代的对-二氨基苯衍生物或其盐Therefore, the present invention relates to substituted p-diaminobenzene derivatives of general formula I or salts thereof

其中s是0或1；where s is 0 or 1;

U是O、S、SO2、SO2NR11、CO-O或CO-NR11；其中U is O, S, SO 2 , SO 2 NR 11 , CO-O or CO-NR 11 ; where

R11选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基；或R 11 is selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl; or

R2和R11和其与之相连的氮原子一起形成一种任选地包含1、2或3个另外的杂原子的5-8员饱和或不饱和的环；R and R together with the nitrogen atom to which they are attached form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms;

q是0或1；q is 0 or 1;

X是CO或SO2；前提是当X是SO2时q是0；X is CO or SO2 ; provided that q is 0 when X is SO2 ;

Z是O或S；Z is O or S;

R1选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、酰基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基和氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基；R 1 is selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(alkene/alkyne)yl, acyl, hydroxy-C 1-6 -alk(alkene/alkynyl)yl, hydroxy-C 3-8 -cycloalkane(en)yl, hydroxy-C 3-8 - Cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl, halo-C 3-8 -cycloalkane( Alken)yl, Halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Cyano-C 1-6 -alk(alkene/alkyne) cyano-C 3-8 -cycloalk(en)yl and cyano-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl;

R2选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、酰基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤素、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基、氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、NR10R10′-C1-6-烷(链烯/炔)基、NR10R10′-C3-8-环烷(链烯)基和NR10R10′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基；R 2 is selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -Alk(en/alkyn)yl, Ar, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3-8 -cycloalk(en)yl, Ar-C 3-8- Cycloalk(en)yl-C 1-6 -alk(alkene/alkyn)yl, acyl, hydroxy-C 1-6 -alk(en/alkyn)yl, hydroxy-C 3-8 -cycloalkane( Alken) group, hydroxy-C 3-8 -cycloalk(en) group-C 1-6 -alk(alkene/alkynyl) group, halogen, halo-C 1-6 -alk(alkene/alkyne) group ) group, halo-C 3-8 -cycloalk(alkene) group, halo-C 3-8 -cycloalk(alkene) group-C 1-6 -alk(alkene/alkyne) group, cyanide Cyano-C 1-6 -alk(en/alkyn)yl, cyano-C 3-8 -cycloalk(en)yl, cyano-C 3-8 -cycloalk(en)yl -C 1-6 -alk(en/alkyn)yl, NR 10 R 10′ -C 1-6 -alk(en/alkyn)yl, NR 10 R 10′ -C 3-8 -cycloalkane(alkynyl) alken)yl and NR 10 R 10′ -C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl;

其中R10和R10′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基和氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基，或wherein R 10 and R 10′ are independently selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl ) group-C 1-6 -alk(alkene/alkyne)yl, hydroxyl-C 1-6 -alk(alkene/alkynyl)yl, hydroxyl-C 3-8 -cycloalkane(alkene)yl, hydroxyl- C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl, halo-C 3- 8 -cycloalk(en)yl, halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, cyano-C 1-6 -alk( Alken/alkynyl), cyano-C 3-8 -cycloalkan(en)yl and cyano-C 3-8 -cycloalk(en)yl-C 1-6 -alk(alken/alkyne ) base, or

R10和R10′和其与之相连的氮原子一起形成一种任选地包含1、2或3个另外的杂原子的5-8员饱和或不饱和的环；R 10 and R 10' together with the nitrogen atom to which they are attached form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms;

前提是当R2是卤素或氰基是，s是0；和provided that when R2 is halogen or cyano, s is 0; and

前提是当s是1和R2是氢原子或酰基时U是O或S；provided that U is O or S when s is 1 and R2 is a hydrogen atom or an acyl group;

R3选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、杂环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、C1-6-烷(链烯/炔)基-杂环烷(链烯)基、杂环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-杂环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、Ar-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)氧基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-C3-8-环烷(链烯)基、C1-6-烷(链烯/炔)氧基-杂环烷(链烯)基、Ar-氧基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)氧基-羰基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-杂环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、羟基-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、羟基-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-杂环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基-Ar、卤代-C3-8-环烷(链烯)基-Ar、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基-Ar、卤代-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基-Ar、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基、氰基-杂环烷(链烯)基、氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、氰基C1-6-烷(链烯/炔)基-杂环烷(链烯)基、酰基-C1-6-烷(链烯/炔)基、酰基-C3-8-环烷(链烯)基、酰基-杂环烷(链烯)基、酰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、酰基-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、酰基-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、NR12R12′、任选地被取代的NR12R12′-C1-6-烷(链烯/炔)基、任选地被取代的NR12R12′-C3-8-环烷(链烯)基、任选地被取代的NR12R12′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基；其中R 3 is selected from C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, heterocycloalk(en)yl, C 3-8 -cycloalk(en)yl ) group-C 1-6 -alk(en/alkyn)yl, C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(en)yl, C 1-6 -alk (Alken/Alkyn)yl-Heterocycloalkan(en)yl, Heterocycloalkan(en)yl-C 1-6 -Alk(alken/Alkyn)yl, Ar, Ar-C 1-6 -Alkane (alkene/alkyn)yl, Ar-C 3-8 -cycloalk(en)yl, Ar-heterocycloalk(en)yl, Ar-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Ar-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(en)yl, Ar-C 1-6 -alk (Alken/Alkyn)yl-Heterocycloalkan(alkene)yl, C 1-6 -Alk(alkene/Alkyn)oxy-C 1-6 -Alk(alkene/Alkyn)yl, C 3-8 -Cycloalk(alkene)oxy-C 1-6 -alk(en/alkyn)yl, C 1-6 -alk(en/alkyn)oxy-C 3-8 -cycloalk(alkene) Base, C 1-6 -alk(alkene/alkynyl)oxy-heterocycloalkane(en)yl, Ar-oxy-C 1-6 -alk(en/alkynyl)yl, Ar-C 1- 6 -alk(alkene/alkyne)oxy-C 1-6 -alk(en/alkyn)yl, C 1-6 -alk(alkene/alkyne)oxy-carbonyl-C 1-6 -alk( Alken/alkynyl) group, C 3-8 -cycloalk(en)oxy-carbonyl-C 1-6 -alk(en/alkyn) group, C 3-8 -cycloalk(en)yl- C 1-6 -alk(alkene/alkynyl)oxy-carbonyl-C 1-6 -alk(en/alkynyl)yl, hydroxy-C 1-6 -alk(en/alkynyl)yl, hydroxy-C 3-8 -Cycloalkane(alkene)yl, Hydroxy-Heterocycloalkane(alkene)yl, Hydroxy-C 3-8 -Cycloalkane(alkene)yl-C 1-6 -alk(alkene/alkyne) Hydroxy-C 1-6 -alk(en/yn)yl-C 3-8 -cycloalk(en)yl, Hydroxy-C 1-6 -alk(en/yn)yl-heterocycloalkane (Alken)yl, Halo-C 1-6 -alk(en/alkyn)yl, Halo-C 3-8 -cycloalk(alken)yl, Halo-heterocycloalk(en)yl , Halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Halo-C 1-6 -alk(en/alkyn)yl-C 3 -8 -cycloalk(alkene)yl, halo-C 1-6 -alk(en/alkyn)yl-heterocycloalk(en)yl, halo-C 1-6 -alk(alkene/alkyn) Alkyn) base-Ar, halo-C 3-8 -cycloalk(en) base-Ar, halo-C 3-8 -cycloalk(en) base-C 1-6 -alk(alkene/ Alkynyl-Ar, Halo-C 1-6 -alk(alkene/alkyn)yl-C 3-8 -cycloalk(en)yl-Ar, Cyano-C 1-6 -alk(alkene) /Alkynyl) group, cyano-C 3-8 -cycloalkane (alkene) group, cyano-heterocycloalkane (alkene) group, cyano-C 3-8 -cycloalkane (alkene) group-C 1-6 -alk(en/alkyn)yl, cyano-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(en)yl, cyanoC 1-6- Alk(alken/alkyn)yl-heterocycloalkan(en)yl, acyl-C 1-6 -alk(alken/alkyn)yl, acyl-C 3-8 -cycloalk(en)yl, acyl -Heterocycloalkan(en)yl, acyl-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, acyl-C 1-6 -alk(alken) /alkyn)yl-C 3-8 -cycloalk(en)yl, acyl-C 1-6 -alk(en/alkyn)yl-heterocycloalk(en)yl, NR 12 R 12′ , any Optionally substituted NR 12 R 12′ -C 1-6 -alk(alkene/alkyn)yl, optionally substituted NR 12 R 12′ -C 3-8 -cycloalk(en)yl, Optionally substituted NR 12 R 12′ -C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl; wherein

R12和R12′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-杂环烷(链烯)基、Ar-氧基-C1-6-烷(链烯/炔)基、Ar-氧基-C3-8-环烷(链烯)基、Ar-氧基C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-氧基-杂环烷(链烯)基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基和氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基，或R 12 and R 12′ are independently selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl Base-C 1-6 -alk(en/alkyn)yl, Ar, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3-8 -cycloalk(en)yl, Ar -C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Ar-heterocycloalk(en)yl, Ar-oxy-C 1-6 -alk (alkene/alkynyl) group, Ar-oxyl-C 3-8 -cycloalk(en)yl, Ar-oxyl C 3-8 -cycloalk(en)yl-C 1-6 -alk( Alken/Alkyn)yl, Ar-Oxy-Heterocycloalkane(alkene)yl, Hydroxy-C 1-6 -Alk(alkene/Alkyn)yl, Hydroxy-C 3-8 -Cycloalkane(alkene)yl Hydroxy-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl, halo -C 3-8 -cycloalk(en)yl, halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, cyano-C 1- 6 -alk(en/alkyn)yl, cyano-C 3-8 -cycloalk(en)yl and cyano-C 3-8 -cycloalk(en)yl-C 1-6 -alk( alkenyl/alkynyl) group, or

R12和R12′和其与之相连的氮原子一起形成一种任选地包含1、2或3个另外的杂原子的5-8员饱和或不饱和的环；R 12 and R 12' together with the nitrogen atom to which they are attached form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms;

前提是当R3是NR12R12′时，q是0；The premise is that when R 3 is NR 12 R 12′ , q is 0;

和and

Y表示式XXIV、XXV、XXVI、XXVII、XXVIII、XXXXI或XXXXII的基团：Y represents a group of formula XXIV, XXV, XXVI, XXVII, XXVIII, XXXXI or XXXXII:

Figure A20048000750700281
Figure A20048000750700281

或or

Figure A20048000750700282
Figure A20048000750700282

其中in

该线表示一种将Y所示的基团连接到该碳原子上的键；The line represents a bond connecting the group represented by Y to the carbon atom;

W是O或S；W is O or S;

V是N、C或CH；V is N, C or CH;

T是N、NH或O；T is N, NH or O;

a是0、1、2或3；a is 0, 1, 2 or 3;

b是0、1、2、3或4；b is 0, 1, 2, 3 or 4;

c是0或1；c is 0 or 1;

d是0、1、2或3；d is 0, 1, 2 or 3;

e是0、1或2；e is 0, 1 or 2;

f是0、1、2、3、4或5；f is 0, 1, 2, 3, 4 or 5;

g是0、1、2、3或4；g is 0, 1, 2, 3 or 4;

h是0、1、2或3；h is 0, 1, 2 or 3;

j是0、1或2；j is 0, 1 or 2;

k是0、1、2或3；和k is 0, 1, 2 or 3; and

各R5独立地选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-氧基、Ar-氧基-C1-6-烷(链烯/炔)基、Ar-氧基-C3-8-环烷(链烯)基、C1-6-烷(链烯/炔)基-杂环烷(链烯)基、Ar-氧基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、酰基、C1-6-烷(链烯/炔)氧基、C3-8-环烷(链烯)氧基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)氧基、C1-6-烷(链烯/炔)氧基羰基、卤素、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、-CO-NR6R6′、氰基、氰基-C1-6-烷(链烯/炔)基、氰基C3-8-环烷(链烯)基、氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、NR7R7′、S-R8和SO2R8，或者Each R 5 is independently selected from C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1- 6 -alk(en/alkyn)yl, Ar, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3-8 -cycloalk(en)yl, Ar-C 3-8 -Cycloalk(en)yl-C 1-6 -alk(alken/yn)yl, Ar-oxyl, Ar-oxy-C 1-6 -alk(alken/yn)yl, Ar-oxy Base-C 3-8 -cycloalk(en)yl, C 1-6 -alk(en/alkyn)yl-heterocycloalk(en)yl, Ar-oxy-C 3-8 -cycloalkane (Alken)yl-C 1-6 -alk(en/alkyn)yl, acyl, C 1-6 -alk(en/alkyn)oxy, C 3-8 -cycloalk(en)oxy , C 3-8 -cycloalk(en)yl-C 1-6 -alk(alkene/alkyne)oxy, C 1-6 -alk(alkene/alkyne)oxycarbonyl, halogen, halo- C 1-6 -alk(en/alkyn)yl, halo-C 3-8 -cycloalk(en)yl, halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, -CO-NR 6 R 6′ , cyano, cyano-C 1-6 -alk(en/alkyn)yl, cyanoC 3-8 -cycloalkane(chain alken)yl, cyano-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, NR 7 R 7′ , SR 8 and SO 2 R 8 , or

两个毗邻的R5与该芳族基团一起形成一种包含一个或两个杂原子的5-8员环；Two adjacent R 5 together with the aromatic group form a 5-8 membered ring containing one or two heteroatoms;

R6和R6′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基和Ar；R 6 and R 6′ are independently selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl -C 1-6 -alk(alkene/alkyn)yl and Ar;

R7和R7′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar、杂环烷(链烯)基-C1-6-烷(链烯/炔)基、杂环烷(链烯)基-C3-8-环烷(链烯)基、杂环烷(链烯)基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、杂环烷(链烯)基-Ar和酰基；或R 7 and R 7′ are independently selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl Base-C 1-6 -alk(alkene/alkyn)yl, Ar, heterocycloalkane(en)yl-C 1-6 -alk(en/alkyn)yl, heterocycloalkane(en)yl- C 3-8 -cycloalk(en)yl, heterocycloalk(en)yl-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl, hetero Cycloalk(en)yl-Ar and acyl; or

R7和R7′与该氮原子一起形成一种任选地包含1、2或3个另外的杂原子的5-8员饱和或不饱和的环；和R and R together with the nitrogen atom form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; and

R8选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar和-NR9R9′；其中R 8 is selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Ar and -NR 9 R 9' ; where

R9和R9′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基和C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基。R 9 and R 9′ are independently selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl and C 3-8 -cycloalk(en)yl -C 1-6 -alk(en/alkyn)yl.

在本发明的一个实施方案中，本发明涉及其中s是1的式I的化合物。In one embodiment of the invention, the invention relates to compounds of formula I wherein s is 1 .

在本发明的另一个实施方案中，本发明涉及其中s是0的式I的化合物。In another embodiment of the present invention, the present invention relates to compounds of formula I wherein s is 0.

在本发明的另一个实施方案中，本发明涉及其中s是1和U是O的式I的化合物。In another embodiment of the present invention, the present invention relates to compounds of formula I, wherein s is 1 and U is O.

在本发明的另一个实施方案中，本发明涉及其中s是1和U是S的式I的化合物。The present invention relates to compounds of formula I wherein s is 1 and U is S in another embodiment of the present invention.

在本发明的另一个实施方案中，本发明涉及其中s是1和U是SO2的式I的化合物。In another embodiment of the present invention, the present invention relates to compounds of formula I, wherein s is 1 and U is SO2 .

在另一个实施方案中，本发明涉及其中s是1和U是SO2NR11的式I的化合物。在该类化合物中，SO2NR11的硫原子被连接到式I的苯环上，而氮原子被连接到R2上。In another embodiment, the invention relates to compounds of formula I, wherein s is 1 and U is SO 2 NR 11 . In this type of compound, the sulfur atom of SO 2 NR 11 is connected to the benzene ring of formula I, and the nitrogen atom is connected to R 2 .

在另一个实施方案中，本发明涉及其中s是1和U是CO-O的式I的化合物。在该类化合物中，CO-O的羰基被连接到式I的苯环，而氧原子被连接到R2上。In another embodiment, the invention relates to compounds of formula I, wherein s is 1 and U is CO-O. In this class of compounds, the carbonyl group of CO-O is attached to the benzene ring of formula I, while the oxygen atom is attached to R2 .

在另一个实施方案中，本发明涉及其中s是1和U是CO-NR11的式I的化合物。在该类化合物中，CO-NR11的羰基被连接到式I的苯环上，而氮原子被连接到R2上。In another embodiment, the invention relates to compounds of formula I wherein s is 1 and U is CO-NR 11 . In this class of compounds, the carbonyl group of CO-NR 11 is attached to the benzene ring of formula I, while the nitrogen atom is attached to R 2 .

在另一个实施方案中，本发明涉及其中R11是氢原子的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 11 is a hydrogen atom.

在另一个实施方案中，本发明涉及其中X是CO的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein X is CO.

在另一个实施方案中，本发明涉及其中X是SO2的式I的化合物，前提是当X是SO2时，q时0。In another embodiment, the invention relates to compounds of formula I wherein X is SO2 , with the proviso that when X is SO2 , q is 0.

在另一个实施方案中，本发明涉及其中q是0的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein q is zero.

在另一个实施方案中，本发明涉及其中q是1的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein q is 1 .

在另一个实施方案中，本发明涉及其中q是1和Z是O的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein q is 1 and Z is O.

在另一个实施方案中，本发明涉及其中q是1和Z是S的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein q is 1 and Z is S.

在另一个实施方案中，本发明涉及其中X是CO，q是1和Z是O的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein X is CO, q is 1 and Z is O.

在另一个实施方案中，本发明涉及其中X是CO，q是1和Z是S的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein X is CO, q is 1 and Z is S.

在另一个实施方案中，本发明涉及其中X是CO和q是0的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein X is CO and q is 0.

在另一个实施方案中，本发明涉及其中X是SO2和q是0的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein X is SO2 and q is 0.

在另一个实施方案中，本发明涉及其中R1选自酰基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基和氰基-C3-8-环烷(链烯)基-C6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein R 1 is selected from acyl, hydroxy-C 1-6 -alk(en/alkyn)yl, hydroxy-C 3-8 -cycloalk(en)yl, hydroxy- C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl, halo-C 3- 8 -cycloalk(en)yl, halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, cyano-C 1-6 -alk( Alken/alkynyl, cyano-C 3-8 -cycloalk(en)yl and cyano-C 3-8 -cycloalk(alken)yl-C6-alk(en/alkyn)yl A compound of formula I.

本发明的一个实施方案涉及其中R1选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基和C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的通式I的化合物。One embodiment of the present invention relates to wherein R 1 is selected from the group consisting of hydrogen, C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl and C 3-8 -cycloalk(en)yl Compounds of the general formula I that are en)yl-C 1-6 -alk(alken/alkyn)yl.

本发明的一个优选实施方案涉及其中R1选自氢和C1-6-烷(链烯/炔)基的式I的化合物。A preferred embodiment of the invention relates to compounds of formula I, wherein R 1 is selected from hydrogen and C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及中R1是C1-6-烷(链烯/炔)基，典型地是C1-3-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein R 1 is C 1-6 -alk(en/yn)yl, typically C 1-3 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R1是氢原子的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 1 is a hydrogen atom.

在另一个实施方案中，本发明涉及其中R2选自氢、酰基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基、氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、NR10R10′-C1-6-烷(链烯/炔)基、NR10R10′-C3-8-环烷(链烯)基和NR10R10′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物；其中In another embodiment, the present invention relates to wherein R 2 is selected from hydrogen, acyl, hydroxy-C 1-6 -alk(en/alkyn)yl, hydroxy-C 3-8 -cycloalk(en)yl, Hydroxy-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, cyano-C 1-6 -alk(en/alkyn)yl, cyano-C 3-8 -Cycloalk(en)yl, cyano-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, NR 10 R 10′ -C 1 -6 -alk(en/alkyn)yl, NR 10 R 10′ -C 3-8 -cycloalk(en)yl and NR 10 R 10′ -C 3-8 -cycloalk(en)yl- Compounds of formula I of C 1-6 -alk(en/alkyn)yl; wherein

R10和R10′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基和氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基，或R 10 and R 10' are independently selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl Base-C 1-6 -alk(alkene/alkynyl)yl, Hydroxy-C 1-6 -alk(alkene/alkynyl)yl, Hydroxy-C 3-8 -Cycloalkane(enyl)yl, Hydroxy-C 3-8 -Cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl, halo-C 3-8 -cycloalk(en)yl, halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, cyano-C 1-6 -alk(alk) En/alkynyl) group, cyano-C 3-8 -cycloalk(en)yl and cyano-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyne) base, or

R10和R10′和其与之相连的氮原子一起形成一种任选地包含1、2或3个另外的杂原子的5-8员饱和或不饱和的环；R 10 and R 10' together with the nitrogen atom to which they are attached form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms;

前提是当s是1和R2是氢原子或酰基时，U是O或S。Provided that U is O or S when s is 1 and R2 is a hydrogen atom or an acyl group.

当R2表示NR10R10′-C1-6烷(链烯/炔)基、NR10R10′-C3-8-环烷(链烯)基或NR10R10′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基时，该氮原子通过C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基或C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基被连接到该分子的剩余部分上。When R 2 represents NR 10 R 10′ -C 1-6 alk(en/alkyn)yl, NR 10 R 10′ -C 3-8 -cycloalk(en)yl or NR 10 R 10′ -C 3 When -8 -cycloalk(alkene)yl-C 1-6 -alk(alkene/alkyne)yl, the nitrogen atom passes through C 1-6 -alk(en/alkyn)yl, C 3-8 -ring Alk(en)yl or C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl is attached to the remainder of the molecule.

在另一个实施方案中，本发明涉及其中R2选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤素、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基和氰基的式I的化合物；In another embodiment, the present invention relates to wherein R 2 is selected from hydrogen, C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cyclo Alk(en)yl-C 1-6 -alk(en/alkyn)yl, Ar, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3-8 -cycloalkane(alkyn) alken)yl, Ar-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, halogen, halo-C 1-6 -alk(en/alkyne) group, halo-C 3-8 -cycloalk(en)yl, halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl and cyano A compound of formula I;

前提是当R2是卤素或氰基时s是0；和provided that s is 0 when R is halo or cyano; and

前提是当s是1和R2是氢原子时U是O或S。The premise is that U is O or S when s is 1 and R2 is a hydrogen atom.

在另一个实施方案中，本发明涉及其中R2选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、Ar、Ar-C1-6-烷(链烯/炔)基、卤素、卤代-C1-6-烷(链烯/炔)基和氰基的式I的化合物；In another embodiment, the present invention relates to wherein R 2 is selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, Ar, Ar-C 1 Compounds of formula I of -6 -alk(en/alkyn)yl, halogen, halo-C 1-6 -alk(en/alkyn)yl and cyano;

前提是当R2是卤素或氰基时，s是0；和provided that when R2 is halo or cyano, s is 0; and

前提是当s是1和R2是氢原子时U是O或S。The premise is that U is O or S when s is 1 and R2 is a hydrogen atom.

在一个优选的实施方案中，本发明涉及其中R2选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、Ar-C1-6-烷(链烯/炔)基、卤素和氰基的式I的化合物；In a preferred embodiment, the present invention relates to wherein R 2 is selected from C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, Ar-C 1-6 - Alk(en/alkyn)yl, halogen and cyano compounds of formula I;

前提是当R2是卤素或氰基是，s是0。Provided that s is 0 when R2 is halogen or cyano.

在另一个实施方案中，本发明涉及其中R2是氢原子的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R2 is a hydrogen atom.

在另一个实施方案中，本发明涉及其中R2不是氢原子的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R2 is other than a hydrogen atom.

在另一个实施方案中，本发明涉及其中R2是C1-6-烷(链烯/炔)基、C1-3-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 2 is C 1-6 -alk(en/yn)yl, C 1-3 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R2是C3-8-环烷(链烯)基，典型地是C3-6-环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 2 is C 3-8 -cycloalk(en)yl, typically C 3-6 -cycloalk(en)yl.

在另一个实施方案中，本发明涉及其中R2是Ar的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R2 is Ar.

在另一个实施方案中，本发明涉及其中R2不是Ar的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R2 is other than Ar.

在另一个实施方案中，本发明涉及其中R2是Ar-C1-6-烷(链烯/炔)基，典型地是Ar-C1-3-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to the formula wherein R 2 is Ar-C 1-6 -alk(en/yn)yl, typically Ar-C 1-3 -alk(en/yn)yl Compounds of I.

在另一个实施方案中，本发明涉及其中R2是卤素原子，典型地是氯原子、溴原子或碘原子的的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein R2 is a halogen atom, typically a chlorine atom, bromine atom or iodine atom.

在另一个实施方案中，本发明涉及其中R2是卤代-C1-6-烷(链烯/炔)基，典型地是卤代-C1-3-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to wherein R 2 is halo-C 1-6 -alk(en/yn)yl, typically halo-C 1-3 -alk(en/yn)yl A compound of formula I.

在另一个实施方案中，本发明涉及式I的化合物，其中R2不是卤代-C1-6-烷(链烯/炔)基，典型地不是卤代-C1-3-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 2 is not halo-C 1-6 -alk(en/alkyn)yl, typically not halo-C 1-3 -alk(alk(alkene) En/alkynyl) compound of formula I.

在另一个实施方案中，本发明涉及其中R2是氰基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R2 is cyano.

在另一个实施方案中，本发明涉及其中R10和R10′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein R 10 and R 10′ are independently selected from hydrogen, C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl, Compounds of formula I that are C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R10和R10′独立地选自氢和C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 10 and R 10' are independently selected from hydrogen and C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中s是1，U是O和R2选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基和卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to wherein s is 1, U is O and R is selected from the group consisting of C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3-8 - Cycloalk(en)yl, Ar-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn) Alkynyl, halo-C 3-8 -cycloalk(en)yl and halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl A compound of formula I.

在另一个实施方案中，本发明涉及其中s是1，U是O和R2选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、Ar-C1-6-烷(链烯/炔)基和卤代-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to wherein s is 1, U is O and R is selected from the group consisting of C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl, Ar-C 1-6 -alk(en/yn)yl and halo-C 1-6 -alk(en/yn)yl compounds of formula I.

在另一个实施方案中，本发明涉及其中s是1，U是O和R2选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基和Ar-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein s is 1, U is O and R 2 is selected from the group consisting of C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl and Compounds of formula I that are Ar-C 1-6 -alk(en/alkyn)yl.

在另一个实施方案中，本发明涉及其中s是1，U是S和R2选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基和Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to wherein s is 1, U is S and R 2 is selected from the group consisting of C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3-8 - Cycloalk(en)yl and Ar-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl compounds of formula I.

在另一个实施方案中，本发明涉及其中s是1，U是S和R2选自C1-6-烷(链烯/炔)基和Ar-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to the group wherein s is 1, U is S and R 2 is selected from the group consisting of C 1-6 -alk(en/alkyn)yl and Ar-C 1-6 -alk(en/alkyne) )-based compound of formula I.

在另一个实施方案中，本发明涉及其中s是1，U是S和R2选自C3-8-环烷(链烯)基和Ar-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein s is 1, U is S and R is selected from C 3-8 -cycloalk(en)yl and Ar-C 1-6 -alk(alkene/yne) The compound of formula I of group.

在另一个实施方案中，本发明涉及其中s是0和R2选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar，卤素、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基和氰基的式I的化合物。In another embodiment, the present invention relates to wherein s is 0 and R 2 is selected from C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -Cycloalk(en)yl-C 1-6 -alk(en/yn)yl, Ar, halogen, halo-C 1-6 -alk(en/yn)yl, halo-C 3- 8 -Cycloalk(en)yl, halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl and cyano compounds of formula I.

在另一个实施方案中，本发明涉及其中s是0和R2选自C1-6-烷(链烯/炔)基、Ar，卤素、卤代-C1-6-烷(链烯/炔)基和氰基的式I的化合物。In another embodiment, the present invention relates to wherein s is 0 and R 2 is selected from the group consisting of C 1-6 -alk(en/yn)yl, Ar, halogen, halo-C 1-6 -alk(en/yn) Alkynyl) and cyano compounds of formula I.

在另一个实施方案中，本发明涉及其中s是0和R2选自C1-6-烷(链烯/炔)基、卤素和氰基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein s is 0 and R2 is selected from Ci -6 -alk(en/yn)yl, halogen and cyano.

在另一个实施方案中，本发明涉及其中s是1，U是CO-O和R2选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein s is 1, U is CO-O and R 2 is selected from the group consisting of C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(alkene) A compound of formula I which is C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中s是1，U是CO-O和R2是C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein s is 1, U is CO—O and R 2 is C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中s是1，U是CO-NR11，R11是氢原子和R2不是C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基、氰基-C3-8-环烷(链烯)基和Ar的式I的化合物。In another embodiment, the invention relates to wherein s is 1, U is CO-NR 11 , R 11 is a hydrogen atom and R 2 is other than C 3-8 -cycloalk(en)yl, hydroxy-C 3-8 Compounds of formula I of -cycloalk(en)yl, halo-C 3-8 -cycloalk(en)yl, cyano-C 3-8 -cycloalk(en)yl and Ar.

在另一个实施方案中，本发明涉及其中s是1，U是CO-NR11和R2选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein s is 1, U is CO-NR 11 and R 2 is selected from the group consisting of C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(alkene) ) group, C 3-8 -cycloalkan(en)yl-C 1-6 -alk(alkene/alkyn)yl compound of formula I.

在另一个实施方案中，本发明涉及其中s是1，U是CO-NR11和R2是C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein s is 1, U is CO-NR 11 and R 2 is C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R11是氢原子。In another embodiment, the invention relates to wherein R 11 is a hydrogen atom.

在另一个实施方案中，本发明涉及其中R3选自杂环烷(链烯)基、C1-6-烷(链烯/炔)基杂环烷(链烯)基、Ar-杂环烷(链烯)基、Ar-C1-6-烷(链烯/炔)基杂环烷(链烯)基、C1-6-烷(链烯/炔)氧基-杂环烷(链烯)基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-杂环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、羟基-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、羟基-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、卤代-杂环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基、氰基-杂环烷(链烯)基、氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、氰基-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、酰基C1-6-烷(链烯/炔)基、酰基-C3-8-环烷(链烯)基、酰基-杂环烷(链烯)基、酰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、酰基-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、酰基-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、NR12R12′的式I的化合物；其中In another embodiment, the present invention relates to wherein R 3 is selected from the group consisting of heterocycloalk(en)yl, C 1-6 -alk(en/alkyn)yl heterocycloalk(en)yl, Ar-heterocycle Alk(en)yl, Ar-C 1-6 -alk(en/yn)ylheterocycloalk(alken)yl, C 1-6 -alk(en/alkyne)oxy-heterocycloalkane( Alken) group, Hydroxy-C 1-6 -alk(alkene/alkyne) group, Hydroxy-C 3-8 -Cycloalkane(alkene) group, Hydroxy-heterocycloalkane(alkene) group, Hydroxy-C 3-8 -Cycloalkane (alkene) group-C 1-6 -alk(alkene/alkyne) group, hydroxyl-C 1-6 -alk(alkene/alkynyl) group-C 3-8 -cycloalkane( Alken) group, hydroxy-C 1-6 -alk(alkene/alkyne) group-heterocycloalkane(alkene) group, halo-heterocycloalkane(alkene) group, halo-C 1-6- Alk(en/alkyn)yl-heterocycloalkalk(en)yl, cyano-C 1-6 -alk(en/alkyn)yl, cyano-C 3-8 -cycloalk(en)yl , cyano-heterocycloalkane(alkene)yl, cyano-C 3-8 -cycloalkane(alkene)yl-C 1-6 -alk(alkene/alkyne)yl, cyano-C 1-6 -Alk(en/alkyn)yl-C 3-8 -cycloalk(en)yl, cyano-C 1-6 -alk(en/alkyn)yl-heterocycloalk(en)yl, acyl C 1-6 -alk(en/alkyn)yl, acyl-C 3-8 -cycloalk(en)yl, acyl-heterocycloalk(en)yl, acyl-C 3-8 -cycloalkane( Alken)yl-C 1-6 -alk(en/alkyn)yl, acyl-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(en)yl, acyl- Compounds of formula I of C 1-6 -alk(en/alkyn)yl-heterocycloalkane(alken)yl, NR 12 R 12′ ; wherein

R12和R12′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-杂环烷(链烯)基、Ar-氧基-C1-6-烷(链烯/炔)基、Ar-氧基-C3-8-环烷(链烯)基、Ar-氧基C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-氧基-杂环烷(链烯)基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基和氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基，或R 12 and R 12′ are independently selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl Base-C 1-6 -alk(en/alkyn)yl, Ar, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3-8 -cycloalk(en)yl, Ar -C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Ar-heterocycloalk(en)yl, Ar-oxy-C 1-6 -alk (alkene/alkynyl) group, Ar-oxyl-C 3-8 -cycloalk(en)yl, Ar-oxyl C 3-8 -cycloalk(en)yl-C 1-6 -alk( Alken/Alkyn)yl, Ar-Oxy-Heterocycloalkane(alkene)yl, Hydroxy-C 1-6 -Alk(alkene/Alkyn)yl, Hydroxy-C 3-8 -Cycloalkane(alkene)yl Hydroxy-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl, halo -C 3-8 -cycloalk(en)yl, halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, cyano-C 1- 6 -alk(en/alkyn)yl, cyano-C 3-8 -cycloalk(en)yl and cyano-C 3-8 -cycloalk(en)yl-C 1-6 -alk( alkenyl/alkynyl) group, or

R12和R12′和其与之相连的氮原子一起形成一种任选地包含1、2或3个另外的杂原子的5-8员饱和或不饱和的环；R 12 and R 12' together with the nitrogen atom to which they are attached form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms;

前提是当R3是NR12R12′时，q是0。Provided that q is 0 when R 3 is NR 12 R 12′ .

当R3表示NR12R12′-C1-6-烷(链烯/炔)基、NR12R12′-C3-8-环烷(链烯)基或NR12R12′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基时，氮原子通过C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基或C3-8-环烷(链烯)基-C6-烷(链烯/炔)基被连接到该X-(Z)p基上。When R 3 represents NR 12 R 12 ′-C 1-6 -alk(en/alkyn)yl, NR 12 R 12′ -C 3-8 -cycloalk(en)yl or NR 12 R 12′ -C When 3-8 -cycloalk(alkene)yl-C 1-6 -alk(en/alkyn)yl, the nitrogen atom passes through C 1-6 -alk(en/alkyn)yl, C 3-8 -ring An alk(en)yl or C 3-8 -cycloalk(en)yl-C6-alk(alken/alkyn)yl group is attached to the X-(Z)p group.

在另一个实施方案中，本发明涉及其中R3选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、杂环烷(链烯)基-C16-烷(链烯/炔)基、杂环烷(链烯)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)氧基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-C3-8-环烷(链烯)基、Ar-氧基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)氧基-羰基-C1-6-烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基-Ar、卤代-C3-8-环烷(链烯)基-Ar、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基-Ar、卤代-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基-Ar、NR12R12′、任选地被取代的NR12R12′-C1-6-烷(链烯/炔)基、任选地被取代的NR12R12′-C3-8-环烷(链烯)基和任选地被取代的HR12R12′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein R 3 is selected from C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalkane( Alken) base-C 1-6 -alk(alkene/alkyn)yl, C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(en)yl, heterocycloalkane( Alken) base-C16-alk(alkene/alkyne)yl, heterocycloalkane(alkene)yl, Ar, Ar-C 1-6 -alk(alkene/alkynyl)yl, Ar-C 3-8- Cycloalk(en)yl, Ar-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Ar-C 1-6 -alk(en/alkyne) ) group-C 3-8 -cycloalk(alkene)yl, C 1-6 -alk(alkene/alkyne)oxy-C 1-6 -alk(alkene/alkynyl)yl, C 3-8- Cycloalk(alkene)oxy-C 1-6 -alk(en/alkyn)yl, C 1-6 -alk(en/alkyn)oxy-C 3-8 -cycloalk(en)yl , Ar-oxyl-C 1-6 -alk(alkene/alkynyl)yl, Ar-C 1-6 -alk(alkene/alkynyl)oxy-C 1-6 -alk(en/alkynyl)yl , C 1-6 -alk(alkene/alkynyl)oxy-carbonyl-C 1-6 -alk(en/alkynyl)yl, C 3-8 -cycloalkane(alkenyl)oxy-carbonyl-C 1 -6 -alk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(alkene/alkyne)oxy-carbonyl-C 1-6 -alk(alkene/ Alkynyl) group, halo-C 1-6 -alk(alkene/alkyn)yl, halo-C 3-8 -cycloalk(en)yl, halo-C 3-8 -cycloalk(alkene) ) base-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(en)yl, halo- C 1-6 -alk(en/alkyn)yl-Ar, halo-C 3-8 -cycloalk(en)yl-Ar, halo-C 3-8 -cycloalk(en)yl- C 1-6 -alk(en/alkyn)yl-Ar, halo-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(en)yl-Ar, NR 12 R 12' , optionally substituted NR 12 R 12' -C 1-6 -alk(alkene/alkyn)yl, optionally substituted NR 12 R 12' -C 3-8 -cycloalkane ( Compounds of formula I of alken)yl and optionally substituted HR 12 R 12′ -C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在另-个实施方案中，本发明涉及其中R3选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、杂环烷(链烯)基-C1-6-烷(链烯/炔)基、杂环烷(链烯)基、Ar、Ar-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、Ar-氧基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基-Ar、NR12R12′、任选地被取代的NR12R12′-C1-6-烷(链烯/炔)基、和任选地被取代的NR12R12′-C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the present invention relates to wherein R 3 is selected from C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalkane (Alken)yl-C 1-6 -alk(en/alkyn)yl, Heterocycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Heterocycloalk(en)yl Base, Ar, Ar-C 1-6 -alk(alkene/alkynyl)yl, C 1-6 -alk(alkene/alkynyl)oxy-C 1-6 -alk(alkene/alkynyl)yl, Ar -Oxy-C 1-6 -alk(alkene/alkyne)yl, Ar-C1-6-alk(alkene/alkynyl)oxy-C 1-6 -alk(alkene/alkynyl)yl, C 1 -6 -alk(alkene/alkyne)oxy-carbonyl-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/yn)yl-Ar, NR 12 R 12′ , optionally substituted NR 12 R 12′ -C 1-6 -alk(en/yn)yl, and optionally Compounds of formula I that are NR 12 R 12′ -C 3-8 -cycloalk(en)yl substituted.

在一个优选的实施方案中，本发明涉及其中R3是C1-6-烷(链烯/炔)基，典型地是C1-3-烷(链烯/炔)基的式I的化合物。In a preferred embodiment, the invention relates to compounds of formula I wherein R is C 1-6 -alk(en/alkyn) yl , typically C 1-3 -alk(en/alkyn)yl .

在另一个实施方案中，本发明涉及其中R3是C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is C 3-8 -cycloalk(en)yl.

在另一个实施方案中，本发明涉及其中R3是C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R3是Ar的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R3 is Ar.

在另一个实施方案中，本发明涉及其中R3是杂环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R3 is heterocycloalk(en)yl.

在另一个实施方案中，本发明涉及其中R3不是杂环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R3 is other than heterocycloalk(en)yl.

在另一个实施方案中，本发明涉及其中R3是杂环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is heterocycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R3不是杂环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is other than heterocycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R3是Ar-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is Ar-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R3是C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is C 1-6 -alk(en/yn)oxy-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R3不是C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is other than C 1-6 -alk(alken/yn)oxy-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R3是Ar-氧基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is Ar-oxy-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R3是Ar-C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is Ar-C 1-6 -alk(alken/alkyn)oxy-C 1-6 -alk(alken/alkyn)yl.

在另一个实施方案中，本发明涉及其中R3是C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is C 1-6 -alk(alken/yn)oxy-carbonyl-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R3是卤代-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is halo-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R3是卤代-C1-6-烷(链烯/炔)基-Ar的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is halo-C 1-6 -alk(en/yn)yl-Ar.

在另一个实施方案中，本发明涉及其中R3不是卤代-C1-6-烷(链烯/炔)基-Ar的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is other than halo-C 1-6 -alk(en/yn)yl-Ar.

在另一个实施方案中，本发明涉及其中R3是NR12R12′的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R3 is NR12R12 ' .

在另一个实施方案中，本发明涉及其中R3不是NR12R12′的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R3 is other than NR12R12 ' .

在另一个实施方案中，本发明涉及其中R3是任选地被取代的NR12R12′-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is optionally substituted NR 12 R 12′ -C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R3不同于任选地被取代的NR12R12′-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is different from optionally substituted NR 12 R 12′ -C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R3是任选地被取代的NR12R12′-C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is optionally substituted NR 12 R 12′ -C 3-8 -cycloalk(en)yl.

在另一个实施方案中，本发明涉及其中R3不同于任选地被取代的NR12R12′-C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 3 is different from optionally substituted NR 12 R 12′ -C 3-8 -cycloalk(en)yl.

在另一个实施方案中，本发明涉及其中R3是任选地被取代的NR12R12′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to wherein R 3 is optionally substituted NR 12 R 12′ -C 3-8 -cycloalk(en)yl-C 1-6 -alk(alken/alkyne )-based compound of formula I.

在另一个实施方案中，本发明涉及其中R3不同于任选地被取代的NR12R12′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to wherein R 3 is different from optionally substituted NR 12 R 12′ -C 3-8 -cycloalk(en)yl-C 1-6 -alk(alken/ A compound of formula I that is an alkynyl group.

在另一个实施方案中，本发明涉及其中R12和R12′独立地选自Ar-杂环烷(链烯)基、Ar-氧基-C1-6-烷(链烯/炔)基、Ar-氧基-C3-8-环烷(链烯)基、Ar-氧基C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-氧基-杂环烷(链烯)基、羟基-C1-6烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基和氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基，或In another embodiment, the present invention relates to wherein R 12 and R 12′ are independently selected from Ar-heterocycloalk(en)yl, Ar-oxy-C 1-6 -alk(en/yn)yl , Ar-oxyl-C 3-8 -cycloalk(en)yl, Ar-oxyl-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl, Ar-oxyl-heterocycloalkane (alkene) group, hydroxy-C 1-6 alk(alkene/alkyne) group, hydroxy-C 3-8 -cycloalkane (alkene) group, hydroxy-C 3-8 -Cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl, halo-C 3-8 -cycloalkane (Alken)yl, Halo-C 3-8 -Cycloalkane(alkene)yl-C 1-6 -Alk(alkene/Alkyne)yl, Cyano-C 1-6 -Alk(alkene/Alkyne) ) group, cyano-C 3-8 -cycloalk(en)yl and cyano-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl, or

R12和R12′和其与之相连的氮原子一起形成一种任选地包含1、2或3个另外的杂原子的5-8员饱和或不饱和的环；R 12 and R 12' together with the nitrogen atom to which they are attached form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms;

的式I的化合物。A compound of formula I.

在另一个实施方案中，本发明涉及其中R12和R12′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein R 12 and R 12′ are independently selected from hydrogen, C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Ar, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3- 8 -Cycloalk(en)yl, Ar-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl compounds of formula I.

在另一个实施方案中，本发明涉及其中R12和R12′独立地选自氢、C1-6-烷(链烯/炔)基和Ar的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 12 and R 12' are independently selected from hydrogen, C 1-6 -alk(en/yn)yl and Ar.

在另一个实施方案中，本发明涉及其中R12和R12′中至少一个是氢原子的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein at least one of R12 and R12 ' is a hydrogen atom.

在另一个实施方案中，本发明涉及其中R12和R12′中至少一个是C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein at least one of R 12 and R 12' is C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R12和R12′中至少一个是Ar的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein at least one of R12 and R12 ' is Ar.

在另一个实施方案中，本发明涉及其中X是CO，q是1，Z是O和R3选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、ArC3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)基-C3-s-环烷(链烯)基、C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)氧基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-C3-8-环烷(链烯)基、Ar-氧基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基和卤代-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the present invention relates to wherein X is CO, q is 1, Z is O and R 3 is selected from the group consisting of C 1-6 -alk(en/yn)yl, C 3-8 -cycloalkane(chain) alken) group, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, C 1-6 -alk(en/alkyn)yl-C 3-8- Cycloalk(alkene)yl, Ar, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3-8 -cycloalk(en)yl, ArC 3-8 -cycloalk(en)yl En)yl-C 1-6 -alk(en/alkyn)yl, Ar-C 1-6 -alk(en/alkyn)yl-C3-s-cycloalk(en)yl, C 1-6 -Alk(alkene/alkyne)oxy-C 1-6 -alk(en/alkyne)yl, C 3-8 -cycloalk(alkene)oxy-C 1-6 -alk(alkene/alkyne) ) group, C 1-6 -alk(alkene/alkyne)oxy-C 3-8 -cycloalkane(en)yl, Ar-oxyl-C 1-6 -alk(alkene/alkynyl)yl, Ar-C 1-6 -alk(alkene/alkynyl)oxy-C 1-6 -alk(en/alkynyl)yl, halo-C 1-6 -alk(en/alkynyl)yl, halo -C 3-8 -cycloalk(en)yl, halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl and halo-C 1- 6 -Alk(en/yn)yl-C 3-8 -cycloalk(en)yl compounds of formula I.

在另一个实施方案中，本发明涉及其中X是CO，q是1，Z是O和R3选自C1-6-烷(链烯/炔)基、Ar、Ar-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基和卤代-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein X is CO, q is 1, Z is O and R 3 is selected from C 1-6 -alk(en/yn)yl, Ar, Ar-C 1-6 - Alk(alkene/alkyne)yl, C 1-6 -alk(alkene/alkynyl)oxy-C 1-6 -alk(alkene/alkynyl)yl, Ar-C 1-6 -alk(alkene/alkynyl) Alkynyl)oxy-C 1-6 -alk(alken/yn)yl and halo-C 1-6 -alk(alken/yn)yl compounds of formula I.

在另一个实施方案中，本发明涉及其中X是CO，q是1，Z是O和R3不是C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein X is CO, q is 1, Z is O and R 3 is other than C 1-6 -alk(alkene/alkyne)oxy-C 1-6 -alk(alkene) /Alkynyl) compound of formula I.

在另一个实施方案中，本发明涉及其中X是CO，q是1，Z是O和R3是C1-6-烷(链烯/炔)基，典型地是C1-3-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to wherein X is CO, q is 1, Z is O and R 3 is C 1-6 -alk(en/yn)yl, typically C 1-3 -alk( A compound of formula I that is an alkenyl/alkynyl).

在另一个实施方案中，本发明涉及其中X是CO，q是1，Z是S和R3选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基和Ar-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the present invention relates to wherein X is CO, q is 1, Z is S and R 3 is selected from the group consisting of C 1-6 -alk(en/yn)yl, C 3-8 -cycloalkane(chain) alken) group, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, C 1-6 -alk(en/alkyn)yl-C 3-8- Cycloalk(en)yl, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3-8 -cycloalk(en)yl, Ar-C 3-8 -cycloalk(en)yl Alken)-C 1-6 -alk(en/alkyn)yl and Ar-C 1-6 -alk(en/alkyn)-C 3-8 -cycloalk(alkene)yl of formula I compound.

在另一个实施方案中，本发明涉及其中X是CO，q是1，Z是S和R3选自C1-6-烷(链烯/炔)基和Ar-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein X is CO, q is 1, Z is S and R 3 is selected from C 1-6 -alk(en/yn)yl and Ar-C 1-6 -alk( A compound of formula I that is an alkenyl/alkynyl).

在另一个实施方案中，本发明涉及其中X是CO，q是1，Z是S和R3是C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein X is CO, q is 1, Z is S and R 3 is C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中X是CO，q是0，R3选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、杂环烷(链烯)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、Ar-氧基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)氧基-羰基-C1-6-烷(链烯/炔)基，C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基-Ar、卤代-C3-8-环烷(链烯)基-Ar、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基-Ar、卤代-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基-Ar、NR12R12′、任选地被取代的NR12R12′-C1-6-烷(链烯/炔)基、和任选地被取代的NR12R12′-C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the present invention relates to wherein X is CO, q is 0, R 3 is selected from C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(en)yl Alken)yl, Heterocycloalkane(alkene)yl, Ar, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3-8 -cycloalk(en)yl, Ar-C 3 -8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Ar-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(alkyn)yl alken) group, Ar-oxyl-C 1-6 -alk(alkene/alkynyl)yl, Ar-C 1-6 -alk(alkene/alkynyl)oxy-C 1-6 -alk(alkene/alkynyl) Alkynyl, C 1-6 -alk(alkene/alkynyl)oxy-carbonyl-C 1-6 -alk(en/alkynyl)yl, C 3-8 -cycloalkane(alkenyl)oxy-carbonyl -C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)oxy-carbonyl-C 1-6 - Alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl, halo-C 3-8 -cycloalk(en)yl, halo-C 3-8- Cycloalk(alkene)yl-C 1-6 -alk(en/alkyn)yl, Halo-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(alkene) group, halo-C 1-6 -alk(en/alkyn)yl-Ar, halo-C 3-8 -cycloalk(en)yl-Ar, halo-C 3-8 -cycloalkane( Alken)yl-C 1-6 -alk(en/alkyn)yl-Ar, halo-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(en)yl -Ar, NR 12 R 12' , optionally substituted NR 12 R 12' -C 1-6 -alk(en/alkyn)yl, and optionally substituted NR 12 R 12' -C 3 Compounds of formula I that are -8 -cycloalk(en)yl.

在另一个实施方案中，本发明涉及其中X是CO，q是0，R3选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、杂环烷(链烯)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-氧基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基-Ar、NR12R12′、任选地被取代的NR12R12′-C1-6-烷(链烯/炔)基、和任选地被取代的NR12R12′-C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the present invention relates to wherein X is CO, q is 0, R 3 is selected from C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, heterocycloalk(en)yl, Ar, Ar-C 1-6 -alk(en/alkyn) Alkynyl) group, Ar-oxyl-C 1-6 -alk(alkene/alkynyl)yl, C 1-6 -alk(alkene/alkynyl)oxy-carbonyl-C 1-6 -alk(alkene/alkynyl) Alkynyl) group, halo-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl-Ar, NR 12 R 12′ , optionally Formulas I _ _ _ _ compound of.

在另一个实施方案中，本发明涉及其中X是SO2，q是0和R3选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the present invention relates to wherein X is SO 2 , q is 0 and R 3 is selected from C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl , C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalkane( Alken)yl, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3-8 -cycloalk(en)yl, Ar-C 3-8 -cycloalk(en)yl Compounds of formula I of -C 1-6 -alk(en/yn)yl, Ar-C 1-6 -alk(en/yn)yl-C 3-8 -cycloalk(en/yn)yl.

在另一个实施方案中，本发明涉及其中X是SO2，q是0和R3选自C1-6-烷(链烯/炔)基和Ar-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein X is SO 2 , q is 0 and R 3 is selected from the group consisting of C 1-6 -alk(en/yn)yl and Ar-C 1-6 -alk(en/alkyn) A compound of formula I that is an alkynyl group.

在一个优选的实施方案中，本发明涉及其中R3是Ar和q是1的式I的化合物。In a preferred embodiment, the invention relates to compounds of formula I, wherein R 3 is Ar and q is 1 .

在一个优选的实施方案中，本发明涉及其中R3是Ar和q是0的式I的化合物。In a preferred embodiment, the invention relates to compounds of formula I, wherein R3 is Ar and q is zero.

在一个优选的实施方案中，本发明涉及其中当q是0时R3不是Ar的式I的化合物。In a preferred embodiment, the invention relates to compounds of formula I, wherein R 3 is other than Ar when q is 0.

在另一个实施方案中，本发明涉及其中Y是式XXIV、XXV、XXVII、XXXXI或XXXXII的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein Y is formula XXIV, XXV, XXVII, XXXXI or XXXXII.

在另一个实施方案中，本发明涉及其中Y是式XXIV的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein Y is formula XXIV.

在另一个实施方案中，本发明涉及其中Y是式XXV的式I的化合物。In another embodiment, the present invention is concerned with compounds of formula I wherein Y is formula XXV.

在另一个实施方案中，本发明涉及其中Y是式XXVII的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein Y is formula XXVII.

在另一个实施方案中，本发明涉及其中Y是式XXXXI的式I的化合物。In another embodiment, the present invention is concerned with compounds of formula I wherein Y is formula XXXXI.

在另一个实施方案中，本发明涉及其中Y是式XXXXII的式I的化合物。In another embodiment, the present invention is concerned with compounds of formula I wherein Y is formula XXXXII.

在另一个实施方案中，本发明涉及其中W是氧原子的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein W is an oxygen atom.

在另一个实施方案中，本发明涉及其中W是硫原子的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein W is a sulfur atom.

在另一个实施方案中，本发明涉及其中V是氮原子的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein V is a nitrogen atom.

在另一个实施方案中，本发明涉及其中V是CH的式I的化合物。In another embodiment, the present invention is concerned with compounds of formula I, wherein V is CH.

在另一个实施方案中，本发明涉及其中T是氮原子的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein T is a nitrogen atom.

在另一个实施方案中，本发明涉及其中T是氧原子的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein T is an oxygen atom.

在另一个实施方案中，本发明涉及其中各R5独立地选自Ar-氧基-C1-6-烷(链烯/炔)基、Ar-氧基-C3-8-环烷(链烯)基、Ar-氧基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、酰基、-CO-NR6R6′、氰基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基和氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein each R 5 is independently selected from Ar-oxy-C 1-6 -alk(en/alkyn)yl, Ar-oxy-C 3-8 -cycloalkane ( Alken)yl, Ar-oxyl-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, acyl, -CO-NR 6 R 6′ , cyano , cyano-C 1-6 -alk(en/alkyn)yl, cyano-C 3-8 -cycloalk(en)yl and cyano-C 3-8 -cycloalk(en)yl- C 1-6 -Alk(en/yn)yl compounds of formula I.

在另一个实施方案中，本发明涉及其中各R5独立地选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)基杂环烷(链烯)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基、C3-8-环烷(链烯)氧基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)氧基、Ar-氧基、C1-6-烷(链烯/炔)氧基-羰基、卤素、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、NR7R7′、S-R8和SO2R8，或两个毗邻的R5与该芳族基团一起形成一种任选地包含一个或两个杂原子的5-8员环的式I的化合物。In another embodiment, the present invention relates to wherein each R 5 is independently selected from C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 - Cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, C 1-6 -alk(en/alkyn)yl heterocycloalk(en)yl, Ar, Ar-C 1 -6 -alk(en/alkyn)yl, Ar-C 3-8 -cycloalk(en)yl, Ar-C 3-8 -cycloalk(en)yl-C 1-6 -alk(alken)yl En/Alkyn)yl, C 1-6 -Alk(alkene/Alkyn)oxy, C 3-8 -Cycloalk(en)oxy, C 3-8 -Cycloalk(en)yl-C 1 -6 -alk(alkene/alkyne)oxy, Ar-oxyl, C 1-6 -alk(alkene/alkynyl)oxy-carbonyl, halogen, halo-C 1-6 -alk(alkene/alkynyl) Alkynyl) group, halo-C 3-8 -cycloalk(en)yl, halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, NR 7 R 7' , SR 8 and SO 2 R 8 , or two adjacent R 5 together with the aromatic group form a 5-8 membered ring of formula I optionally containing one or two heteroatoms compound of.

当R5表示NR7R7′-C1-6-烷(链烯/炔)基、NR7R7′-C3-8-环烷(链烯)基或NR7R7′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基时，该氮原子通过C1- 6-烷(链烯/炔)基、C3-8-环烷(链烯)基或C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基被连接到该分子的剩余部分上。When R 5 represents NR 7 R 7′ -C 1-6 -alk(en/alkyn)yl, NR 7 R 7′ -C 3-8 -cycloalk(en)yl or NR 7 R 7′ -C When 3-8 -cycloalkane (alkene) base-C 1-6 -alk(alkene/alkyne) group, the nitrogen atom passes through C 1- 6 -alk(alkene/alkynyl) group, C 3-8- Cycloalk(en)yl or C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl is attached to the remainder of the molecule.

在另一个实施方案中，本发明涉及其中各R5独立地选自C1-6-烷(链烯/炔)基、Ar、C1-6-烷(链烯/炔)氧基、卤素、-NR7R7′、-S-R8和-SO2R8，或两个毗邻的R5与该芳族基团一起形成一种任选地包含一个或两个杂原子的5-8员环的式I的化合物。In another embodiment, the present invention relates to wherein each R 5 is independently selected from C 1-6 -alk(en/yn)yl, Ar, C 1-6 -alk(en/yn)oxy, halogen , -NR 7 R 7′ , -SR 8 and -SO 2 R 8 , or two adjacent R 5 together with the aromatic group form a 5-8 membered optionally containing one or two heteroatoms A compound of formula I of the ring.

在一个优选的实施方案中，本发明涉及其中各R5独立地选自C1-6-烷(链烯/炔)基、Ar、C1-6-烷(链烯/炔)氧基、Ar-氧基、C1-6-烷(链烯/炔)基-杂环烷(链烯)基、C1-6-烷(链烯/炔)氧基-羰基、卤素、卤代-C1-6-烷(链烯/炔)基、NR7R7′、S-R8和SO2R8，或两个毗邻的R5与该芳族基团一起形成一种任选地包含一个或两个杂原子的5-8员环的式I的化合物。In a preferred embodiment, the present invention relates to wherein each R 5 is independently selected from C 1-6 -alk(en/yn)yl, Ar, C 1-6 -alk(en/yn)oxy, Ar-oxyl, C 1-6 -alk(en/alkyne)yl-heterocycloalkane(en)yl, C 1-6 -alk(en/alkyne)oxy-carbonyl, halogen, halo- C 1-6 -alk(en/alkyn)yl, NR 7 R 7′ , SR 8 and SO 2 R 8 , or two adjacent R 5 together with the aromatic group form a or a compound of formula I with a 5-8 membered ring of two heteroatoms.

在另一个实施方案中，本发明涉及其中一个R5是C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中一个R5是C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is C 3-8 -cycloalk(en)yl.

在另一个实施方案中，本发明涉及其中一个R5是C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中一个R5是Ar的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R5 is Ar.

在另一个实施方案中，本发明涉及其中一个R5是Ar-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is Ar-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中没有R5是Ar-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein none of R 5 is Ar-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中一个R5是Ar-C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is Ar—C 3-8 -cycloalk(en)yl.

在另一个实施方案中，本发明涉及其中没有R5是Ar-C3-s-环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein none of R 5 is Ar-C3-s-cycloalk(en)yl.

在另一个实施方案中，本发明涉及其中一个R5是Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is Ar-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中没有R5是Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein none of R 5 is Ar-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中一个R5是C1-6-烷(链烯/炔)氧基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is C 1-6 -alk(alkene/alkyn)oxy.

在另一个实施方案中，本发明涉及其中一个R5是C3-8-环烷(链烯)氧基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is C 3-8 -cycloalk(en)oxy.

在另一个实施方案中，本发明涉及其中一个R5是C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)氧基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is C 3-8 -cycloalk(en)yl-C 1-6 -alk(alken/alkyn)oxy.

在另一个实施方案中，本发明涉及其中一个R5是Ar-氧基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is Ar-oxy.

在另一个实施方案中，本发明涉及其中没有R5是Ar-氧基的式I的化合物。In another embodiment, the invention is concerned with compounds of formula I wherein none of R 5 is Ar-oxy.

在另一个实施方案中，本发明涉及其中一个R5是C1-6-烷(链烯/炔)基-杂环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is C 1-6 -alk(en/yn)yl-heterocycloalk(en)yl.

在另一个实施方案中，本发明涉及其中没有R5是C1-6-烷(链烯/炔)基-杂环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein none of R 5 is C 1-6 -alk(en/yn)yl-heterocycloalk(en)yl.

在另一个实施方案中，本发明涉及其中一个R5是C1-6-烷(链烯/炔)基-羰基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is C 1-6 -alk(en/yn)yl-carbonyl.

在另一个实施方案中，本发明涉及其中没有R5是C1-6-烷(链烯/炔)氧基-羰基。In another embodiment, the invention relates to wherein no R 5 is C 1-6 -alk(alkene/alkynyl)oxy-carbonyl.

在另一个实施方案中，本发明涉及其中一个R5是卤素原子的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is a halogen atom.

在另一个实施方案中，本发明涉及其中一个R5是卤代-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is halo-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中没有R5是卤代-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein none of R 5 is halo-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中一个R5是卤代-C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is halo-C 3-8 -cycloalk(en)yl.

在另一个实施方案中，本发明涉及其中没有R5是卤代-C3-8-环烷(链烯)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein none of R 5 is halo-C 3-8 -cycloalk(en)yl.

在另一个实施方案中，本发明涉及其中一个R5是卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中没有R5是卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein none of R 5 is halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中一个R5是NR7R7′的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R5 is NR7R7 ' .

在另一个实施方案中，本发明涉及其中没有R5是NR7R7′的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein none of R5 is NR7R7 ' .

在另一个实施方案中，本发明涉及其中一个R5是S-R8的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R 5 is SR 8 .

在另一个实施方案中，本发明涉及其中一个R5是SO2R8的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein one R5 is SO2R8 .

在另一个实施方案中，本发明涉及其中两个毗邻的R5与该芳族基团一起形成一种任选地包含一个或两个杂原子的5-8员环的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein two adjacent R 5 form together with the aromatic group a 5-8 membered ring optionally containing one or two heteroatoms.

在一个优选的实施方案中，本发明涉及其中两个毗邻的R5一起形成-(CH2)n′-CH2-、-CH＝CH-(CH2)m′-、-CH2-CH＝CH-(CH2)p′，-CH＝CH-CH＝CH-、-(CH2)n′-O-、-O-(CH2)m′-O-、-CH2-O-(CH2)p′-O-、-CH2-O-CH2-O-CH2-、-(CH2)n′-S-、-S-(CH2)m′-S-、-CH2-S-(CH2)p′-S-、-CH2-S-CH2-S-CH2-、-(CH2)n′-NH-、-NH-(CH2)m′-NH-、-CH2-NH-(CH2)p′-NH-、-CH＝CH-NH-、-O-(CH2)m′-NH-、-CH2-O-(CH2)p′-NH-或-O-(CH2)p′-NH-CH2-、-S-(CH2)m′-NH-、-N＝CH-NH-、-N＝CH-O-或-N＝CH-S-的式I的化合物，其中m′是1、2或3，n′是2、3或4和p′是1或2。In a preferred embodiment, the invention relates to wherein two adjacent R 5 together form -(CH 2 ) n' -CH 2 -, -CH═CH-(CH 2 ) m' -, -CH 2 -CH =CH-(CH 2 ) p' , -CH=CH-CH=CH-, -(CH 2 ) n' -O-, -O-(CH 2 ) m' -O-, -CH 2 -O- (CH 2 ) p′ -O-, -CH 2 -O-CH 2 -O-CH 2 -, -(CH 2 ) n′ -S-, -S-(CH 2 ) m′ -S-, - CH 2 -S-(CH 2 ) p′ -S-, -CH 2 -S-CH 2 -S-CH 2 -, -(CH 2 ) n′ -NH-, -NH-(CH 2 ) m′ -NH-, -CH 2 -NH-(CH 2 ) p′ -NH-, -CH═CH-NH-, -O-(CH 2 ) m′ -NH-, -CH 2 -O-(CH 2 ) p' -NH- or -O-(CH 2 ) p' -NH-CH 2 -, -S-(CH 2 ) m' -NH-, -N=CH-NH-, -N=CH-O A compound of formula I where m' is 1, 2 or 3, n' is 2, 3 or 4 and p' is 1 or 2 - or -N=CH-S-.

在另一个实施方案中，本发明涉及其中两个毗邻的R5一起形成-CH2-O-CH2-的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein two adjacent R5 are taken together to form -CH2 -O- CH2- .

在另一个实施方案中，本发明涉及其中两个毗邻的R5一起形成-CH＝CH-CH＝CH-的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein two adjacent R 5 are taken together to form -CH=CH-CH=CH-.

在另一个实施方案中，本发明涉及其中R7和R7′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基和C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to wherein R 7 and R 7′ are independently selected from hydrogen, C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl and Compounds of formula I that are C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及其中R7和R7′独立地选自氢和C1-6-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein R 7 and R 7′ are independently selected from hydrogen and C 1-6 -alk(en/yn)yl.

在另一个实施方案中，本发明涉及R7和R7′中的一个是C1-6-烷(链烯/炔)基，典型地是C1-3-烷(链烯/炔)基的式I的化合物。In another embodiment, the present invention relates to one of R 7 and R 7′ being C 1-6 -alk(en/yn)yl, typically C 1-3 -alk(en/yn)yl A compound of formula I.

在另一个实施方案中，本发明涉及其中R7和R7′都是C1-6-烷(链烯/炔)基，典型地是C1-3-烷(链烯/炔)基的式I的化合物。In another embodiment, the invention relates to wherein R 7 and R 7′ are both C 1-6 -alk(en/yn)yl, typically C 1-3 -alk(en/yn)yl A compound of formula I.

在另一个实施方案中，本发明涉及其中R8选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基和Ar的式I的化合物。In another embodiment, the present invention relates to wherein R 8 is selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cyclo Compounds of formula I of alk(en)yl-C 1-6 -alk(alken/yn)yl and Ar.

在一个优选的实施方案中，本发明涉其中R8选自C1-6-烷(链烯/炔)基和Ar的式I的化合物。In a preferred embodiment, the invention relates to compounds of formula I, wherein R 8 is selected from C 1-6 -alk(en/yn)yl and Ar.

在一个优选的实施方案中，本发明涉及其中R8是C1-6-烷(链烯/炔)基的式I的化合物。In a preferred embodiment, the invention relates to compounds of formula I, wherein R 8 is C 1-6 -alk(en/yn)yl.

在一个优选的实施方案中，本发明涉及其中R8是Ar的式I的化合物。In a preferred embodiment, the invention relates to compounds of formula I, wherein R 8 is Ar.

在另一个实施方案中，本发明涉及其中X是SO2，q是0和R3是C1-6-烷(链烯/炔)基，前提是R3不同于甲基的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein X is SO 2 , q is 0 and R 3 is C 1-6 -alk(en/yn)yl, provided that R 3 is different from methyl .

在另一个实施方案中，本发明涉及其中q是0，R3是甲基和X不同于SO2的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein q is 0, R3 is methyl and X is different from SO2 .

在另一个实施方案中，本发明涉及其中X是SO2，s是1和U不同于0的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein X is SO2 , s is 1 and U is different from zero.

在另一个实施方案中，本发明涉及其中s是1，U是O和X不同于SO2的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein s is 1, U is O and X is different from SO2 .

在另一个实施方案中，本发明涉及其中X是CO，q是0和R3是C1- 6-烷(链烯/炔)基，前提是R3不同于甲基的式I的化合物。In another embodiment, the invention relates to compounds of formula I, wherein X is CO, q is 0 and R 3 is C 1-6 -alk(en/yn)yl, provided that R 3 is different from methyl.

在另一个实施方案中，本发明涉及其中s是1，U不同于O，X是CO，q是0和R3是甲基的式I的化合物。In another embodiment, the invention relates to compounds of formula I wherein s is 1, U is different from O, X is CO, q is 0 and R3 is methyl.

在另一个实施方案中，本发明涉及其中s是1，U是O，X是CO，q是0和R3是C1-6-烷(链烯/炔)基，前提是R3不同于甲基的式I的化合物。In another embodiment, the invention relates to wherein s is 1, U is O, X is CO, q is 0 and R3 is C1-6 -alk(en/alkyn)yl, provided that R3 is different from A compound of formula I in which methyl is present.

本发明化合物的分子量可以随着化合物的不同而不同。式I化合物的分子量一般高于200并小于600，并且更一般地高于250并小于550。The molecular weight of the compounds of the invention may vary from compound to compound. Compounds of formula I generally have a molecular weight above 200 and below 600, and more typically above 250 and below 550.

本发明的一个方面涉及通式XXIX的化合物以及其盐：One aspect of the present invention relates to compounds of general formula XXIX and salts thereof:

Figure A20048000750700461
Figure A20048000750700461

其中f、s、q、U、X、Z、R1、R2、R3和R5的定义如上所述，f、s、q、U、X、Z、R1、R2、R3、R5、R6、R6′、R7、R7′、R8、R9、R9′、R10、R10′、R11、R12和R12′中的任何一个相应地具有式I下所定义的含义。式I涉及的任何一个实施方案也是式XXIX的实施方案。Wherein f, s, q, U, X, Z, R 1 , R 2 , R 3 and R 5 are defined as above, f, s, q, U, X, Z, R 1 , R 2 , R 3 , R 5 , R 6 , R 6′ , R 7 , R 7 ′ , R 8 , R 9 , R 9′ , R 10 , R 10′ , R 11 , R 12 and R 12′ correspondingly has the meaning defined under Formula I. Any of the embodiments referred to by formula I are also embodiments of formula XXIX.

在另一个实施方案中，本发明涉及其中f是0的通式XXIX的化合物。In another embodiment, the present invention is concerned with compounds of general formula XXIX, wherein f is 0.

在另一个实施方案中，本发明涉及被一个取代基R5取代的，如在邻-、间-或对-位上被取代的通式XXIX的化合物。In another embodiment, the invention relates to compounds of general formula XXIX substituted by one substituent R 5 , eg in the ortho-, meta- or para-position.

在另一个实施方案中，本发明涉及被两个独立进行选择的R5取代基取代的，如在邻-和对-位被取代、在间-和对-位被取代和在邻-和间-位被取代的通式XXIX的化合物。In another embodiment, the present invention relates to substituted by two independently selected R substituents, such as substituted at the ortho- and para-positions, substituted at the meta- and para-positions, and substituted at the ortho- and meta-positions. The compound of the general formula XXIX that - position is substituted.

在另一个实施方案中，本发明涉及被三个独立选择的R5取代基取代的通式XXIX的化合物。In another embodiment, the present invention is concerned with compounds of general formula XXIX substituted with three independently selected R substituents.

本发明另一方面涉及通式XXX的化合物或其盐：Another aspect of the present invention relates to compounds of general formula XXX or salts thereof:

Figure A20048000750700471
Figure A20048000750700471

其中g、h、s、q、U、X、Z、R1、R2、R3和R5的定义如上所述，g、h、s、q、U、X、Z、R1、R2、R3、R5、R6、R6′、R7、R7′、R8、R9、R9′、R10、R10′、R11、R12和R12′中的任何一个相应地具有式I下所定义的含义。式I涉及的任何一个实施方案也是式XXX的实施方案。Where g, h, s, q, U, X, Z, R 1 , R 2 , R 3 and R 5 are defined as above, g, h, s, q, U, X, Z, R 1 , R 2 , R 3 , R 5 , R 6 , R 6′ , R 7 , R 7′ , R 8 , R 9 , R 9′ , R 10 , R 10′ , R 11 , R 12 and R 12′ Any one has the meaning defined under formula I accordingly. Any of the embodiments referred to by formula I are also embodiments of formula XXX.

在一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到萘基的1位上的通式XXX的化合物。In one embodiment, the invention relates to compounds of general formula XXX wherein the nitrogen atom is attached to the 1-position of the naphthyl through a methylene group.

在另一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到萘基的2位上的通式XXX的化合物。In another embodiment, the invention relates to compounds of formula XXX wherein the nitrogen atom is attached to the 2-position of naphthyl through a methylene group.

在另一个实施方案中，本发明涉及其中g是0、1、2或3，典型地是0、1或2的通式XXX的化合物。In another embodiment, the invention relates to compounds of formula XXX wherein g is 0, 1 , 2 or 3, typically 0, 1 or 2.

在另一个实施方案中，本发明涉及其中h是0、1或2，典型地是0或1的通式XXX的化合物。In another embodiment, the invention relates to compounds of formula XXX wherein h is 0, 1 or 2, typically 0 or 1 .

在另一个实施方案中，本发明涉及其中g和h都是0的通式XXX的化合物。In another embodiment, the present invention is concerned with compounds of formula XXX wherein g and h are both zero.

在另一个实施方案中，本发明涉及被一个取代基R5取代的通式XXX的化合物，在其一个特定方面，g是0和h是1并且在其另一个特定方面，g是1和h是0。In another particular embodiment, the invention relates to compounds of general formula XXX substituted by one substituent R, in one particular aspect thereof g is 0 and h is 1 and in another particular aspect thereof g is 1 and h is 0.

在另一个实施方案中，本发明涉及被两个独立选择的R5取代基取代的通式XXX的化合物，在其一个特定方面，g是0和h是2，在其另一个特定方面，g是1和h是1并且在其另一个方面，g是2和h是0。In another particular embodiment, the invention relates to compounds of general formula XXX substituted by two independently selected R substituents, in one particular aspect thereof, g is 0 and h is 2, and in another particular aspect thereof, g is 1 and h is 1 and in another aspect thereof, g is 2 and h is 0.

在另一个实施方案中，本发明涉及被三个独立进行选择的R5取代基取代的通式XXX的化合物，在其一个特定方面，g是0和h是3，在其另一个特定方面，g是1和h是2，在其另一个方面g是2和h是1并且在其另一个方面，g是3和h是0。In another particular embodiment, the invention relates to compounds of formula XXX substituted with three independently selected R substituents, in one particular aspect thereof, g is 0 and h is 3, and in another particular aspect thereof, g is 1 and h is 2, in another aspect thereof g is 2 and h is 1 and in another aspect thereof, g is 3 and h is 0.

本发明另一方面涉及通式XXXI的化合物或其盐：

Figure A20048000750700481
Another aspect of the present invention relates to a compound of general formula XXXI or a salt thereof:
Figure A20048000750700481

其中a、s、q、U、W、X、Z、R1、R2、R3、和R5的定义如上所述，a、s、Z、R1、R2、R3、R5、R6、R6′、R7、R7′、R8、R9、R9′、R10、R10′、R11、R12和R12′中的任何一个相应地具有式I下所定义的含义。式I涉及的任何一个实施方案也是式XXXI的实施方案。Wherein a, s, q, U, W, X, Z, R 1 , R 2 , R 3 , and R 5 are as defined above, a, s, Z, R 1 , R 2 , R 3 , R 5 , R 6 , R 6′ , R 7 , R 7′ , R 8 , R 9 , R 9 ′ , R 10 , R 10′ , R 11 , R 12 and R 12′ correspondingly have formula I meaning defined below. Any of the embodiments referred to by formula I are also embodiments of formula XXXI.

在一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到该杂芳族基团2位上的通式XXXI的化合物。In one embodiment, the invention relates to compounds of general formula XXXI wherein the nitrogen atom is attached to the 2-position of the heteroaromatic group through a methylene group.

在另一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到该杂芳族基团3位上的通式XXXI的化合物。In another embodiment, the invention relates to compounds of formula XXXI wherein the nitrogen atom is attached to the heteroaromatic group at the 3-position via a methylene group.

在另一个实施方案中，本发明涉及其中a是0、1或2的通式XXXI的化合物。In another embodiment, the present invention is concerned with compounds of formula XXXI wherein a is 0, 1 or 2.

在另一个实施方案中，本发明涉及其中a是0的通式XXXI的化合物。In another embodiment, the present invention is concerned with compounds of formula XXXI wherein a is 0.

在另一个实施方案中，本发明涉及被一个取代基R5取代的通式XXXI的化合物。In another embodiment, the invention relates to compounds of general formula XXXI substituted with one substituent R 5 .

在另一个实施方案中，本发明涉及被两个独立进行选择的R5取代基取代的通式XXXI的化合物。In another embodiment, the present invention is concerned with compounds of general formula XXXI substituted with two independently selected R substituents.

本发明另一方面涉及通式XXXII的化合物或其盐：Another aspect of the present invention relates to a compound of general formula XXXII or a salt thereof:

Figure A20048000750700491
Figure A20048000750700491

其中b、c、s、q、U、W、X、Z、R1、R2、R3和R5的定义如上所述，b、c、s、q、U、W、X、Z、R1、R2、R3、R5、R6、R6′、R7、R7′、R8、R9、R9′、R10、R10′、R11、R12和R12′中的任何一个相应地具有式I下所定义的含义。式I涉及的任何一个实施方案也是式XXXII的实施方案。Wherein b, c, s, q, U, W, X, Z, R 1 , R 2 , R 3 and R 5 are defined as above, b, c, s, q, U, W, X, Z, R 1 , R 2 , R 3 , R 5 , R 6 , R 6 ′ , R 7 , R 7′ , R 8 , R 9 , R 9′ , R 10 , R 10′ , R 11 , R 12 and R Any one of 12' has the meaning defined under formula I accordingly. Any of the embodiments referred to by formula I are also embodiments of formula XXXII.

在一个实施方案中，本发明涉及其中氮原子通过亚甲基被被连接到该杂芳族基团2位上的通式XXXII的化合物。In one embodiment, the invention relates to compounds of general formula XXXII wherein the nitrogen atom is attached to the 2-position of the heteroaromatic group via a methylene group.

在另一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到该杂芳族基团的3位上的通式XXXII的化合物。In another embodiment, the invention relates to compounds of general formula XXXII, wherein the nitrogen atom is attached to the 3-position of the heteroaromatic group through a methylene group.

在另一个实施方案中，本发明涉及其中b是0、1、2或3，典型地是0、1或2的通式XXXII的化合物。In another embodiment, the invention relates to compounds of general formula XXXII wherein b is 0, 1, 2 or 3, typically 0, 1 or 2.

在另一个实施方案中，本发明涉及其中c是0或1，典型地是0的通式XXXII的化合物。In another embodiment, the invention relates to compounds of general formula XXXII wherein c is 0 or 1, typically 0.

在另一个实施方案中，本发明涉及其中b和c都是0的通式XXXII的化合物。In another embodiment, the present invention is concerned with compounds of general formula XXXII wherein b and c are both zero.

在另一个实施方案中，本发明涉及被一个取代基R5取代的通式XXXII的化合物，在其一个方面，b是0和c是1并且在其另一个方面，b是1和c是0。In another embodiment, the present invention relates to compounds of general formula XXXII substituted by one substituent R, in one aspect thereof, b is 0 and c is 1 and in another aspect thereof , b is 1 and c is 0 .

在另一个实施方案中，本发明涉及被两个独立进行选择的R5取代基取代的通式XXXII的化合物，在其一个方面，b是1和c是1并且在其另一个方面，b是2和c是0。In another embodiment, the invention relates to compounds of formula XXXII substituted by two independently selected R substituents, in one aspect thereof, b is 1 and c is 1 and in another aspect thereof, b is 2 and c are 0.

在另一个实施方案中，本发明涉及被三个独立进行选择的R5取代基取代的通式XXXII的化合物，在其一个方面，b是2和c是1并且在其另一个方面，b是3和c是0。In another embodiment, the invention relates to compounds of formula XXXII substituted by three independently selected R substituents, in one aspect thereof, b is 2 and c is 1 and in another aspect thereof, b is 3 and c are 0.

本发明另一方面涉及通式XXXIII的化合物或其盐：Another aspect of the present invention relates to compounds of general formula XXXIII or salts thereof:

Figure A20048000750700501
Figure A20048000750700501

其中d、e、s、q、U、W、X、Z、R1、R2、R3和R5的定义如上所述，d、e、s、q、U、W、X、Z、R1、R2、R3、R5、R6、R6′、R7、R7′、R8、R9、R9′、R10、R10′、R11、R12和R12′中的任何一个相应地具有式I下所定义的含义。式I涉及的任何一个实施方案也是式XXXIII的方案。Wherein d, e, s, q, U, W, X, Z, R 1 , R 2 , R 3 and R 5 are defined as above, d, e, s, q, U, W, X, Z, R 1 , R 2 , R 3 , R 5 , R 6 , R 6 ′ , R 7 , R 7′ , R 8 , R 9 , R 9′ , R 10 , R 10′ , R 11 , R 12 and R Any one of 12' has the meaning defined under formula I accordingly. Any one of the embodiments referred to by formula I is also a solution of formula XXXIII.

在一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到该杂芳族基团4位上的通式XXXIII的化合物。In one embodiment, the invention relates to compounds of general formula XXXIII wherein the nitrogen atom is attached to the 4-position of the heteroaromatic group via a methylene group.

在另一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到该杂芳族基团5位上的通式XXXIII的化合物。In another embodiment, the invention relates to compounds of general formula XXXIII wherein the nitrogen atom is attached to the 5-position of the heteroaromatic group via a methylene group.

在一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到该杂芳族基团6位上的通式XXXIII的化合物。In one embodiment, the invention relates to compounds of general formula XXXIII wherein the nitrogen atom is attached to the 6-position of the heteroaromatic group via a methylene group.

在另一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到该杂芳族基团7位上的通式XXXIII的化合物。In another embodiment, the invention relates to compounds of general formula XXXIII, wherein the nitrogen atom is attached to the 7-position of the heteroaromatic group through a methylene group.

在另一个实施方案中，本发明涉及其中d是0、1或2，典型地是0或1通式XXXIII的化合物。In another embodiment, the invention relates to compounds of general formula XXXIII wherein d is 0, 1 or 2, typically 0 or 1.

在另一个实施方案中，本发明涉及其中e是0、1或2的通式XXXIII的化合物。In another embodiment, the present invention is concerned with compounds of general formula XXXIII wherein e is 0, 1 or 2.

在另一个实施方案中，本发明涉及其中d和e都是0的通式XXXIII的化合物。In another embodiment, the present invention is concerned with compounds of general formula XXXIII wherein d and e are both zero.

在另一个实施方案中，本发明涉及被一个取代基R5取代的通式XXXIII的化合物，在其一个特定方面，d是0并且e是1和在其另一个特定方面，d是1和e是0。In another particular embodiment, the invention relates to compounds of general formula XXXIII substituted by one substituent R, in one particular aspect thereof, d is 0 and e is 1 and in another particular aspect thereof, d is 1 and e is 0.

在另一个实施方案中，本发明涉及被两个独立选择的R5取代基取代的通式XXXIII的化合物，在其一个特定方面，d是0和e是2，在其另一个特定方面，d是1和e是1并且在其另一个方面，d是2和e是0。In another particular embodiment, the invention relates to compounds of general formula XXXIII substituted by two independently selected R substituents, in one particular aspect thereof, d is 0 and e is 2, and in another particular aspect thereof, d is 1 and e is 1 and in another aspect thereof, d is 2 and e is 0.

在另一个实施方案中，本发明涉及被三个独立选择的R5取代基取代的通式XXXIII的化合物，在其一个方面，d是1和e是2，在其另一个方面，d是2和e是1并且在其另一个方面，d是3和e是0。In another embodiment, the invention relates to a compound of formula XXXIII substituted by three independently selected R substituents, in one aspect thereof, d is 1 and e is 2, in another aspect thereof, d is 2 and e are 1 and in another aspect thereof, d is 3 and e is 0.

本发明另一方面涉及通式XXXXIII的化合物或其盐：Another aspect of the present invention relates to a compound of general formula XXXXIII or a salt thereof:

其中dd、s、q、U、V、X、Z、R1、R2、R3和R5具有式I下所定义的含义。式I涉及的任何一个实施方案也是式XXXXIII的实施方案。wherein dd, s, q, U, V, X, Z, R 1 , R 2 , R 3 and R 5 have the meanings defined under formula I. Any of the embodiments referred to by formula I are also embodiments of formula XXXXIII.

在另一个实施方案中，本发明涉及其中V是氮原子通过亚甲基连接于其上的碳原子的通式XXXIII的化合物。In another embodiment, the invention is concerned with compounds of general formula XXXIII wherein V is a carbon atom to which the nitrogen atom is attached via a methylene group.

在一个实施方案中，本发明涉其中氮原子通过亚甲基被连接到被标为“1”的碳原子上的通式XXXXIII的化合物。In one embodiment, the invention relates to compounds of general formula XXXXIII wherein the nitrogen atom is attached to the carbon atom designated "1" through a methylene group.

在一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到被标为“2”的碳原子上的通式XXXXIII的化合物。In one embodiment, the invention relates to compounds of general formula XXXXIII wherein the nitrogen atom is attached to the carbon atom designated "2" through a methylene group.

在另一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到被标为“3”的碳原子上的通式XXXXIII的化合物。In another embodiment, the invention is concerned with compounds of general formula XXXXIII wherein the nitrogen atom is attached to the carbon atom designated "3" through a methylene group.

在另一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到被标为“4”的碳原子上的通式XXXXIII的化合物。In another embodiment, the invention is concerned with compounds of general formula XXXXIII wherein the nitrogen atom is attached to the carbon atom designated "4" through a methylene group.

在另一个实施方案中，本发明涉及其中dd是0、1或2，典型地是0或1的通式XXXXIII的化合物。在本发明的一个方面，dd是0。在本发明的另一个方面，dd是0。In another embodiment, the invention relates to compounds of general formula XXXXIII wherein dd is 0, 1 or 2, typically 0 or 1 . In one aspect of the invention, dd is zero. In another aspect of the invention, dd is zero.

本发明另一方面涉及通式XXXXIV的化合物或其盐：Another aspect of the present invention relates to a compound of general formula XXXXIV or a salt thereof:

Figure A20048000750700521
Figure A20048000750700521

其中aa、s、q、T、U、X、Z、R1、R2、R3和R5具有式I下所定义的含义。式I涉及的任何一个实施方案也是式XXXXIV的化合物。wherein aa, s, q, T, U, X, Z, R 1 , R 2 , R 3 and R 5 have the meanings defined under formula I. Any of the embodiments referred to by formula I are also compounds of formula XXXXIV.

在一个实施方案中，本发明涉及其中T是氮原子通过亚甲基连接于其上的氮原子的通式XXXXIV的化合物。In one embodiment, the invention relates to compounds of general formula XXXXIV wherein T is a nitrogen atom to which the nitrogen atom is attached via a methylene group.

在一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到被标为“1”的碳原子上的通式XXXXIV的化合物。In one embodiment, the invention is concerned with compounds of general formula XXXXIV wherein the nitrogen atom is attached to the carbon atom designated "1" through a methylene group.

在一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到被标为“2”的碳原子上的通式XXXXIV的化合物。In one embodiment, the invention is concerned with compounds of general formula XXXXIV wherein the nitrogen atom is attached to the carbon atom designated "2" through a methylene group.

在另一个实施方案中，本发明涉及其中氮原子通过亚甲基被连接到被标为“3”的碳原子上的通式XXXXIV的化合物。In another embodiment, the invention is concerned with compounds of general formula XXXXIV wherein the nitrogen atom is attached to the carbon atom designated "3" through a methylene group.

在另一个实施方案中，本发明涉及其中aa是0、1或2的通式XXXI的化合物。在一个实施方案中，aa是0。在另一个实施方案中，通式XXXXIV被一个取代基R5所取代。在另一个实施方案中，通式XXXI的化合物被两个独立选择的R5取代基所取代。In another embodiment, the present invention is concerned with compounds of formula XXXI wherein aa is 0, 1 or 2. In one embodiment, aa is 0. In another embodiment, formula XXXXIV is substituted with one substituent R 5 . In another embodiment, the compound of formula XXXI is substituted with two independently selected R substituents.

在一个特定的实施方案中，本发明涉及通式Ia的被取代的对-二氨基苯衍生物或其盐In a particular embodiment, the present invention relates to substituted p-diaminobenzene derivatives of general formula Ia or salts thereof

Figure A20048000750700522
Figure A20048000750700522

其中in

s是0或1；s is 0 or 1;

U是O、S、SO2、SO2NR11、CO-O或CO-NR11；其中R11选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C6-烷(链烯/炔)基；或R2和R11与该氮原于一起形成一种任选地包含1、2或3个另外的杂原子的5-8员饱和或不饱和的环；U is O, S, SO 2 , SO 2 NR 11 , CO-O or CO-NR 11 ; wherein R 11 is selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -ring Alk(en)yl, C 3-8 -cycloalk(en)yl-C6-alk(alkene/alkyn)yl; or R and R together with the nitrogen form a compound optionally comprising 5-8 membered saturated or unsaturated rings with 1, 2 or 3 additional heteroatoms;

q是0或1；q is 0 or 1;

X是CO或SO2；前提是当X是SO2时q是0；X is CO or SO2 ; provided that q is 0 when X is SO2 ;

Z是O或S；Z is O or S;

R1选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、酰基、羟基-C1-6-烷(链烯/炔)基、羟基-C1-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基和氰基-C3-8-环烷(链烯)基-C6-烷(链烯/炔)基；R 1 is selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(alkene/alkyn)yl, acyl, hydroxy-C 1-6 -alk(en/alkyn)yl, hydroxy-C1-8-cycloalkane(en)yl, hydroxy-C 3-8 -cyclo Alk(en)yl-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl, halo-C 3-8 -cycloalkane(alkyn) alken)yl, halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, cyano-C 1-6 -alk(en/alkyn)yl , cyano-C 3-8 -cycloalk(en)yl and cyano-C 3-8 -cycloalk(en)yl-C6-alk(en/alkyn)yl;

R2选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、酰基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤素、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基、氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、NR10R10′-C1-6-烷(链烯/炔)基、NR10R10′-C3-8-环烷(链烯)基和NR10R10′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基；其中R10和R10′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-CI6-烷(链烯/炔)基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基和氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基，或R10和R10′和其与之相连的氮原子一起形成一种任选地包含1、2或3个另外的杂原子的5-8员饱和或不饱和的环；R 2 is selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -Alk(en/alkyn)yl, Ar, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3-8 -cycloalk(en)yl, Ar-C 3-8- Cycloalk(en)yl-C 1-6 -alk(alkene/alkyn)yl, acyl, hydroxy-C 1-6 -alk(en/alkyn)yl, hydroxy-C 3-8 -cycloalkane( Alken) group, hydroxy-C 3-8 -cycloalk(en) group-C 1-6 -alk(alkene/alkynyl) group, halogen, halo-C 1-6 -alk(alkene/alkyne) group ) group, halo-C 3-8 -cycloalk(alkene) group, halo-C 3-8 -cycloalk(alkene) group-C 1-6 -alk(alkene/alkyne) group, cyanide Cyano-C 1-6 -alk(en/alkyn)yl, cyano-C 3-8 -cycloalk(en)yl, cyano-C 3-8 -cycloalk(en)yl -C 1-6 -alk(en/alkyn)yl, NR 10 R 10′ -C 1-6 -alk(en/alkyn)yl, NR 10 R 10′ -C 3-8 -cycloalkane(alkynyl) alken) group and NR 10 R 10′ -C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn) group; wherein R 10 and R 10′ are independently selected from hydrogen, C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-CI6-alk(en/yn)yl , Hydroxy-C 1-6 -alk(en/alkyn)yl, Hydroxy-C 3-8 -cycloalk(en)yl, Hydroxy-C 3-8 -cycloalk(en)yl-C 1- 6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl, halo-C 3-8 -cycloalk(en)yl, halo-C 3- 8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, cyano-C 1-6 -alk(en/alkyn)yl, cyano-C 3-8 -cyclo Alk(en)yl and cyano-C 3-8 -cycloalk(en)yl-C 1-6 -alk(alken/alkyn)yl, or R 10 and R 10' and their attached The nitrogen atoms together form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms;

前提是当R2是卤素或氰基时，s是0；和provided that when R2 is halo or cyano, s is 0; and

前提是当s是1和R2是氢原子或酰基时，U是O或S。Provided that U is O or S when s is 1 and R2 is a hydrogen atom or an acyl group.

R3选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、杂环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)基-C1-6-环烷(链烯)基、C1-6-烷(链烯/炔)基-杂环烷(链烯)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-杂环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、Ar-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)氧基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-C3-8-环烷(链烯)基、C1-6-烷(链烯/炔)氧基-杂环烷(链烯)基、Ar-氧基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)氧基-羰基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-杂环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、羟基-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、羟基-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-杂环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基-Ar、卤代-C3-8-环烷(链烯)基-Ar、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基-Ar、卤代-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基-Ar、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基、氰基-杂环烷(链烯)基、氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、氰基-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、酰基-C1-6-烷(链烯/炔)基、酰基-C3-8-环烷(链烯)基、酰基-杂环烷(链烯)基、酰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、酰基-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、酰基-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、-NR12R12′；其中R12和R12′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基和氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基，或R12和R12′和其与之相连的氮原子一起形成一种任选地包含1、2或3个另外的杂原子的5-8员饱和或不饱和的环；R 3 is selected from C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, heterocycloalk(en)yl, C 3-8 -cycloalk(en)yl ) group-C 1-6 -alk(en/alkyn)yl, C 1-6 -alk(en/alkyn)yl-C 1-6 -cycloalk(en)yl, C 1-6 -alk (Alken/Alkyn)yl-Heterocycloalkan(en)yl, Ar, Ar-C 1-6 -Alk(en/Alkyn)yl, Ar-C 3-8 -Cycloalk(en)yl, Ar-heterocycloalkan(en)yl, Ar-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, Ar-C 1-6 -alk(alkene) En/alkyn)yl-C 3-8 -cycloalk(en)yl, Ar-C 1-6 -alk(en/alkyn)yl-heterocycloalk(en)yl, C 1-6 -alk (alkene/alkynyl)oxy-C 1-6 -alk(en/alkynyl)yl, C 3-8 -cycloalkane(alkenyl)oxy-C 1-6 -alk(en/alkynyl)yl , C 1-6 -alk(alkene/alkyne)oxy-C 3-8 -cycloalkane(en)yl, C 1-6 -alk(alkene/alkyne)oxy-heterocycloalkane(alkene ) group, Ar-oxy-C 1-6 -alk(alkene/alkyne)yl, Ar-C 1-6 -alk(alkene/alkyne)oxy-C 1-6 -alk(alkene/alkyne) ) group, C 1-6 -alk(alkene/alkyne)oxy-carbonyl-C 1-6 -alk(alkene/alkynyl)yl, C 3-8 -cycloalkane(alkene)oxy-carbonyl- C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)oxy-carbonyl-C 1-6 -alk (alkene/alkyne)yl, hydroxy-C 1-6 -alk(alkene/alkyne)yl, hydroxy-C 3-8 -cycloalkane(alkene)yl, hydroxy-heterocycloalkane(alkene)yl, Hydroxy-C 3-8 -Cycloalkane(alkene)yl-C 1-6 -Alk(alkene/alkyne)yl, Hydroxy-C 1-6 -Alk(alkene/alkynyl)yl-C 3-8- Cycloalk(en)yl, Hydroxy-C 1-6 -alk(en/yn)yl-heterocycloalk(en)yl, Halo-C 1-6 -alk(en/yn)yl, Halo-C 3-8 -cycloalk(en)yl, halo-heterocycloalk(en)yl, halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk (alkene/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(alkene)yl, halo-C 1-6 -alk(alkene) /alkyn)yl-heterocycloalkane(alkene)yl, halo-C 1-6 -alk(alkene/alkyn)yl-Ar, halo-C 3-8 -cycloalkane(alkene)yl-Ar , Halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl-Ar, halo-C 1-6 -alk(en/alkyn)yl- C 3-8 -cycloalk(en)yl-Ar, cyano-C 1-6 -alk(en/alkyn)yl, cyano-C 3-8 -cycloalk(en)yl, cyano -heterocycloalkan(en)yl, cyano-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, cyano-C 1-6 -alk( Alken/alkyn)yl-C 3-8 -cycloalk(en)yl, cyano-C 1-6 -alk(en/alkyn)yl-heterocycloalk(alken)yl, acyl-C 1 -6 -alk(en/alkyn)yl, acyl-C 3-8 -cycloalk(en)yl, acyl-heterocycloalk(en)yl, acyl-C 3-8 -cycloalk(en)yl ) group-C 1-6 -alk(en/alkyn)yl, acyl-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(en)yl, acyl-C 1 -6 -alk(en/alkyn)yl-heterocycloalk(en)yl, -NR 12 R 12' ; wherein R 12 and R 12' are independently selected from hydrogen, C 1-6 -alk(alkene) /alkynyl) group, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, hydroxyl-C 1- 6 -alk(en/alkyn)yl, hydroxy-C 3-8 -cycloalk(en)yl, hydroxy-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en) /alkyn) group, halo-C 1-6 -alk(alkene/alkyn)yl, halo-C 3-8 -cycloalk(en)yl, halo-C 3-8 -cycloalkane(chain Alken)yl-C 1-6 -alk(alkene/alkynyl)yl, cyano-C 1-6 -alk(en/alkynyl)yl, cyano-C 3-8 -cycloalkalk(en)yl and cyano-C 3-8 -cycloalk(en)yl-C 1-6 -alk(alkene/alkyn)yl, or R 12 and R 12' together with the nitrogen atom to which they are attached form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms;

和and

Y表示式XXIV、XXV、XXVI、XXVII或XXVIII的基团：Y represents a group of formula XXIV, XXV, XXVI, XXVII or XXVIII:

其中in

该线表示一种将Y所示的基团连接到该碳原子上的键；The line represents a bond connecting the group represented by Y to the carbon atom;

W是O或S；W is O or S;

A是0、1、2或3；A is 0, 1, 2 or 3;

b是0、1、2、3或4；b is 0, 1, 2, 3 or 4;

c是0或1；c is 0 or 1;

d是0、1、2或3；d is 0, 1, 2 or 3;

e是0、1或2；e is 0, 1 or 2;

f是0、1、2、3、4或5；f is 0, 1, 2, 3, 4 or 5;

g是0、1、2、3或4；g is 0, 1, 2, 3 or 4;

h是0、1、2或3；和h is 0, 1, 2 or 3; and

各R5独立地选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar、Ar-C1-6-烷(链烯/炔)基、酰基、C1-6-烷(链烯/炔)氧基、C3-8-环烷(链烯)氧基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)氧基、卤素、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、-CO-NR6R6′、氰基、氰基-C1-6-烷(链烯/炔)基、氰基C3-8-环烷(链烯)基、氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、NR7R7′、S-R8和-SO2R8，或者两个毗邻的R5与该芳族基团一起形成一种包含一个或两个杂原子的5-8员环；Each R 5 is independently selected from C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1- 6 -alk(en/alkyn)yl, Ar, Ar-C 1-6 -alk(en/alkyn)yl, acyl, C 1-6 -alk(en/alkyn)oxy, C 3-8 -cycloalk(alkene)oxy, C 3-8 -cycloalk(en)yl-C 1-6 -alk(alkene/alkyne)oxy, halogen, halo-C 1-6 -alk( Alken/alkynyl) group, halo-C 3-8 -cycloalk(en)yl, halo-C 3-8 -cycloalk(alken)yl-C 1-6 -alk(alken/alkyne ) group, -CO-NR 6 R 6′ , cyano, cyano-C 1-6 -alk(alkene/alkyne) group, cyano C 3-8 -cycloalkane(alkene) group, cyano- C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, NR 7 R 7' , SR 8 and -SO 2 R 8 , or two adjacent R 5 with The aromatic groups together form a 5-8 membered ring containing one or two heteroatoms;

R6和R6′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基和Ar；R 6 and R 6′ are independently selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl -C 1-6 -alk(alkene/alkyn)yl and Ar;

R7和R7′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar和酰基；和R 7 and R 7′ are independently selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl -C 1-6 -alk(en/alkyn)yl, Ar and acyl; and

R8选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar和-NR9R9′；其中R9和R9′独立地选自氢、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基和C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基。R 8 is selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -Alk(en/alkyn)yl, Ar and -NR 9 R 9' ; wherein R 9 and R 9' are independently selected from hydrogen, C 1-6 -alk(en/alkyn)yl, C 3-8 - cycloalk(en)yl and C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl.

在一个实施方案中，优选下面列出的化合物以及其盐：In one embodiment, the compounds listed below and their salts are preferred:

{4-[(苯并呋喃-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(Benzofuran-2-ylmethyl)-amino]-2-methylphenyl}-propyl carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamate ethyl ester;

{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸乙酯；{4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamate ethyl ester;

{2-甲基-4-[(5-苯基-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸乙酯；{2-Methyl-4-[(5-phenyl-thiophen-2-ylmethyl)-amino]-phenyl}-urethane;

[4-(4-异丙基-苄基氨基)-2-甲基苯基]-氨基甲酸乙酯；[4-(4-Isopropyl-benzylamino)-2-methylphenyl]-ethyl carbamate;

[4-(4-氟-苄基氨基)-2-甲基苯基]-氨基甲酸丙酯；[4-(4-Fluoro-benzylamino)-2-methylphenyl]-propyl carbamate;

(4-{[4-(4-氯-苯磺酰基)-3-甲基-噻吩-2-基甲基]-氨基}-2-甲基苯基)-氨基甲酸丙酯；(4-{[4-(4-Chloro-benzenesulfonyl)-3-methyl-thiophen-2-ylmethyl]-amino}-2-methylphenyl)-propyl carbamate;

{4-[(5-甲基-噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(5-Methyl-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-propyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-propyl carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-propyl carbamate;

{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-propyl carbamate;

{2-甲基-4-[(5-苯基-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{2-Methyl-4-[(5-phenyl-thiophen-2-ylmethyl)-amino]-phenyl}-propyl carbamate;

[4-(4-异丙基-苄基氨基)-2-甲基苯基]-氨基甲酸丙酯；[4-(4-Isopropyl-benzylamino)-2-methylphenyl]-propyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸乙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-ethyl carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-ethyl carbamate;

{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸乙酯；{4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-ethyl carbamate;

[2-氯-4-(4-异丙基-苄基氨基)-苯基]-氨基甲酸乙酯；[2-Chloro-4-(4-isopropyl-benzylamino)-phenyl]-carbamate ethyl ester;

[2-氯-4-(4-氟-苄基氨基)-苯基]-氨基甲酸丙酯；[2-Chloro-4-(4-fluoro-benzylamino)-phenyl]-carbamate propyl ester;

2-氯-4-{[4-(4-氯-苯磺酰基)-3-甲基-噻吩-2-基甲基]-氨基}-苯基)-氨基甲酸丙酯；2-Chloro-4-{[4-(4-chloro-benzenesulfonyl)-3-methyl-thiophen-2-ylmethyl]-amino}-phenyl)-propyl carbamate;

{4-[(5-甲基-噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸丙酯；{4-[(5-Methyl-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-propyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-propyl carbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-propyl carbamate;

{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸丙酯；{4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-propyl carbamate;

{4-[(苯并呋喃-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸丙酯；{4-[(benzofuran-2-ylmethyl)-amino]-2-chlorophenyl}-propyl carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-氰基苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-cyanophenyl}-ethyl carbamate;

{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-甲氧基苯基}-氨基甲酸甲酯；{4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-methyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-甲氧基苯基}-氨基甲酸异丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-carbamate isopropyl ester;

{4-[(4-氟-苄基)-(甲基)氨基]-2-甲氧基苯基}-氨基甲酸丙酯；{4-[(4-Fluoro-benzyl)-(methyl)amino]-2-methoxyphenyl}-propyl carbamate;

{4-(苯并[b]噻吩-2-基甲基-(甲基)氨基)-2-甲氧基-苯基}-氨基甲酸丙酯；Propyl {4-(benzo[b]thiophen-2-ylmethyl-(methyl)amino)-2-methoxy-phenyl}-carbamate;

{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲氧基-苯基}-氨基甲酸丙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methoxy-phenyl}-carbamic acid propyl ester;

{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-甲氧基-苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-methoxy-phenyl}-propyl carbamate;

{2-甲氧基-4-[甲基-(5-甲基-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{2-Methoxy-4-[methyl-(5-methyl-thiophen-2-ylmethyl)-amino]-phenyl}-propyl carbamate;

{4-[(4-氟苄基)-(甲基)-氨基]-2-异丙氧基苯基}-氨基甲酸乙酯；{4-[(4-fluorobenzyl)-(methyl)-amino]-2-isopropoxyphenyl}-ethyl carbamate;

[4-(3-氟苄基氨基)-2-甲氧基苯基]-氨基甲酸乙酯；[4-(3-Fluorobenzylamino)-2-methoxyphenyl]-ethyl carbamate;

[4-(4-异丙基苄基氨基)-2-甲氧基苯基]-氨基甲酸乙酯；[4-(4-Isopropylbenzylamino)-2-methoxyphenyl]-ethyl carbamate;

{2-甲氧基-4-[(3-甲基噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸乙酯；{2-Methoxy-4-[(3-methylthiophen-2-ylmethyl)-amino]-phenyl}-urethane;

[4-(2，4-二氟苄基氨基)-2-甲氧基苯基]-氨基甲酸乙酯；[4-(2,4-Difluorobenzylamino)-2-methoxyphenyl]-ethyl carbamate;

[2-环戊氧基-4-(4-甲氧基苄基氨基)-苯基]-氨基甲酸乙酯；[2-Cyclopentyloxy-4-(4-methoxybenzylamino)-phenyl]-carbamate ethyl ester;

[2-环戊氧基-4-(3-氟-2-甲基苄基氨基)-苯基]-氨基甲酸乙酯；[2-Cyclopentyloxy-4-(3-fluoro-2-methylbenzylamino)-phenyl]-urethane;

[4-(3-氟-2-甲基苄基氨基)-2-苯乙氧基苯基]-氨基甲酸乙酯；[4-(3-Fluoro-2-methylbenzylamino)-2-phenethoxyphenyl]-ethyl carbamate;

[2-苄氧基-4-(3-氟-2-甲基苄基氨基)-苯基]-氨基甲酸乙酯；[2-Benzyloxy-4-(3-fluoro-2-methylbenzylamino)-phenyl]-carbamate ethyl ester;

[2-苄氧基-4-(4-甲基硫烷基苄基氨基)-苯基]-氨基甲酸乙酯；[2-Benzyloxy-4-(4-methylsulfanylbenzylamino)-phenyl]-ethyl carbamate;

{4-[(苯并[b]噻吩-3-基甲基)-氨基]-2-环戊氧基苯基}-氨基甲酸乙酯；{4-[(Benzo[b]thiophen-3-ylmethyl)-amino]-2-cyclopentyloxyphenyl}-ethyl carbamate;

[4-(3-氟-2-甲基苄基氨基)-2-异丙氧基苯基]-氨基甲酸乙酯；[4-(3-Fluoro-2-methylbenzylamino)-2-isopropoxyphenyl]-ethyl carbamate;

[2-苄氧基-4-(3-甲氧基苄基氨基)-苯基]-氨基甲酸乙酯；[2-Benzyloxy-4-(3-methoxybenzylamino)-phenyl]-ethyl carbamate;

{4-[(苯并[1，3]间二氧杂环戊烯-5-基甲基)-氨基]-2-异丙氧基苯基}-氨基甲酸乙酯；{4-[(Benzo[1,3]dioxol-5-ylmethyl)-amino]-2-isopropoxyphenyl}-urethane;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-phenyl}-carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-phenyl}-carbamate;

[2-氰基-4-(4-异丙基苄基氨基)-苯基]-氨基甲酸乙酯；[2-cyano-4-(4-isopropylbenzylamino)-phenyl]-carbamate ethyl ester;

{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-propyl carbamate;

{4-[(4-异丙基苄基)-(甲基)氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(4-isopropylbenzyl)-(methyl)amino]-2-methylphenyl}-propyl carbamate;

{2-甲基-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸丙酯；{2-Methyl-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-propyl carbamate;

{2-甲基-4-[甲基-(4-甲基硫烷基-苄基)-氨基]-苯基}-氨基甲酸丙酯；{2-Methyl-4-[methyl-(4-methylsulfanyl-benzyl)-amino]-phenyl}-propyl carbamate;

{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-氯苯基}-氨基甲酸乙酯；{4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-chlorophenyl}-ethyl carbamate;

{2-氯-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸乙酯；{2-Chloro-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-carbamate ethyl ester;

{2-氯-4-[甲基-(4-甲基硫烷基-苄基)-氨基]-苯基}-氨基甲酸乙酯；{2-Chloro-4-[methyl-(4-methylsulfanyl-benzyl)-amino]-phenyl}-ethyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-氯苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-chlorophenyl}-propyl carbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丙酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester;

{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-氯苯基}-氨基甲酸丙酯；{4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-chlorophenyl}-propyl carbamate;

{2-氯-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸丙酯；{2-Chloro-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-propyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-三氟甲基-苯基}氨基甲酸乙酯；Ethyl {4-[(5-bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}carbamate;

{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamate ethyl ester;

{4-[(4-异丙基-苄基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[(4-Isopropyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-ethyl carbamate;

{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-ethyl carbamate;

{4-[甲基-(4-三氟甲基-苄基)-氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[Methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-ethyl carbamate;

{4-[甲基-(4-甲基硫烷基-苄基)-氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[Methyl-(4-methylsulfanyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-ethyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester;

{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester;

{4-[(4-异丙基-苄基)-(甲基)氨基]-2-三氟甲基-苯基}-基甲酸丙酯；Propyl {4-[(4-isopropyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-ylformate;

{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-propyl carbamate;

{4-[甲基-(4-三氟甲基-苄基)-氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[Methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-propyl carbamate;

{4-[甲基-(4-甲基硫烷基-苄基)-氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[Methyl-(4-methylsulfanyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-propyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-氰基苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-cyanophenyl}-propyl carbamate;

{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-氰基苯基}-氨基甲酸丙酯；{4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-cyanophenyl}-propyl carbamate;

{2-氰基-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸丙酯；{2-cyano-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-propyl carbamate;

{2-溴-4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丙酯；{2-bromo-4-[(5-bromo-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamate;

{2-溴-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丙酯；{2-Bromo-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester;

{2-溴-4-[(4-异丙基苄基)-(甲基)氨基]-苯基}-氨基甲酸丙酯；{2-Bromo-4-[(4-isopropylbenzyl)-(methyl)amino]-phenyl}-carbamate;

{2-溴-4-[(4-叔-丁基-苄基)-(甲基)氨基]-苯基}-氨基甲酸丙酯；{2-Bromo-4-[(4-tert-butyl-benzyl)-(methyl)amino]-phenyl}-propyl carbamate;

{2-溴-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸丙酯；{2-Bromo-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-propyl carbamate;

[2-碘-4-(4-异丙基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-iodo-4-(4-isopropyl-benzylamino)-phenyl]-carbamate;

[4-(4-叔-丁基-苄基氨基)-2-碘苯基]-氨基甲酸丙酯；[4-(4-tert-butyl-benzylamino)-2-iodophenyl]-propyl carbamate;

[2-碘-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-iodo-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamate propyl ester;

[2-碘-4-(4-甲基硫烷基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-iodo-4-(4-methylsulfanyl-benzylamino)-phenyl]-carbamate propyl ester;

{2-碘-4-[4-(4-甲基哌嗪-1-基)-苄基氨基]-苯基}-氨基甲酸丙酯；{2-iodo-4-[4-(4-methylpiperazin-1-yl)-benzylamino]-phenyl}-carbamic acid propyl ester;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl}-carbamate ethyl ester;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl}-carbamate ethyl ester;

[4-(4-叔-丁基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸乙酯；[4-(4-tert-butyl-benzylamino)-2-trifluoromethyl-phenyl]-ethyl carbamate;

[4-(4-甲基硫烷基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸乙酯；[4-(4-Methylsulfanyl-benzylamino)-2-trifluoromethyl-phenyl]-ethyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl}-propyl carbamate;

[4-(4-异丙基苄基氨基)-2-三氟甲基-苯基]-氨基甲酸丙酯；[4-(4-Isopropylbenzylamino)-2-trifluoromethyl-phenyl]-propyl carbamate;

[4-(4-叔-丁基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸丙酯；[4-(4-tert-butyl-benzylamino)-2-trifluoromethyl-phenyl]-propyl carbamate;

[2-三氟甲基-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-Trifluoromethyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid propyl ester;

[4-(4-二甲基氨基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸丙酯；[4-(4-Dimethylamino-benzylamino)-2-trifluoromethyl-phenyl]-propyl carbamate;

[4-(4-甲基硫烷基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸丙酯；[4-(4-Methylsulfanyl-benzylamino)-2-trifluoromethyl-phenyl]-propyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-氰基苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-cyanophenyl}-propyl carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-氰基苯基}-氨基甲酸丙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-cyanophenyl}-propyl carbamate;

[2-氰基-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-cyano-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamate propyl ester;

{2-溴-4-[(5-溴-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{2-bromo-4-[(5-bromo-thiophen-2-ylmethyl)-amino]-phenyl}-propyl carbamate;

{2-溴-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{2-Bromo-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-propyl carbamate;

[2-溴-4-(4-异丙基苄基氨基)-苯基J-氨基甲酸丙酯；[2-Bromo-4-(4-isopropylbenzylamino)-phenyl J-propyl carbamate;

[2-溴-4-(4-叔-丁基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-Bromo-4-(4-tert-butyl-benzylamino)-phenyl]-carbamate propyl ester;

[2-溴-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-Bromo-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid propyl ester;

[2-溴-4-(4-甲基硫烷基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-Bromo-4-(4-methylsulfanyl-benzylamino)-phenyl]-carbamate propyl ester;

N-{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-甲氧基苯基}-丁酰胺；N-{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-butanamide;

N-{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-甲氧基苯基)-丁酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-methoxyphenyl)-butanamide;

N-[4-(4-异丙基苄基氨基)-2-甲氧基苯基]-丁酰胺；N-[4-(4-isopropylbenzylamino)-2-methoxyphenyl]-butanamide;

N-[4-(4-叔-丁基-苄基氨基)-2-甲氧基苯基]-丁酰胺；N-[4-(4-tert-butyl-benzylamino)-2-methoxyphenyl]-butanamide;

N-[2-甲氧基-4-(4-三氟甲基-苄基氨基)-苯基]-丁酰胺；N-[2-Methoxy-4-(4-trifluoromethyl-benzylamino)-phenyl]-butanamide;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-呋喃-2-基-苯基}-氨基甲酸丙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-furan-2-yl-phenyl}-carbamic acid propyl ester;

[2-呋喃-2-基-4-(4-异丙基苄基氨基)-苯基]-氨基甲酸丙酯；[2-furan-2-yl-4-(4-isopropylbenzylamino)-phenyl]-carbamic acid propyl ester;

[5-(4-氟苄基氨基)-联苯-2-基]-氨基甲酸丙酯；[5-(4-Fluorobenzylamino)-biphenyl-2-yl]-propyl carbamate;

{5-[(5-氯-噻吩-2-基甲基)-氨基]-联苯-2-基}-氨基甲酸丙酯；{5-[(5-Chloro-thiophen-2-ylmethyl)-amino]-biphenyl-2-yl}-propyl carbamate;

[5-(4-异丙基苄基氨基)-联苯-2-基]-氨基甲酸丙酯；[5-(4-Isopropylbenzylamino)-biphenyl-2-yl]-propyl carbamate;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-苯基乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-phenylacetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-3，3-二甲基丁酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3,3-dimethylbutanamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基)-3-苯基丙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl)-3-phenylpropanamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-丁酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-butanamide;

戊酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺；Valeric acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide;

环丙烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺；Cyclopropanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide;

环丁烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺；Cyclobutanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide;

环戊烷羧酸(2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺；Cyclopentanecarboxylic acid (2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide;

环己烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺；Cyclohexanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-噻吩-2-基-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-thiophen-2-yl-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(3-甲氧基-苯基]-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(3-methoxy-phenyl]-acetamide ;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(4-氯-苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-chloro-phenyl)-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(4-甲氧基-苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-methoxy-phenyl)-acetamide ;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(4-氟-苯基-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-fluoro-phenyl-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-3-环己基丙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-cyclohexylpropionamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2，2-二甲基丙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2,2-dimethylpropanamide;

N-[2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-苯氧基乙酰胺；N-[2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-phenoxyacetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-苯基乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-phenylacetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-3，3-二甲基丁酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-3,3-dimethylbutanamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-丁酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-butanamide;

戊酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺；Valeric acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide;

环丙烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺；Cyclopropanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide;

环丁烷羧酸(2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]＝苯基}-酰胺；Cyclobutanecarboxylic acid (2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]=phenyl}-amide;

环戊烷羧酸(2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺；Cyclopentanecarboxylic acid (2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide;

环己烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺；Cyclohexanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-噻吩-2-基-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-thiophen-2-yl-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-(3-甲氧基苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(3-methoxyphenyl)-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-(4-氯苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(4-chlorophenyl)-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-(4-甲氧基苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(4-methoxyphenyl)-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-(4-氟苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(4-fluorophenyl)-acetamide;

2，3-二氢-苯并[1，4]二噁烯-6-甲酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺；2,3-Dihydro-benzo[1,4]dioxene-6-carboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}- amides;

2，3-二氢-苯并呋喃-5-甲酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺；2,3-Dihydro-benzofuran-5-carboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-3-环己基丙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-3-cyclohexylpropionamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-2，2-二甲基丙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-2,2-dimethylpropanamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-2-苯基乙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-2-phenylacetamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-3，3-二甲基丁酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-3,3-dimethylbutanamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-3-苯基丙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-3-phenylpropanamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-丁酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-butanamide;

2，2，2-三氯-N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-乙酰胺；2,2,2-Trichloro-N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-acetamide;

环丙烷羧酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-酰胺；Cyclopropanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-amide;

环丁烷羧酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基J-酰胺；Cyclobutanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl J-amide;

环戊烷羧酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基、-酰胺；Cyclopentanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl,-amide;

环己烷羧酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基)-酰胺；Cyclohexanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl)-amide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-2-噻吩-2-基-乙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-thiophen-2-yl-acetamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}j-2-(3-甲氧基苯基)-乙酰胺；N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}j-2-(3-methoxyphenyl)-acetamide ;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-丙酰胺酸甲酯；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-propionamic acid methyl ester;

2-(4-氯苯基)-N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-乙酰胺；2-(4-chlorophenyl)-N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-acetamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-2-(4-甲氧基苯基)-乙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-(4-methoxyphenyl)-acetamide;

N-{4-[(5-氯-噻吩-2-基甲基)-甲基)氨基]-2-甲基苯基}-2-(4-氟苯基)-乙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-methyl)amino]-2-methylphenyl}-2-(4-fluorophenyl)-acetamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-3-环己基丙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-3-cyclohexylpropionamide;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸苯酯；{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-phenylcarbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸苄酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid benzyl ester;

(2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基)-氨基甲酸异丁酯；(2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl)-carbamic acid isobutyl ester;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丁酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸己酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-hexyl carbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸4-硝基苄酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 4-nitrobenzyl ester;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丁-3-烯酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-but-3-enylcarbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丁-2-炔酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-but-2-ynylcarbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸2，2-二甲基丙酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 2,2-dimethylpropyl ester;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基)-氨基甲酸2-氯苄酯；{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl)-carbamic acid 2-chlorobenzyl ester;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸3-氯丙酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-chloropropyl carbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸2-苄氧基乙酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 2-benzyloxyethyl ester;

3-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-1-甲基-1-丙基-脲；3-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-1-methyl-1-propyl-urea;

1-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-3-(2-氟苯基)-脲；1-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-(2-fluorophenyl)-urea;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2，2，2-三氟乙酰胺；和N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2,2,2-trifluoroacetamide; and

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2，2，2-三氟乙酰胺。N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2,2,2-trifluoroacetamide.

在另-个实施方案中，优选下面列出的化合物以及其盐：In another embodiment, the compounds listed below and their salts are preferred:

{4-[(苯并呋喃-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(Benzofuran-2-ylmethyl)-amino]-2-methylphenyl}-propyl carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamate ethyl ester;

(4-(苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸乙酯；(4-(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamate;

{2-甲基-4-[(5-苯基-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸乙酯；{2-Methyl-4-[(5-phenyl-thiophen-2-ylmethyl)-amino]-phenyl}-urethane;

[4-(4-异丙基-苄基氨基)-2-甲基苯基]-氨基甲酸乙酯；[4-(4-Isopropyl-benzylamino)-2-methylphenyl]-ethyl carbamate;

[4-(4-氟-苄基氨基)-2-甲基苯基]-氨基甲酸丙酯；[4-(4-Fluoro-benzylamino)-2-methylphenyl]-propyl carbamate;

(4-{[4-(4-氯-苯磺酰基)-3-甲基-噻吩-2-基甲基]-氨基}-2-甲基苯基)-氨基甲酸丙酯；(4-{[4-(4-Chloro-benzenesulfonyl)-3-methyl-thiophen-2-ylmethyl]-amino}-2-methylphenyl)-propyl carbamate;

{4-[(5-甲基-噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(5-Methyl-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-propyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-propyl carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-propyl carbamate;

{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-propyl carbamate;

{2-甲基-4-[(5-苯基-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{2-Methyl-4-[(5-phenyl-thiophen-2-ylmethyl)-amino]-phenyl}-propyl carbamate;

[4-(4-异丙基-苄基氨基)-2-甲基苯基]-氨基甲酸丙酯；[4-(4-Isopropyl-benzylamino)-2-methylphenyl]-propyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸乙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-ethyl carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-ethyl carbamate;

{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸乙酯；{4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-ethyl carbamate;

[2-氯-4-(4-异丙基-苄基氨基)-苯基]-氨基甲酸乙酯；[2-Chloro-4-(4-isopropyl-benzylamino)-phenyl]-carbamate ethyl ester;

[2-氯-4-(4-氟-苄基氨基)-苯基]-氨基甲酸丙酯；[2-Chloro-4-(4-fluoro-benzylamino)-phenyl]-carbamate propyl ester;

2-氯-4-{[4-(4-氯-苯磺酰基)-3-甲基-噻吩-2-基甲基]-氨基}-苯基)-氨基甲酸丙酯；2-Chloro-4-{[4-(4-chloro-benzenesulfonyl)-3-methyl-thiophen-2-ylmethyl]-amino}-phenyl)-propyl carbamate;

{4-[(5-甲基-噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸丙酯；{4-[(5-Methyl-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-propyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-propyl carbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-propyl carbamate;

{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸丙酯；{4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-propyl carbamate;

{4-[(苯并呋喃-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸乙酯；{4-[(benzofuran-2-ylmethyl)-amino]-2-chlorophenyl}-ethyl carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-氰基苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-cyanophenyl}-ethyl carbamate;

{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-甲氧基苯基}-氨基甲酸甲酯；{4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-methyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-甲氧基苯基}-氨基甲酸异丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-carbamate isopropyl ester;

{4-[(4-氟-苄基)-(甲基)氨基]-2-甲氧基苯基}-氨基甲酸丙酯；{4-[(4-Fluoro-benzyl)-(methyl)amino]-2-methoxyphenyl}-propyl carbamate;

[4-[(苯并[b]噻吩-2-基甲基-(甲基)氨基)-2-甲氧基苯基]-氨基甲酸丙酯；Propyl [4-[(benzo[b]thiophen-2-ylmethyl-(methyl)amino)-2-methoxyphenyl]-carbamate;

{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲氧基-苯基}-氨基甲酸丙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methoxy-phenyl}-carbamic acid propyl ester;

{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-甲氧基-苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-methoxy-phenyl}-propyl carbamate;

{2-甲氧基-4-[甲基-(5-甲基-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{2-Methoxy-4-[methyl-(5-methyl-thiophen-2-ylmethyl)-amino]-phenyl}-propyl carbamate;

{4-[(4-氟苄基)-(甲基)-氨基]-2-异丙氧基苯基}-氨基甲酸乙酯；{4-[(4-fluorobenzyl)-(methyl)-amino]-2-isopropoxyphenyl}-ethyl carbamate;

[4-(3-氟苄基氨基)-2-甲氧基苯基]-氨基甲酸乙酯；[4-(3-Fluorobenzylamino)-2-methoxyphenyl]-ethyl carbamate;

[4-(4-异丙基苄基氨基)-2-甲氧基苯基]-氨基甲酸乙酯；[4-(4-Isopropylbenzylamino)-2-methoxyphenyl]-ethyl carbamate;

{2-甲氧基-4-[(3-甲基噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸乙酯；{2-Methoxy-4-[(3-methylthiophen-2-ylmethyl)-amino]-phenyl}-urethane;

[4-(2，4-二氟苄基氨基)-2-甲氧基苯基]-氨基甲酸乙酯；[4-(2,4-Difluorobenzylamino)-2-methoxyphenyl]-ethyl carbamate;

[2-环戊氧基-4-(4-甲氧基苄基氨基)-苯基]-氨基甲酸乙酯；[2-Cyclopentyloxy-4-(4-methoxybenzylamino)-phenyl]-carbamate ethyl ester;

[2-环戊氧基-4-(3-氟-2-甲基苄基氨基)-苯基]-氨基甲酸乙酯；[2-Cyclopentyloxy-4-(3-fluoro-2-methylbenzylamino)-phenyl]-urethane;

[4-(3-氟-2-甲基苄基氨基)-2-苯乙氧基苯基]-氨基甲酸乙酯；[4-(3-Fluoro-2-methylbenzylamino)-2-phenethoxyphenyl]-ethyl carbamate;

[2-苄氧基-4-(3-氟-2-甲基苄基氨基)-苯基]-氨基甲酸乙酯；[2-Benzyloxy-4-(3-fluoro-2-methylbenzylamino)-phenyl]-carbamate ethyl ester;

[2-苄氧基-4-(4-甲基硫烷基苄基氨基)-苯基]-氨基甲酸乙酯；[2-Benzyloxy-4-(4-methylsulfanylbenzylamino)-phenyl]-ethyl carbamate;

[4-[(苯并[b]噻吩-3-基甲基)-氨基]-2-环戊氧基苯基]-氨基甲酸乙酯；[4-[(Benzo[b]thiophen-3-ylmethyl)-amino]-2-cyclopentyloxyphenyl]-urethane;

[4-(3-氟-2-甲基苄基氨基)-2-异丙氧基苯基]-氨基甲酸乙酯；[4-(3-Fluoro-2-methylbenzylamino)-2-isopropoxyphenyl]-ethyl carbamate;

[2-苄氧基-4-(3-甲基苄基氨基)-苯基]-氨基甲酸乙酯；[2-Benzyloxy-4-(3-methylbenzylamino)-phenyl]-ethyl carbamate;

[4-[(苯并[1，3]间二氧杂环戊烯-5-基甲基)-氨基]-2-异丙氧基苯基]-氨基甲酸乙酯；[4-[(Benzo[1,3]dioxol-5-ylmethyl)-amino]-2-isopropoxyphenyl]-urethane;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-phenyl}-carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-phenyl}-carbamate;

[2-氰基-4-(4-异丙氧基苄基氨基)-苯基]-氨基甲酸乙酯；[2-cyano-4-(4-isopropoxybenzylamino)-phenyl]-urethane;

{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-propyl carbamate;

{4-[(4-异丙基苄基)-(甲基)氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(4-isopropylbenzyl)-(methyl)amino]-2-methylphenyl}-propyl carbamate;

{2-甲基-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸丙酯；{2-Methyl-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-propyl carbamate;

{2-甲基-4-[甲基-(4-甲基硫烷基-苄基)-氨基]-苯基}-氨基甲酸丙酯；{2-Methyl-4-[methyl-(4-methylsulfanyl-benzyl)-amino]-phenyl}-propyl carbamate;

{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-氯苯基}-氨基甲酸乙酯；{4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-chlorophenyl}-ethyl carbamate;

{2-氯-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸乙酯；{2-Chloro-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-carbamate ethyl ester;

{2-氯-4-[甲基-(4-甲基硫烷基-苄基)-氨基]-苯基}-氨基甲酸乙酯；{2-Chloro-4-[methyl-(4-methylsulfanyl-benzyl)-amino]-phenyl}-ethyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-氯苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-chlorophenyl}-propyl carbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丙酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester;

{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-氯苯基}-氨基甲酸丙酯；{4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-chlorophenyl}-propyl carbamate;

{2-氯-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸丙酯；{2-Chloro-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-propyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamate ethyl ester;

{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamate ethyl ester;

{4-[(4-异丙基-苄基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[(4-Isopropyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-ethyl carbamate;

{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-ethyl carbamate;

{4-[甲基-(4-三氟甲基-苄基)-氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[Methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-ethyl carbamate;

{4-[甲基-(4-甲基硫烷基-苄基)-氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[Methyl-(4-methylsulfanyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-ethyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester;

{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester;

{4-[(4-异丙基-苄基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[(4-Isopropyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-propyl carbamate;

{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-propyl carbamate;

{4-[甲基-(4-三氟甲基-苄基)-氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[Methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-propyl carbamate;

{4-[甲基-(4-甲基硫烷基-苄基)-氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[Methyl-(4-methylsulfanyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-propyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-氰基苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-cyanophenyl}-propyl carbamate;

{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-氰基苯基}-氨基甲酸丙酯；{4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-cyanophenyl}-propyl carbamate;

{2-氰基-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸丙酯；{2-cyano-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-propyl carbamate;

{2-溴-4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丙酯；{2-bromo-4-[(5-bromo-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamate;

{2-溴-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丙酯；{2-Bromo-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester;

{2-溴-4-[(4-异丙基苄基)-(甲基)氨基]-苯基}-氨基甲酸丙酯；{2-Bromo-4-[(4-isopropylbenzyl)-(methyl)amino]-phenyl}-carbamate;

{2-溴-4-[(4-叔-丁基-苄基)-(甲基)氨基]-苯基}-氨基甲酸丙酯；{2-Bromo-4-[(4-tert-butyl-benzyl)-(methyl)amino]-phenyl}-propyl carbamate;

{2-溴-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸丙酯；{2-Bromo-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-propyl carbamate;

[2-碘-4-(4-异丙基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-iodo-4-(4-isopropyl-benzylamino)-phenyl]-carbamate;

[4-(4-叔-丁基-苄基氨基)-2-碘苯基]-氨基甲酸丙酯；[4-(4-tert-butyl-benzylamino)-2-iodophenyl]-propyl carbamate;

[2-碘-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-iodo-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamate propyl ester;

[2-碘-4-(4-甲基硫烷基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-iodo-4-(4-methylsulfanyl-benzylamino)-phenyl]-carbamate propyl ester;

{2-碘-4-[4-(4-甲基哌嗪-1-基)-苄基氨基]-苯基}-氨基甲酸丙酯；{2-iodo-4-[4-(4-methylpiperazin-1-yl)-benzylamino]-phenyl}-carbamic acid propyl ester;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl}-carbamate ethyl ester;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl}-carbamate ethyl ester;

[4-(4-叔-丁基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸乙酯；[4-(4-tert-butyl-benzylamino)-2-trifluoromethyl-phenyl]-ethyl carbamate;

[4-(4-甲基硫烷基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸乙酯；[4-(4-Methylsulfanyl-benzylamino)-2-trifluoromethyl-phenyl]-ethyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl}-propyl carbamate;

[4-(4-异丙基苄基氨基)-2-三氟甲基-苯基]-氨基甲酸丙酯；[4-(4-Isopropylbenzylamino)-2-trifluoromethyl-phenyl]-propyl carbamate;

[4-(4-叔-丁基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸丙酯；[4-(4-tert-butyl-benzylamino)-2-trifluoromethyl-phenyl]-propyl carbamate;

[2-三氟甲基-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-Trifluoromethyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid propyl ester;

[4-(4-二甲基氨基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸丙酯；[4-(4-Dimethylamino-benzylamino)-2-trifluoromethyl-phenyl]-propyl carbamate;

[4-(4-甲基硫烷基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸丙酯；[4-(4-Methylsulfanyl-benzylamino)-2-trifluoromethyl-phenyl]-propyl carbamate;

{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-氰基苯基}-氨基甲酸丙酯；{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-cyanophenyl}-propyl carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-氰基苯基}-氨基甲酸丙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-cyanophenyl}-propyl carbamate;

[2-氰基-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-cyano-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamate propyl ester;

{2-溴-4-[(5-溴-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{2-bromo-4-[(5-bromo-thiophen-2-ylmethyl)-amino]-phenyl}-propyl carbamate;

{2-溴-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯；{2-Bromo-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-propyl carbamate;

[2-溴-4-(4-异丙基苄基氨基)-苯基]-氨基甲酸丙酯；[2-Bromo-4-(4-isopropylbenzylamino)-phenyl]-carbamate;

[2-溴-4-(4-叔-丁基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-Bromo-4-(4-tert-butyl-benzylamino)-phenyl]-carbamate propyl ester;

[2-溴-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-Bromo-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid propyl ester;

[2-溴-4-(4-甲基硫烷基-苄基氨基)-苯基]-氨基甲酸丙酯；[2-Bromo-4-(4-methylsulfanyl-benzylamino)-phenyl]-carbamate propyl ester;

N-{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-甲氧基苯基}-丁酰胺；N-{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-butanamide;

N-{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-甲氧基苯基}-丁酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-butanamide;

N-[4-(4-异丙基苄基氨基)-2-甲氧基苯基]-丁酰胺；N-[4-(4-isopropylbenzylamino)-2-methoxyphenyl]-butanamide;

N-[4-(4-叔-丁基-苄基氨基)-2-甲氧基苯基]-丁酰胺；N-[4-(4-tert-butyl-benzylamino)-2-methoxyphenyl]-butanamide;

N-[2-甲氧基-4-(4-三氟甲基-苄基氨基)-苯基]-丁酰胺；N-[2-Methoxy-4-(4-trifluoromethyl-benzylamino)-phenyl]-butanamide;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-呋喃-2-基-苯基}-氨基甲酸丙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-furan-2-yl-phenyl}-carbamic acid propyl ester;

[2-呋喃-2-基-4-(4-异丙基苄基氨基)-苯基]-氨基甲酸丙酯；[2-furan-2-yl-4-(4-isopropylbenzylamino)-phenyl]-carbamic acid propyl ester;

[5-(4-氟苄基氨基)-联苯-2-基]-氨基甲酸丙酯；[5-(4-Fluorobenzylamino)-biphenyl-2-yl]-propyl carbamate;

{5-[(5-氯-噻吩-2-基甲基)-氨基]-联苯-2-基}-氨基甲酸丙酯；{5-[(5-Chloro-thiophen-2-ylmethyl)-amino]-biphenyl-2-yl}-propyl carbamate;

[5-(4-异丙基苄基氨基)-联苯-2-基]-氨基甲酸丙酯；[5-(4-Isopropylbenzylamino)-biphenyl-2-yl]-propyl carbamate;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-苯基乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-phenylacetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-3，3-二甲基丁酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3,3-dimethylbutanamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-3-苯基丙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-phenylpropanamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-丁酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-butanamide;

戊酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺；Valeric acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide;

环丙烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺；Cyclopropanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide;

环丁烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺；Cyclobutanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide;

环戊烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺；Cyclopentanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide;

环己烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基-苯基}-酰胺；Cyclohexanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino-phenyl}-amide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-噻吩-2-基-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-thiophen-2-yl-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(3-甲氧基-苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(3-methoxy-phenyl)-acetamide ;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(4-氯-苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-chloro-phenyl)-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(4-甲氧基-苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-methoxy-phenyl)-acetamide ;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(4-氟-苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-fluoro-phenyl)-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-3-环己基丙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-cyclohexylpropionamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2，2-二甲基丙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2,2-dimethylpropanamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-苯氧基乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-phenoxyacetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2--苯基乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2--phenylacetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-3，3-二甲基丁酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-3,3-dimethylbutanamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-丁酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-butanamide;

戊酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺；Valeric acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide;

环丙烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺；Cyclopropanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide;

环丙烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺；Cyclopropanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide;

环戊烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基)-酰胺；Cyclopentanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl)-amide;

环己烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺；Cyclohexanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-噻吩-2-基-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-thiophen-2-yl-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-(3-甲氧基苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(3-methoxyphenyl)-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-(4-氯苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(4-chlorophenyl)-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-(4-甲氧基苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(4-methoxyphenyl)-acetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-(4-氟苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(4-fluorophenyl)-acetamide;

2，3-二氢-苯并[1，4]二噁烯-6-甲酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺；2,3-Dihydro-benzo[1,4]dioxene-6-carboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}- amides;

2，3-二氢-苯并呋喃-5-甲酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]苯基}-酰胺；2,3-Dihydro-benzofuran-5-carboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]phenyl}-amide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-3-环己基丙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-3-cyclohexylpropionamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-2，2-二甲基丙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-2,2-dimethylpropanamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-2-苯基乙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-2-phenylacetamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-3，3-二甲基丁酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-3,3-dimethylbutanamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-3-苯基丙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-3-phenylpropanamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-丁酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-butanamide;

2，2，2-三氯-N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-乙酰胺；2,2,2-Trichloro-N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-acetamide;

环丙烷羧酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-酰胺；Cyclopropanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-amide;

环丁烷羧酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-酰胺；Cyclobutanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-amide;

环戊烷羧酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-酰胺；Cyclopentanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-amide;

环己烷羧酸[4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基)-酰胺；Cyclohexanecarboxylic acid [4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl)-amide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-2-噻吩-2-基-乙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-thiophen-2-yl-acetamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-2-(3-甲氧基苯基)-乙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-(3-methoxyphenyl)-acetamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-丙酰胺酸甲酯；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-propionamic acid methyl ester;

2-(4-氯苯基)-N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-乙酰胺；2-(4-chlorophenyl)-N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-acetamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-2-(4-甲氧基苯基)-乙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-(4-methoxyphenyl)-acetamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-2-(4-氟苯基)-乙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-(4-fluorophenyl)-acetamide;

N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-3-环己基丙酰胺；N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-3-cyclohexylpropionamide;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸苯酯；{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-phenylcarbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸苄酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid benzyl ester;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸异丁酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid isobutyl ester;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丁酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸己酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-hexyl carbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸4-硝基苄酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 4-nitrobenzyl ester;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丁-3-烯酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-but-3-enylcarbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丁-2-炔基酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid but-2-ynyl ester;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸2，2-二甲基丙酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 2,2-dimethylpropyl ester;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸2-氯苄酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 2-chlorobenzyl ester;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸3-氯丙酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-chloropropyl carbamate;

{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸2-苄氧基乙酯；{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 2-benzyloxyethyl ester;

3-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-1-甲基-1-丙基-脲；3-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-1-methyl-1-propyl-urea;

1-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-3-(2-氟苯基)-脲；1-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-(2-fluorophenyl)-urea;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2，2，2-三氟乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2,2,2-trifluoroacetamide;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2，2，2-三氟乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2,2,2-trifluoroacetamide;

N-{5-[(5-氯-噻吩-2-基甲基)-氨基]-4′-二甲基氨基-联苯-2-基}-2-(4-氟苯基)-乙酰胺；N-{5-[(5-chloro-thiophen-2-ylmethyl)-amino]-4'-dimethylamino-biphenyl-2-yl}-2-(4-fluorophenyl)-ethyl amides;

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基氨基]-苯基}-2-(4-氯苯基)-乙酰胺；N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methylamino]-phenyl}-2-(4-chlorophenyl)-acetamide;

[4-(3-氟-4-三氟甲基-苄基氨基)-2-甲基苯基]-氨基甲酸乙酯；[4-(3-Fluoro-4-trifluoromethyl-benzylamino)-2-methylphenyl]-ethyl carbamate;

2-(4-氟苯基)-N-{2-甲基-4-[(6-对-甲苯氧基吡啶-3-基甲基)-氨基]-苯基}-乙酰胺；2-(4-fluorophenyl)-N-{2-methyl-4-[(6-p-tolyloxypyridin-3-ylmethyl)-amino]-phenyl}-acetamide;

N-{2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-丁酰胺；N-{2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-butanamide;

2-(4-氟苯基)-N-{2-甲基-4-[(6-三氟甲基吡啶-3-基甲基)-氨基]-苯基}-乙酰胺；2-(4-fluorophenyl)-N-{2-methyl-4-[(6-trifluoromethylpyridin-3-ylmethyl)-amino]-phenyl}-acetamide;

戊酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-酰胺；Valeric acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-amide;

3，3-二甲基-N-{2-甲基-4-[(6-对-甲苯氧基吡啶-3-基甲基)-氨基]-苯基}-丁酰胺；3,3-Dimethyl-N-{2-methyl-4-[(6-p-tolyloxypyridin-3-ylmethyl)-amino]-phenyl}-butanamide;

[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸乙酯；[2-Methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamate ethyl ester;

N-(2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(4-氯苯基)-丙酰胺；N-(2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-chlorophenyl)-propionamide;

[4-(4-氯-苄基氨基)-2-甲基苯基]-氨基甲酸乙酯；[4-(4-Chloro-benzylamino)-2-methylphenyl]-ethyl carbamate;

{4-[(6-甲氧基-苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(6-Methoxy-benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-propyl carbamate;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-喹啉-3-基-苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-quinolin-3-yl-phenyl}-carbamic acid ethyl ester;

{4-[(5-二甲基氨基-3-甲基-苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}2-氨基甲酸丙酯；{4-[(5-Dimethylamino-3-methyl-benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}2-propyl carbamate;

3，3-二甲基-N-{2-甲基-4-[(6-三氟甲基吡啶-3-基甲基)-氨基]-苯基}-丁酰胺；3,3-Dimethyl-N-{2-methyl-4-[(6-trifluoromethylpyridin-3-ylmethyl)-amino]-phenyl}-butanamide;

N-(4-{[6-氯-(4-氰基苯氧基)-吡啶-3-基甲基]-氨基}-2-甲基苯基)-2-(4-氯苯基)-乙酰胺；N-(4-{[6-chloro-(4-cyanophenoxy)-pyridin-3-ylmethyl]-amino}-2-methylphenyl)-2-(4-chlorophenyl) - acetamide;

{2-苄氧基-4-[(4-氟苄基)-(甲基)氨基]-苯基}-硫代氨基甲酸S-乙酯；{2-Benzyloxy-4-[(4-fluorobenzyl)-(methyl)amino]-phenyl}-thiocarbamic acid S-ethyl ester;

{2-环烷氧基-4-[(4-氟苄基)-(甲基)氨基]-苯基}-硫代氨基甲酸S-乙酯；{2-Cycloalkoxy-4-[(4-fluorobenzyl)-(methyl)amino]-phenyl}-thiocarbamic acid S-ethyl ester;

N-{4-[(6-氯吡啶-3-基甲基)-氨基]-2-甲基苯基}-2-(4-氯苯基)-乙酰胺；N-{4-[(6-chloropyridin-3-ylmethyl)-amino]-2-methylphenyl}-2-(4-chlorophenyl)-acetamide;

{4-[(7-二甲基氨基-苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯；{4-[(7-Dimethylamino-benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-propyl carbamate;

1-{2-环戊氧基-4-[(4-氟苄基)-(甲基)氨基]-苯基}-3-乙基-脲；1-{2-cyclopentyloxy-4-[(4-fluorobenzyl)-(methyl)amino]-phenyl}-3-ethyl-urea;

2-氨基-4-甲基-戊酸[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-酰胺；2-Amino-4-methyl-pentanoic acid [2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-amide;

{4-[(6-甲氧基-苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸乙酯；{4-[(6-Methoxy-benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-ethyl carbamate;

2-氨基-4-甲基-戊酸[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基-酰胺；2-Amino-4-methyl-pentanoic acid [2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl-amide;

2-(4-氟苯基)-N-{2-甲基-4-[(4-甲基-2-苯基嘧啶-5-基甲基)-氨基]-苯基}-乙酰胺；2-(4-fluorophenyl)-N-{2-methyl-4-[(4-methyl-2-phenylpyrimidin-5-ylmethyl)-amino]-phenyl}-acetamide;

3，3-二甲基-N-{2-甲基-4-[(2-苯基嘧啶-5-基甲基)-氨基]-苯基}-丁酰胺；3,3-Dimethyl-N-{2-methyl-4-[(2-phenylpyrimidin-5-ylmethyl)-amino]-phenyl}-butanamide;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-吡啶-3-基-苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-pyridin-3-yl-phenyl}-carbamic acid ethyl ester;

1-氨基-环丙烷羧酸[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基-酰胺；1-Amino-cyclopropanecarboxylic acid [2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl-amide;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-吡啶-4-基-苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-pyridin-4-yl-phenyl}-carbamic acid ethyl ester;

N-[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-2-哌啶-1-基-乙酰胺；N-[2-Methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-piperidin-1-yl-acetamide;

N-(4-{[5-(4-氯苯氧基)-1，3-二甲基-1H-吡唑-4-基甲基]-氨基}-2-甲基苯基)-2，2-二甲基丙酰胺；N-(4-{[5-(4-chlorophenoxy)-1,3-dimethyl-1H-pyrazol-4-ylmethyl]-amino}-2-methylphenyl)-2 , 2-dimethylpropanamide;

2，2-二甲基-N-{2-甲基-4-[(6-苯氧基吡啶-3-基甲基)-氨基]-苯基}-丙酰胺；2,2-Dimethyl-N-{2-methyl-4-[(6-phenoxypyridin-3-ylmethyl)-amino]-phenyl}-propionamide;

N-[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-2-吡咯烷-1-基-乙酰胺；N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-pyrrolidin-1-yl-acetamide;

[4-[(5-氯-噻吩-2-基甲基)-氨基]-2-(6-甲氧基吡啶-3-基)-苯基]-氨基甲酸乙酯；[4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-(6-methoxypyridin-3-yl)-phenyl]-urethane;

4-[(3-甲基-4-丙氧基羰基氨基-苯基氨基)-甲基]-苯甲酸甲酯；4-[(3-Methyl-4-propoxycarbonylamino-phenylamino)-methyl]-benzoic acid methyl ester;

N-[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-2-吗啉-4-基-乙酰胺；N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-morpholin-4-yl-acetamide;

2，2-二甲基-N-{2-甲基-4-[(3-甲基-5-苯基异噁唑-4-基甲基)-氨基]-苯基}-丙酰胺；2,2-Dimethyl-N-{2-methyl-4-[(3-methyl-5-phenylisoxazol-4-ylmethyl)-amino]-phenyl}-propionamide;

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-碘苯基}-氨基甲酸乙酯；{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-iodophenyl}-ethyl carbamate;

N-{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-碘苯基}-2-(4-氟苯基)-乙酰胺；和N-{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-iodophenyl}-2-(4-fluorophenyl)-acetamide; and

{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-喹啉-5-基-苯基}-氨基甲酸乙酯。{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-quinolin-5-yl-phenyl}-urethane ethyl ester.

根据一个实施方案，本发明涉及一种包含一种或多种可药用载体或稀释剂和其中s、q、U、X、Z、Y、R1、R2和R3的定义如上所述，a、b、c、d、e、f、g、h、s、q、U、X、Z、Y、W、R1、R2、R3、R5、R6、R6′、R7、R7′、R8、R9、R9′、R10、R10′、R11、R12和R12′中的任何一项相应地具有式I下所定义的含义的式I的化合物或其盐的药物组合物。因此，本发明的药物组合物可包含一种或多种式I的化合物或其盐，如一种式I的化合物或其盐；或两种式I的化合物或其盐；或三种式I的化合物或其盐。According to one embodiment, the present invention relates to a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers or diluents and wherein s, q, U, X, Z, Y, R 1 , R 2 and R 3 are as defined above , a, b, c, d, e, f, g, h, s, q, U, X, Z, Y, W, R 1 , R 2 , R 3 , R 5 , R 6 , R 6′ , Any one of R 7 , R 7′ , R 8 , R 9 , R 9′ , R 10 , R 10′ , R 11 , R 12 and R 12′ correspondingly has the formula defined under formula I A pharmaceutical composition of the compound of I or a salt thereof. Therefore, the pharmaceutical composition of the present invention may comprise one or more compounds of formula I or salts thereof, such as one compound of formula I or salts thereof; or two compounds of formula I or salts thereof; or three compounds of formula I compound or its salt.

根据一个实施方案，本发明涉及包含一种或多种可药用的载体或稀释剂和其中f、s、q、U、X、Z、R1、R2、R3和R5的定义如上所述，f、s、q、U、X、Z、R1、R2、R3、R5、R6、R6′、R7、R7′、R8、R9、R9′、R10、R10′、R11、R12和R12′中的任何一项相应地具有式XXIX下所定义的含义的式XXIX的化合物的药物组合物。因此，本发明的药物组合物可包含一种或多种式XXIX的化合物或其盐，如一种式XXIX的化合物或其盐；或两种式XXIX的化合物或其盐；或三种式XXIX的化合物或其盐。According to one embodiment, the present invention relates to comprising one or more pharmaceutically acceptable carriers or diluents and wherein f, s, q, U, X, Z, R 1 , R 2 , R 3 and R 5 are as defined above Said, f, s, q, U, X, Z, R 1 , R 2 , R 3 , R 5 , R 6 , R 6′ , R 7 , R 7 ′ , R 8 , R 9 , R 9 ′ Any one of R 10 , R 10' , R 11 , R 12 and R 12' correspondingly has the pharmaceutical composition of the compound of formula XXIX defined under formula XXIX. Therefore, the pharmaceutical composition of the present invention may comprise one or more compounds of formula XXIX or salts thereof, such as one compound of formula XXIX or salts thereof; or two compounds of formula XXIX or salts thereof; or three compounds of formula XXIX compound or its salt.

根据一个实施方案，本发明涉及一种包含一种或多种可药用的载体或稀释剂和其中g、h、s、q、U、X、Z、R1、R2、R3和R5的定义如上所述，g、h、s、q、U、X、Z、R1、R2、R3、R5、R6、R6′、R7、R7′、R8、R9、R9′、R10、R10′、R11、R12和R12′中的任何一项相应地具有式XXX下所定义的含义的式XXX的化合物的药物组合物。因此，本发明的药物组合物可包含一种或多种式XXX的化合物或其盐，如一种式XXX的化合物或其盐；或两种式XXX的化合物或其盐；或三种式XXX的化合物或其盐。According to one embodiment, the present invention relates to a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers or diluents and wherein g, h, s, q, U, X, Z, R 1 , R 2 , R 3 and R 5 is defined as above, g, h, s, q, U, X, Z, R 1 , R 2 , R 3 , R 5 , R 6 , R 6′ , R 7 , R 7′ , R 8 , Any one of R 9 , R 9' , R 10 , R 10' , R 11 , R 12 and R 12' correspondingly has a pharmaceutical composition of the compound of formula XXX as defined under formula XXX. Therefore, the pharmaceutical composition of the present invention may comprise one or more compounds of formula XXX or salts thereof, such as one compound of formula XXX or salts thereof; or two compounds of formula XXX or salts thereof; or three compounds of formula XXX compound or its salt.

根据一个实施方案，本发明涉及一种包含一种或多种可药用的载体或稀释剂和其中a、s、q、U、W、X、Z、R1、R2、R3和R5的定义如上所述，a、s、q、U、W、X、Z、R1、R2、R3、R5、R6、R6′、R7、R7′、R8、R9、R9′、R10、R10′、R11、R12和R12′中的任何一项相应地具有式XXXI下所定义的含义的式XXXI的化合物的药物组合物。因此，本发明的药物组合物可包含一种或多种式XXXI的化合物或其盐，如一种式XXXI的化合物或其盐；或两种式XXXI的化合物或其盐；或三种式XXXI的化合物或其盐。According to one embodiment, the present invention relates to a drug comprising one or more pharmaceutically acceptable carriers or diluents and wherein a, s, q, U, W, X, Z, R 1 , R 2 , R 3 and R 5 is defined as above, a, s, q, U, W, X, Z, R 1 , R 2 , R 3 , R 5 , R 6 , R 6′ , R 7 , R 7′ , R 8 , Any one of R 9 , R 9' , R 10 , R 10' , R 11 , R 12 and R 12' correspondingly has the pharmaceutical composition of the compound of formula XXXI as defined under formula XXXI. Therefore, the pharmaceutical composition of the present invention may comprise one or more compounds of formula XXXI or salts thereof, such as one compound of formula XXXI or salts thereof; or two compounds of formula XXXI or salts thereof; or three compounds of formula XXXI compound or its salt.

根据一个实施方案，本发明涉及一种包含一种或多种可药用的载体或稀释剂和其中b、c、s、q、U、W、X、Z、R1、R2、R3和R5的定义如上所述，b、c、s、q、U、W、X、Z、R1、R2、R3、R5、R6、R6′、R7、R7′、R8、R9、R9′、R10、R10′、R11、R12和R12′中的任何一项相应地具有式XXXII下所定义的含义的式XXXII的药物组合物。因此，本发明的药物组合物可包含一种或多种式XXXII的化合物或其盐，如一种式XXXII的化合物或其盐；或两种式XXXII的化合物或其盐；或三种式XXXII的化合物或其盐。According to one embodiment, the present invention relates to a method comprising one or more pharmaceutically acceptable carriers or diluents and wherein b, c, s, q, U, W, X, Z, R 1 , R 2 , R 3 and R 5 are as defined above, b, c, s, q, U, W, X, Z, R 1 , R 2 , R 3 , R 5 , R 6 , R 6′ , R 7 , R 7′ Any one of , R 8 , R 9 , R 9' , R 10 , R 10' , R 11 , R 12 and R 12' correspondingly has the pharmaceutical composition of formula XXXII as defined under formula XXXII. Therefore, the pharmaceutical composition of the present invention may comprise one or more compounds of formula XXXII or salts thereof, such as one compound of formula XXXII or salts thereof; or two compounds of formula XXXII or salts thereof; or three compounds of formula XXXII compound or its salt.

根据一个实施方案，本发明涉及一种包含一种或多种可药用的载体或稀释剂和其中d、e、s、q、U、W、X、Z、R1、R2、R3和R5的定义如上所述，d、e、s、q、U、W、X、Z、R1、R2、R3、R5、R6、R6、R7、R7、R8、R9、R9′、R10、R10′、R11、R12和R12′中的任何一项相应地具有式XXXIII下所定义的含义的式XXXIII的化合物的药物组合物。因此，本发明的药物组合物可包含一种或多种式XXXIII的化合物或其盐，如一种式XXXIII的化合物或其盐；或两种式XXXIII的化合物或其盐；或三种式XXXIII的化合物或其盐。According to one embodiment, the present invention relates to a drug comprising one or more pharmaceutically acceptable carriers or diluents and wherein d, e, s, q, U, W, X, Z, R 1 , R 2 , R 3 and R 5 are as defined above, d, e, s, q, U, W, X, Z, R 1 , R 2 , R 3 , R 5 , R 6 , R 6 , R 7 , R 7 , R Any one of 8 , R 9 , R 9′ , R 10 , R 10′ , R 11 , R 12 and R 12′ correspondingly has the pharmaceutical composition of the compound of formula XXXIII having the meaning defined under formula XXXIII. Therefore, the pharmaceutical composition of the present invention may comprise one or more compounds of formula XXXIII or salts thereof, such as one compound of formula XXXIII or salts thereof; or two compounds of formula XXXIII or salts thereof; or three compounds of formula XXXIII compound or its salt.

因此，本发明提供了一种用于口服或胃肠外给药的药物组合物，所说的药物组合物包含治疗有效量的至少一种式I或XXIX或XXX或XXXI或XXXII或XXXIII的化合物或其盐和一种或多种可药用的载体或稀释剂。Accordingly, the present invention provides a pharmaceutical composition for oral or parenteral administration, said pharmaceutical composition comprising a therapeutically effective amount of at least one compound of formula I or XXIX or XXX or XXXI or XXXII or XXXIII or a salt thereof and one or more pharmaceutically acceptable carriers or diluents.

在一个方面，本发明的化合物可以以唯一治疗有效化合物的形式被给药。In one aspect, the compounds of the invention may be administered as the only therapeutically effective compound.

在另一个方面，本发明的化合物可以以联合疗法一部分的形式被给药，即本发明的化合物可以与具有例如抗-惊厥性的其它治疗有效的化合物联合给药。该类具有抗-惊厥性的其它化合物的作用可非限制性地包括对下面方面的作用：In another aspect, the compounds of the invention may be administered as part of a combination therapy, ie the compounds of the invention may be administered in combination with other therapeutically effective compounds having, for example, anti-convulsant properties. The effects of this class of other compounds having anti-convulsant properties may include, but are not limited to, effects on:

●离子通道如钠、钾、或钙通道●Ion channels such as sodium, potassium, or calcium channels

○兴奋性氨基酸系统例如阻断或调控NMDA受体○ Excitatory amino acid systems such as blocking or modulating NMDA receptors

●抑制性神经递质系统例如增强GABA释放，或阻断GABA-吸收或Inhibitory neurotransmitter systems such as enhancing GABA release, or blocking GABA-absorption or

○膜稳定作用。○ Membrane stabilization.

目前的抗-惊厥药非限制性地包括硫加宾、卡马西平、丙戊酸钠、拉莫三嗪、加巴喷丁、普加巴林、乙琥胺、左乙拉西坦、苯妥英、托吡酯、唑尼沙胺以及苯并二氮杂_和巴比妥酸盐类的成员。Current anti-convulsants include, but are not limited to, tiagabine, carbamazepine, sodium valproate, lamotrigine, gabapentin, pregabalin, ethosuximide, levetiracetam, phenytoin, topiramate, azone Salamines and members of the benzodiazepine and barbiturate classes.

在一个方面，已经发现本发明的化合物对KCNQ族的钾通道，特别是KCNQ2子单元的钾通道有作用。In one aspect, the compounds of the invention have been found to have an effect on potassium channels of the KCNQ family, particularly potassium channels of the KCNQ2 subunit.

在一个实施方案中，本发明涉及一种或多种本发明的化合物在治疗方法中的应用。所预防、治疗或抑制的病症或情况是对钾通道KCNQ族钾离子通道的离子流量增加有响应的病症或情况。该类病症或情况优选地是中枢神经系统的病症或情况。In one embodiment, the invention relates to the use of one or more compounds of the invention in a method of therapy. The disorder or condition to be prevented, treated or inhibited is a disorder or condition that is responsive to an increase in ion flux of potassium ion channels of the KCNQ family of potassium channels. Such disorders or conditions are preferably disorders or conditions of the central nervous system.

认为本发明的化合物可用于增加哺乳动物如人电压依赖性钾通道中的离子流量。The compounds of the invention are believed to be useful for increasing ion flux in voltage-dependent potassium channels in mammals, such as humans.

认为本发明的化合物可用于预防、治疗或抑制对钾通道如KCNQ族钾离子通道的离子流量增加有响应的病症或情况。该类病症或情况优选地是中枢神经系统的病症或情况。The compounds of the present invention are believed to be useful in the prevention, treatment or inhibition of disorders or conditions responsive to increased ion flux of potassium channels, such as the KCNQ family of potassium ion channels. Such disorders or conditions are preferably disorders or conditions of the central nervous system.

因此，认为本发明的化合物可用于预防、治疗或抑制诸如如癫痫发作病症、神经性疼痛和偏头痛性头痛病症、焦虑障碍和神经变性病症之类的病症或疾病。Accordingly, the compounds of the present invention are considered useful for preventing, treating or inhibiting conditions or diseases such as, for example, epileptic seizure disorders, neuropathic pain and migraine headache disorders, anxiety disorders and neurodegenerative disorders.

因此，认为本发明的化合物可用于预防、治疗或抑制诸如惊厥、癫痫、焦虑障碍、神经性疼痛和神经变性病症之类的病症或情况。Accordingly, the compounds of the present invention are believed to be useful in the prevention, treatment or suppression of disorders or conditions such as convulsions, epilepsy, anxiety disorders, neuropathic pain and neurodegenerative disorders.

因此，根据一个特定的实施方案，认为本发明的化合物可用于预防、治疗或抑制癫痫发作病症如惊厥、癫痫和癫痫持续状态。Thus, according to a particular embodiment, the compounds of the present invention are considered useful for preventing, treating or inhibiting epileptic seizure disorders such as convulsions, epilepsy and status epilepticus.

在一个实施方案中，认为本发明的化合物可用于预防、治疗和抑制惊厥。In one embodiment, the compounds of the present invention are believed to be useful in the prevention, treatment and inhibition of convulsions.

在另一个实施方案中，认为本发明的化合物可用于预防、治疗和抑制癫痫、痫症和癫痫性发作。In another embodiment, the compounds of the present invention are believed to be useful in the prevention, treatment and suppression of epilepsy, epilepsy and epileptic seizures.

在另一个实施方案中，认为本发明的化合物可用于预防、治疗和抑制焦虑障碍如焦虑和与恐慌发作有关的情况和疾病、广场恐怖症、与广场恐怖症有关的恐慌病症、与广场恐怖症无关的恐慌病症、无恐慌病症史的广场恐怖症、特异恐怖、社交恐怖症和其它特异恐怖、强迫症、创伤后应激障碍、急性应激障碍、泛化性焦虑症、由于一般性医学情况造成的焦虑障碍、物质诱导的焦虑障碍、离别焦虑障碍、适应性障碍、行为性焦虑、疑病障碍、由于一般性医学情况造成的焦虑障碍和物质诱导的焦虑障碍和未特定指明的焦虑障碍。In another embodiment, the compounds of the present invention are believed to be useful in the prevention, treatment and suppression of anxiety disorders such as anxiety and conditions and disorders associated with panic attacks, agoraphobia, panic disorders associated with agoraphobia, agoraphobia Unrelated panic disorder, agoraphobia without history of panic disorder, specific phobias, social and other specific phobias, obsessive-compulsive disorder, post-traumatic stress disorder, acute stress disorder, generalized anxiety disorder, due to general medical condition Caused anxiety disorder, substance-induced anxiety disorder, separation anxiety disorder, adjustment disorder, behavioral anxiety, hypochondriac disorder, anxiety disorder due to a general medical condition and substance-induced anxiety disorder, and anxiety disorder unspecified.

在另一个实施方案中，认为本发明的化合物可用于预防、治疗和抑制神经性疼痛和偏头痛性疼痛病症如异常性疼痛、痛觉过敏性疼痛、幻痛、与糖尿病性神经病有关的神经性疼痛和与偏头痛有关的神经性(neupathic)疼痛。In another embodiment, the compounds of the present invention are believed to be useful in the prevention, treatment and inhibition of neuropathic pain and migrainous pain conditions such as allodynia, hyperalgesic pain, phantom pain, neuropathic pain associated with diabetic neuropathy and neupathic pain associated with migraine.

在另一个实施方案中，认为本发明的化合物可用于预防、治疗和抑制神经变性病症如阿耳茨海默氏病；亨廷顿舞蹈病；多发性硬化；肌萎缩性侧索硬化；Creutzfeld-Jakob病；帕金森氏病；AIDS或风疹病毒、疱疹病毒、包柔氏螺旋体属和未知病原体感染诱导的脑病；创伤诱导的神经变性；神经元兴奋过度状态如药物戒断或中毒中的状态；和外周神经系统的神经变性疾病如多神经病和多神经炎(polyneuritides)。In another embodiment, the compounds of the present invention are considered useful in the prevention, treatment and inhibition of neurodegenerative disorders such as Alzheimer's disease; Huntington's disease; multiple sclerosis; amyotrophic lateral sclerosis; Creutzfeld-Jakob disease ; Parkinson's disease; AIDS or encephalopathy induced by infection with rubella virus, herpes virus, Borrelia, and unknown pathogens; trauma-induced neurodegeneration; neuronal hyperexcitability states such as those in drug withdrawal or intoxication; and peripheral Neurodegenerative diseases of the nervous system such as polyneuropathy and polyneuritis (polyneuritis).

在另一个实施方案中，认为本发明的化合物可用于预防、治疗和抑制神经变性病症如阿耳茨海默氏病；亨廷顿舞蹈病；多发性硬化；肌萎缩性侧索硬化；Creutzfeld-Jakob病；帕金森氏病；AIDS或风疹病毒、疱疹病毒、包柔氏螺旋体属和未知的病原体感染诱导的脑病；和创伤诱导的神经变性。In another embodiment, the compounds of the present invention are considered useful in the prevention, treatment and inhibition of neurodegenerative disorders such as Alzheimer's disease; Huntington's disease; multiple sclerosis; amyotrophic lateral sclerosis; Creutzfeld-Jakob disease ; Parkinson's disease; AIDS or infection-induced encephalopathy with rubella virus, herpes virus, borrelia, and unknown pathogens; and trauma-induced neurodegeneration.

在另一个实施方案中，认为本发明的化合物可用于预防、治疗和抑制神经元兴奋过度状态如药物戒断或中毒中的状态。In another embodiment, the compounds of the present invention are believed to be useful in the prevention, treatment and inhibition of neuronal hyperexcitatory states such as those in drug withdrawal or intoxication.

本发明提供了在一种或多种下面的试验中表现出作用的化合物：The present invention provides compounds that exhibit action in one or more of the following assays:

●“通过KCNQ2通道的相对外向流量”● "Relative outward flux through the KCNQ2 channel"

其是化合物对目标通道功效的度量It is a measure of the potency of the compound on the target channel

●“最大电休克”● "Maximum Electric Shock"

其是通过电方法通过非特异性CNS刺激诱导的癫痫发作的度量It is a measure of seizures induced by non-specific CNS stimulation by electrical means

●“毛果芸香碱诱导的癫痫发作”● "Pilocarpine-induced seizures"

毛果芸香碱诱导的癫痫发作常常难以用许多现存的抗癫痫发作药来进行治疗并且从而反应了一种“耐药的癫痫发作”模型Pilocarpine-induced seizures are often refractory to many existing antiseizure drugs and thus reflect a "drug-resistant seizure" model

●“电癫痫发作-阈值试验”和“化学癫痫发作-阈值试验”● "Electrical Seizure-Threshold Test" and "Chemical Seizure-Threshold Test"

这些模型测量了在其下开始癫痫发作的阈值，因此，其是探测这些化合物是否会延迟癫痫发作开始的模型。These models measure the threshold below which seizures start and are therefore models for probing whether these compounds delay seizure onset.

○“扁桃体兴奋”○ "tonsillar excitement"

用其作为疾病进展的度量，与正常动物相比，当动物接受进一步刺激时，这种模型中的癫痫发作更严重。Using this as a measure of disease progression, seizures were more severe in this model when the animals received further stimulation compared with normal animals.

根据本发明的一个特定方面，该化合物具有KCNQ2活性，在用下面所述的“通过KCNQ2通道的相对外向流量”试验进行测量时，其具有小于15000nM如小于10000nM的EC50。According to a particular aspect of the invention, the compound has KCNQ2 activity having an EC50 of less than 15000 nM, such as less than 10000 nM, as measured by the "Relative Outward Flux Through KCNQ2 Channels" assay described below.

根据本发明的一个特定方面，该化合物具有KCNQ2活性，在用下面所述的“通过KCNQ2通道的相对外向流量”试验进行测量时，其具有小于2000nM如小于1500nM的EC50。According to a particular aspect of the invention, the compound has KCNQ2 activity having an EC50 of less than 2000 nM, such as less than 1500 nM, as measured by the "Relative Outward Flux Through KCNQ2 Channels" assay described below.

根据本发明的另一个特定方面，该化合物具有KCNQ2活性，在用下面所述的“通过KCNQ2通道的相对外向流量”试验进行测量时，其具有小于200nM如小于150nM的EC50。According to another particular aspect of the invention, the compound has KCNQ2 activity having an EC50 of less than 200 nM, such as less than 150 nM, as measured by the "Relative Outward Flux Through KCNQ2 Channels" assay described below.

根据本发明的另一个特定方面，这些化合物在下面所述的“最大电休克”试验中具有小于15mg/kg的ED50。According to another particular aspect of the invention, these compounds have an ED50 of less than 15 mg/kg in the "maximal electroshock" test described below.

根据本发明的另一个特定方案，这些化合物在下面所述的“最大电休克”试验中具有小于5mg/kg的ED50。According to another particular aspect of the invention, these compounds have an ED 50 of less than 5 mg/kg in the "maximal electroshock" test described below.

根据本发明的一个特定方面，这些化合物在下面所述的“电癫痫发作-阈值试验”和“化学癫痫发作-阈值试验”中具有小于5mg/kg的ED50。According to a particular aspect of the invention, these compounds have an ED50 of less than 5 mg/kg in the "Electrical Seizure-Threshold Test" and "Chemical Seizure-Threshold Test" described below.

一些化合物有很少的或者没有临床副作用。因此，在该化合物不需要的镇静、降温和共济失调作用的模型中对一些化合物进行了试验。Some compounds have few or no clinical side effects. Accordingly, some compounds were tested in models of the compound's unwanted sedative, hypothermic and ataxic effects.

一些化合物具有抗惊厥功效和副作用如运动活性受损或共济失调作用如通过旋转杆上的行为测量所表现出的共济失调作用间的高治疗指数。这意味着预期这些化合物将可以被患者良好耐受，从而使得在观察到副作用之前可以使用高剂量。因此，预期对该治疗有良好的顺从性并且允许进行高剂量给药使得可以对使用其它药物将具有副作用的患者进行更有效的治疗。Some compounds have a high therapeutic index between anticonvulsant efficacy and side effects such as impaired locomotor activity or ataxic effects as demonstrated by behavioral measurements on a rotarod. This means that these compounds are expected to be well tolerated by patients, allowing high doses to be used before side effects are observed. Therefore, good compliance with the treatment is expected and allows high dosing to allow more effective treatment of patients who would have side effects with other drugs.

定义definition

术语杂原子指的是氮、氧或硫原子。The term heteroatom refers to nitrogen, oxygen or sulfur atoms.

卤素指的是氟、氯、溴或碘。Halogen refers to fluorine, chlorine, bromine or iodine.

C1-6-烷(链烯/炔)基和C1-6-(链烷/链烯/炔)基的表述指的是C1-6-烷基、C2-6-链烯基或C2-6-炔基。The expressions C 1-6 -alk(en/alkyn)yl and C 1-6 -(alk/alken/alkyn)yl refer to C 1-6 -alkyl, C 2-6 -alkenyl or C 2-6 -alkynyl.

术语C1-6-烷基指的是具有1至6个碳原子的支链或无支链的烷基，非限制性地包括甲基、乙基、1-丙基、2-丙基、1-丁基、2-丁基、2-甲基-2-丙基和2-甲基-1-丙基。The term C 1-6 -alkyl refers to branched or unbranched alkyl groups having from 1 to 6 carbon atoms, including without limitation methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methyl-2-propyl and 2-methyl-1-propyl.

同样，C2-6-链烯基和C2-6-炔基分别指定的是具有2至6个碳原子并分别包括一个双键和一个三键的该类基团，非限制性地包括乙烯基、丙烯基、丁烯基、乙炔基、丙炔基和丁炔基。Likewise, C 2-6 -alkenyl and C 2-6 -alkynyl respectively designate such groups having 2 to 6 carbon atoms and comprising one double bond and one triple bond respectively, including without limitation Vinyl, propenyl, butenyl, ethynyl, propynyl, and butynyl.

C1-3-烷(链烯/炔)基的表述指的是C1-3-烷基、C2-3-链烯基或C2-3-炔基。The expression C 1-3 -alk(en/yn)yl refers to C 1-3 -alkyl, C 2-3 -alkenyl or C 2-3 -alkynyl.

术语C1-3-烷基指的是具有1至3个碳原子的支链或无支链的烷基，非限制性地包括甲基、乙基、1-丙基和2-丙基。The term C 1-3 -alkyl refers to branched or unbranched alkyl groups having 1 to 3 carbon atoms, including without limitation methyl, ethyl, 1-propyl and 2-propyl.

同样，C2-3-链烯基和C2-3-炔基分别指的是具有2至3个碳原子，分别包括一个双键和一个三键的该类基团，非限制性地包括乙烯基、丙烯基、乙炔基和丙炔基。Likewise, C 2-3 -alkenyl and C 2-3 -alkynyl refer respectively to such groups having 2 to 3 carbon atoms, including one double bond and one triple bond respectively, including without limitation Vinyl, propenyl, ethynyl and propynyl.

C3-8-环烷(链烯)基和C3-8-环(烷/链烯)基的表述指的是C3-8-环烷基-或环链烯基。The expressions C 3-8 -cycloalk(en)yl and C 3-8 -cyclo(alk/alken)yl refer to C 3-8 -cycloalkyl- or cycloalkenyl.

术语C3-8-环烷基指的是具有3至8个C-原子的单环或二环碳环，非限制性地包括环丙基、环戊基、环己基等等。The term C 3-8 -cycloalkyl refers to monocyclic or bicyclic carbocycles having 3 to 8 C-atoms, including without limitation cyclopropyl, cyclopentyl, cyclohexyl and the like.

C3-6-环烷(链烯)基和C3-6-环(烷/链烯)基的表述指的是C3-6-环烷基-或环链烯基。The expressions C 3-6 -cycloalk(en)yl and C 3-6 -cyclo(alk/alken)yl refer to C 3-6 -cycloalkyl- or cycloalkenyl.

术语C3-6-环烷基指的是具有3至6个C-原子的单环或二环的碳环，非限制性地包括环丙基、环戊基、环己基等等。The term C 3-6 -cycloalkyl refers to a monocyclic or bicyclic carbocycle having 3 to 6 C-atoms, including without limitation cyclopropyl, cyclopentyl, cyclohexyl and the like.

术语C3-8-环链烯基指的是具有3至8个C-原子并包括一个双键的单环或二环碳环。The term C 3-8 -cycloalkenyl refers to monocyclic or bicyclic carbocycles having 3 to 8 C-atoms and including one double bond.

术语杂环烷(链烯)基指的是其中所说的环是由5至8个选自碳原子和杂原子的原子形成的环的单环或二环环系；前提是所说形成环的原子中的一个或两个是独立选择的杂原子。因此，术语杂环烷(链烯)基可能指的是其中所说的环是由5至8个选自3-7个碳原子和1或2个选自N、S、或O的杂原子的原子形成的环的单环或二环环系。该类环系的实例有吗啉、吡咯烷、哌啶和哌嗪。The term heterocycloalk(en)yl means a monocyclic or bicyclic ring system in which said ring is a ring formed by 5 to 8 atoms selected from carbon atoms and heteroatoms; provided that said ring One or two of the atoms in are independently selected heteroatoms. Thus, the term heterocycloalk(en)yl may refer to those in which said ring is composed of 5 to 8 heteroatoms selected from 3-7 carbon atoms and 1 or 2 heteroatoms selected from N, S, or O A monocyclic or bicyclic ring system of rings formed by atoms. Examples of such ring systems are morpholine, pyrrolidine, piperidine and piperazine.

术语卤代-C1-6-烷(链烯/炔)基指的是被一个或多个卤素原子取代的C1-6-烷(链烯/炔)基，非限制性地包括三氟甲基。同样，卤代-C3-8-环烷(链烯)基指的是被一个或多个卤素原子取代的C3-8-环烷(链烯)基，卤代-杂环烷(链烯)基指的是被一个或多个卤素原子取代的杂环烷(链烯)基。The term halo-C 1-6 -alk(en/yn)yl refers to C 1-6 -alk(en/yn)yl substituted by one or more halogen atoms, including without limitation trifluoro methyl. Likewise, halo-C 3-8 -cycloalkan(en)yl refers to C 3-8 -cycloalk(en)yl substituted by one or more halogen atoms, halo-heterocycloalk(en)yl Alken)yl refers to a heterocycloalk(en)yl group substituted with one or more halogen atoms.

术语NR10R10′-C1-6-烷(链烯/炔)基指的是被NR10R10′取代的C1-6-烷(链烯/炔)基；NR12R12′-C1-6-烷(链烯/炔)基指的是被NR12R12′取代的C1-6-烷(链烯/炔)基；和NR7R7′-C1-6-烷(链烯/炔)基指的是被NR7R7′取代的C1-6-烷(链烯/炔)基。2-氨基-4-甲基-戊烷是该类基团的一个实例，该实例不是用于进行限制。The term NR 10 R 10′ -C 1-6 -alk(en/alkyn)yl refers to C 1-6 -alk(en/alkyn)yl substituted by NR 10 R 10′ ; NR 12 R 12′ -C 1-6 -alk(en/alkyn)yl refers to C 1-6 -alk(en/alkyn)yl substituted by NR 12 R 12' ; and NR 7 R 7' -C 1-6 -Alk(en/yn)yl refers to C 1-6 -alk(en/yn)yl substituted by NR 7 R 7′ . 2-Amino-4-methyl-pentane is an example of such a group, which example is not intended to be limiting.

术语NR10R10′-C3-8-环烷(链烯)基指的是被NR10R10′取代的C3-8-环烷(链烯)基；NR12R12′-C3-8-环烷(链烯)基指的是被NR12R12′取代的C3-8-环烷(链烯)基；和NR7R7′-C3-8-环烷(链烯)基指的是被NR7R7′取代的C3-8-环烷(链烯)基。1-氨基-环丙烷是该类基团的一个实例，该实例不是用于进行限制。The term NR 10 R 10' -C 3-8 -cycloalk(en)yl refers to C 3-8 -cycloalk(en)yl substituted by NR 10 R 10' ; NR 12 R 12' -C 3-8 -cycloalk(en)yl refers to C 3-8 -cycloalk(en)yl substituted by NR 12 R 12′ ; and NR 7 R 7′ -C 3-8 -cycloalk( Alken)yl refers to C 3-8 -cycloalk(en)yl substituted by NR 7 R 7′ . 1-Amino-cyclopropane is an example of such a group, which example is not intended to be limiting.

术语NR10R10′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基指的是被NR10R10′取代的C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基；NR12R12′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基指的是被NR12R12′取代的C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基；和NR7R7′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基指的是被NR7R7′取代的C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基。The term NR 10 R 10′ -C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl refers to a C 3-8 -ring substituted by NR 10 R 10′ Alk(en)yl-C 1-6 -alk(en/alkyn)yl; NR 12 R 12' -C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn) Alkynyl refers to C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl substituted by NR 12 R 12′ ; and NR 7 R 7′ -C 3 -8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl refers to C 3-8 -cycloalk(en)yl-C 1 substituted by NR 7 R 7′ -6 -Alk(en/alkyn)yl.

当NR12R12′-C1-6-烷(链烯/炔)基、NR12R12′-C3-8-环烷(链烯)基、NR12R12′-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基中的任何一个任选地被取代时，C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基任选地被一个或多个独立地选自C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基或Ar的取代基所取代。When NR 12 R 12′ -C 1-6 -alk(alkene/alkynyl) group, NR 12 R 12′ -C 3-8 -cycloalkane(alkene) group, NR 12 R 12′ -C 3-8 -Cycloalk(alkene)yl-C 1-6 -alk(alkene/alkyn)yl, when any one is optionally substituted, C 1-6 -alk(alkene/alkynyl)yl, C 3- 8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn) are optionally selected from one or more independently selected from C 1 -6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyne) Substituents or substituents of Ar.

这里所用的术语酰基指的是甲酰基、C1-6-烷(链烯/炔)基羰基、C3-8-环烷(链烯)基羰基、Ar-羰基、Ar-C1-6-烷(链烯/炔)基羰基或C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基-羰基，其中C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基和Ar的定义如上所述。The term acyl as used herein refers to formyl, C 1-6 -alk(en/alkyn)ylcarbonyl, C 3-8 -cycloalk(en)ylcarbonyl, Ar-carbonyl, Ar-C 1-6 -alk(en/yn)ylcarbonyl or C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl-carbonyl, wherein C 1-6 -alk(alkene) /alkynyl) group, C 3-8 -cycloalkan(en)yl group and Ar are as defined above.

当两个取代基与氮原子一起形成一种5-8员饱和或不饱和的任选地包含一个另外的杂原子的环时，则一种单环环系是由5至8个原子所形成的，一个或两个所说的原子是选自N、S、或S的杂原子。该类环系的实例有吡咯烷、哌啶、哌嗪、吗啉、吡咯、噁唑烷、噻唑烷、咪唑烷、氮杂环丁烷、β-内酰胺、四唑和吡唑。A monocyclic ring system is formed by 5 to 8 atoms when two substituents form together with the nitrogen atom a 5-8 membered saturated or unsaturated ring optionally containing an additional heteroatom Yes, one or both of said atoms are selected from N, S, or S heteroatoms. Examples of such ring systems are pyrrolidine, piperidine, piperazine, morpholine, pyrrole, oxazolidine, thiazolidine, imidazolidine, azetidine, β-lactam, tetrazole and pyrazole.

当两个毗邻的取代基和其与之相连的芳族基团一起形成一种任选地包含一个或两个另外的杂原子的5-8员环时，则该环是由5-8个选自3-8个碳原子和0-2个选自N、S、或O和的杂原子的原子所形成的。该类两个毗邻的取代基可以一起形成：-(CH2)-CH2-、-CH＝CH-(CH2)m″-、-CH2-CH＝CH-(CH2)p″、-CH＝CH-CH＝CH-、-(CH2)n″-O-、-O-(CH2)m″-O-、-CH2-O-(CH2)p″-O-、-CH2-O-CH2-O-CH2-、-(CH2)n″-S-、-S-(CH2)m″-S-、-CH2-S-(CH2)p″-S-、-CH2-S-CH2-S-CH2-、-(CH2)n″-NH-、-NH-(CH2)m″-NH-、-CH2-NH-(CH2)n″-NH-、-CH＝CH-NH-、-O-(CH2)m″-NH-、-CH2-O-(CH2)p′-NH-或-O-(CH2)p″-NH-CH2-、-S-(CH2)m″-NH-、-N＝CH-NH-、-N-CH-O-或-N-CH-S-，其中m″是1、2或3，n″是2、3或4和p″是1或2。When two adjacent substituents and the aromatic groups to which they are attached form together a 5-8 membered ring optionally containing one or two additional heteroatoms, then the ring is composed of 5-8 Formed by atoms selected from 3-8 carbon atoms and 0-2 heteroatoms selected from N, S, or O. Two adjacent substituents of this type can be formed together: -(CH 2 )-CH 2 -, -CH=CH-(CH 2 ) m″ -, -CH 2 -CH=CH-(CH 2 ) p″ , -CH=CH-CH=CH-, -(CH 2 ) n" -O-, -O-(CH 2 ) m" -O-, -CH 2 -O-(CH 2 ) p" -O-, -CH 2 -O-CH 2 -O-CH 2 -, -(CH 2 ) n″ -S-, -S-(CH 2 ) m″ -S-, -CH 2 -S-(CH 2 ) p " -S-, -CH 2 -S-CH 2 -S-CH 2 -, -(CH 2 ) n" -NH-, -NH-(CH 2 ) m" -NH-, -CH 2 -NH- (CH 2 ) n″ -NH-, -CH=CH-NH-, -O-(CH 2 ) m″ -NH-, -CH 2 -O-(CH 2 ) p′ -NH- or -O- (CH 2 ) p″ -NH-CH 2 -, -S-(CH 2 ) m″ -NH-, -N=CH-NH-, -N-CH-O- or -N-CH-S-, wherein m" is 1, 2 or 3, n" is 2, 3 or 4 and p" is 1 or 2.

术语Ar指的是任选地被取代的5-10个碳原子的芳族系统，其中0、1、2、3或4个碳原子可以被独立地选自N、S、或O的杂原子所替换。该类Ar基团的实例有任选地被取代的苯基、任选地被取代的萘基(naphtyl)、任选地被取代的喹啉、任选地被取代的吲哚、任选地被取代的吡啶、任选地被取代的嘧啶、任选地被取代的噻吩、任选地被取代的呋喃、任选地被取代的噻唑和任选地被取代的噁唑。该类任选地被取代的Ar基可以被一个或多个独立地选自羟基、卤素、C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基、C3-8-烷(链烯/炔)氧基、酰基、硝基、氰基、-CO-NH-C1-6-烷(链烯/炔)基、-CO-N(C1-6-烷(链烯/炔)基)2、-NH2、-NH-C1-6-烷(链烯/炔)基、N(C1-6-烷(链烯/炔)基)2、S-C1-6-烷(链烯/炔)基、-SO2N(C1-6-烷(链烯/炔)基)2和-SO2NH-C1-6-烷(链烯/炔)基、SO2-C1-6-烷(链烯/炔)基和SO2O-C1-6-烷(链烯/炔)基的取代基所取代；或两个毗邻的取代基可以与该芳族基团一起形成一种任选地包含一个或两个杂原子并且可以是饱和或不饱和的5-8员环。The term Ar refers to an optionally substituted aromatic system of 5-10 carbon atoms, wherein 0, 1, 2, 3, or 4 carbon atoms may be independently selected from N, S, or O heteroatoms replaced. Examples of such Ar groups are optionally substituted phenyl, optionally substituted naphtyl, optionally substituted quinoline, optionally substituted indole, optionally Substituted pyridine, optionally substituted pyrimidine, optionally substituted thiophene, optionally substituted furan, optionally substituted thiazole, and optionally substituted oxazole. Such optionally substituted Ar groups may be replaced by one or more groups independently selected from hydroxyl, halogen, C 1-6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl , C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, halo-C 1-6 -alk(en/alkyn)yl, C 1-6 - Alk(alkene/alkynyl)oxy, C 3-8 -alk(en/alkynyl)oxy, acyl, nitro, cyano, -CO-NH-C 1-6 -alk(alkene/alkyne) -CO-N(C 1-6 -alk(en/alkyn)yl) 2 , -NH 2 , -NH-C 1-6 -alk(en/alkynyl)yl, N(C 1-6 -Alk(en/yn)yl) 2 , SC 1-6 -Alk(en/yn)yl, -SO 2 N(C 1-6 -Alk(en/yn)yl) 2 and -SO 2 Substitution of NH-C 1-6 -alk(en/yn)yl, SO 2 -C 1-6 -alk(en/yn)yl and SO 2 OC 1-6 -alk(en/yn)yl or two adjacent substituents may form together with the aromatic group a 5-8 membered ring optionally containing one or two heteroatoms and which may be saturated or unsaturated.

术语C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、C1-6-烷(链烯/炔)基-杂环烷(链烯)基、Ar、Ar-C1-6-烷(链烯/炔)基、Ar-C3-8-环烷(链烯)基、Ar-杂环烷(链烯)基、Ar-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、Ar-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、C1-6-烷(链烯/炔)氧基、C2-6-链烯氧基、C2-6-炔氧基、C3-8-环烷(链烯)氧基、C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)氧基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-C3-8-环烷(链烯)基、C1-6-烷(链烯/炔)氧基-杂环烷(链烯)基、Ar氧基-C1-6-烷(链烯/炔)基、Ar-C1-6-烷(链烯/炔)氧基-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)基羰基、C3-8-烷(链烯)基羰基、Ar-羰基、Ar-C1-6-烷(链烯)基羰基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基羰基、-CO-C1-6-烷(链烯/炔)基、S-C1-6-烷(链烯/炔)基、SO2-C1-6-烷(链烯/炔)基和SO2O-C1-6-烷(链烯/炔)基、C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)氧基-羰基-C1-6-烷(链烯/炔)基、C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)氧基-羰基-C1-6-烷(链烯/炔)基、酰基、酰基-C1-6-烷(链烯/炔)基、酰基-C3-8-烷(链烯)基、酰基-杂环烷(链烯)基、酰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、酰基-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、酰基-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、羟基-C1-6-烷(链烯/炔)基、羟基-C3-8-环烷(链烯)基、羟基-杂环烷(链烯)基、羟基-C3-8-环烷(链烯)基-C1-6-环烷(链烯/炔)基、羟基-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、羟基-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-环烷(链烯)基、卤代-杂环烷(链烯)基、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、卤代-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基-杂环烷(链烯)基、卤代-C1-6-烷(链烯/炔)基-Ar、卤代-C3-8-环烷(链烯)基-Ar、卤代-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基-Ar、卤代-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基-Ar、卤代-杂环烷(链烯)基-Ar、氰基-C1-6-烷(链烯/炔)基、氰基-C3-8-环烷(链烯)基、氰基-杂环烷(链烯)基、氰基-C3-8-环烷(链烯)基-C1-6-烷(链烯/炔)基、氰基-C1-6-烷(链烯/炔)基-C3-8-环烷(链烯)基、氰基-C1-6-烷(链烯/炔)基-杂环烷(链烯)基等等指的是其中C1-6-烷(链烯/炔)基、C2-6-链烯基、C2-6-炔基、C3-8-环烷(链烯)基、杂环烷(链烯)基、Ar、氰基、卤代-C1-6-烷(链烯/炔)基、卤代-C3-8-氰基烷(链烯)基、卤代-杂环烷(链烯)基和酰基的定义如上所述之类的基团。The terms C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalkane( Alken)yl, C 1-6 -alk(en/alkyn)yl-heterocycloalkan(en)yl, Ar, Ar-C 1-6 -alk(en/alkyn)yl, Ar-C 3 -8 -cycloalk(en)yl, Ar-heterocycloalk(en)yl, Ar-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl , Ar-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(alkene)yl, Ar-C 1-6 -alk(en/alkyn)yl-heterocycloalkane( Alken)yl, C 1-6 -alk(alkene/alkynyl)oxy, C 2-6 -alkenyloxy, C 2-6 -alkynyloxy, C 3-8 -cycloalkane(alkene) Oxygen, C 1-6 -alk(alkene/alkynyl)oxy-C 1-6 -alk(en/alkynyl)yl, C 3-8 -cycloalkane(alkenyl)oxyl-C 1-6 -alk(en/alkyn)yl, C 1-6 -alk(en/alkyn)oxy-C 3-8 -cycloalk(en)yl, C 1-6 -alk(en/alkyn) Oxy-heterocycloalkane(alkene)yl, Aroxy-C 1-6 -alk(alkene/alkyne)yl, Ar-C 1-6 -alk(alkene/alkynyl)oxy-C 1- 6 -alk(en/alkyn)yl, C 1-6 -alk(alken/alkyn)ylcarbonyl, C 3-8 -alk(en)ylcarbonyl, Ar-carbonyl, Ar-C 1-6- Alk(en)ylcarbonyl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyne)ylcarbonyl, -CO-C 1-6 -alk(en/alkyne) ) group, SC 1-6 -alk(en/alkyn)yl, SO 2 -C 1-6 -alk(en/alkyn)yl and SO 2 OC 1-6 -alk(en/alkyn)yl, C 1-6 -alk(alkene/alkynyl)oxy-carbonyl-C 1-6 -alk(en/alkynyl)yl, C 3-8 -cycloalkane(alkenyl)oxy-carbonyl-C 1- 6 -alk(en/alkyn)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)oxy-carbonyl-C 1-6 -alk(alkene) /alkyn)yl, acyl, acyl-C 1-6 -alk(en/alkyn)yl, acyl-C 3-8 -alk(en)yl, acyl-heterocycloalkane(en)yl, acyl- C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, acyl-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalkane (alkene) group, acyl-C 1-6 -alk(alkene/alkyne)yl-heterocycloalkane(alkene)yl, hydroxyl-C 1-6 -alk(alkene/alkynyl)yl, hydroxyl-C 3-8 -Cycloalkane(alkene)yl, Hydroxy-Heterocycloalkane(alkene)yl, Hydroxy-C 3-8 -Cycloalkane(alkene)yl-C 1-6 -Cycloalkane(alkene/alkyne ) group, Hydroxy-C 1-6 -alk(alkene/alkyne)yl-C 3-8 -cycloalkane(en)yl, Hydroxy-C 1-6 -alk(alkene/alkynyl)yl-heterocycle Alk(en)yl, Halo-C 1-6 -Alk(en/Alkyn)yl, Halo-C 3-8 -Cycloalk(alken)yl, Halo-Heterocycloalk(en)yl Base, Halo-C 3-8 -Cycloalkane(alkene)yl-C 1-6 -Alk(alkene/alkynyl)yl, Halo-C 1-6 -Alk(alkene/alkynyl)yl-C 3-8 -cycloalk(en)yl, halo-C 1-6 -alk(en/alkyn)yl-heterocycloalk(alken)yl, halo-C 1-6 -alk(alkene) /alkyn)yl-C 3-8 -cycloalk(en)yl, halo-C 1-6 -alk(en/alkyn)yl-heterocycloalk(en)yl, halo-C 1- 6 -alk(en/alkyn)yl-Ar, halo-C 3-8 -cycloalk(en)yl-Ar, halo-C 3-8 -cycloalk(en)yl-C 1- 6 -alk(en/alkyn)yl-Ar, halo-C 1-6 -alk(en/alkyn)yl-C 3-8 -cycloalk(en)yl-Ar, halo-heterocycle Alk(en)yl-Ar, cyano-C 1-6 -alk(en/alkyn)yl, cyano-C 3-8 -cycloalk(alken)yl, cyano-heterocycloalkane(chain En)yl, cyano-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/alkyn)yl, cyano-C 1-6 -alk(en/alkyn)yl -C 3-8 -cycloalk(en)yl, cyano-C 1-6 -alk(en/alkyn)yl-heterocycloalk(en)yl, etc. refer to wherein C 1-6 - Alk(en/alkyn)yl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-8 -cycloalk(en)yl, heterocycloalk(en)yl, Ar, Cyano, halo-C 1-6 -alk(en/alkyn)yl, halo-C 3-8 -cyanoalk(en)yl, halo-heterocycloalk(en)yl and acyl A group such as that defined above.

本发明的盐优选地是可药用的盐。该类盐包括可药用的酸加成盐、可药用的金属盐、铵盐和烷化铵盐。The salts of the present invention are preferably pharmaceutically acceptable salts. Such salts include pharmaceutically acceptable acid addition salts, pharmaceutically acceptable metal salts, ammonium salts and alkylated ammonium salts.

本发明可药用的盐优选地是酸加成盐。本发明的酸加成盐优选地是本发明化合物与无毒的酸形成的可药用盐。酸加成盐包括无机酸以及有机酸的盐。The pharmaceutically acceptable salts of the present invention are preferably acid addition salts. The acid addition salts of the invention are preferably pharmaceutically acceptable salts of the compounds of the invention with non-toxic acids. Acid addition salts include salts of inorganic acids as well as organic acids.

适宜无机酸的典型实例包括盐酸、氢溴酸、氢碘酸、硫酸、氨基磺酸、磷酸和硝酸等等。可以用本领域技术人员公知的方法来形成该类酸加成盐。可药用无机或有机酸加成盐的另外的实例包括在J.Pharm.Sci.1977，66，2(其在这里被引入作为参考)中所列的可药用盐。Typical examples of suitable inorganic acids include hydrochloric, hydrobromic, hydroiodic, sulfuric, sulfamic, phosphoric, and nitric acids, and the like. Such acid addition salts can be formed by methods well known to those skilled in the art. Further examples of pharmaceutically acceptable inorganic or organic acid addition salts include the pharmaceutically acceptable salts listed in J. Pharm. Sci. 1977, 66, 2 (which is hereby incorporated by reference).

适宜有机酸的典型实例包括醋酸、三氯醋酸、三氟醋酸、丙酸、苯甲酸、肉桂酸、枸橼酸、富马酸、乙醇酸、乳酸、马来酸、苹果酸、丙二酸、苦杏仁酸、草酸、苦味酸、丙酮酸、水杨酸、琥珀酸、乙磺酸、酒石酸、抗坏血酸、扑酸、葡萄糖酸、宁糠酸、天门冬氨酸、硬脂酸、棕榈酸、EDTA、乙醇酸、对-氨基苯甲酸、谷氨酸、二-亚甲基水杨酸、甲磺酸、乙烷二磺酸、衣康酸、苯磺酸、对-甲苯磺酸、茶碱乙酸、以及8-卤代茶碱，例如8-溴茶碱等等。可药用的无机酸或有机酸加成盐的另外的实例包括J.Pharm.Sci.1977，66，2(其在这里被引入作为参考)中所列的可药用盐。Typical examples of suitable organic acids include acetic acid, trichloroacetic acid, trifluoroacetic acid, propionic acid, benzoic acid, cinnamic acid, citric acid, fumaric acid, glycolic acid, lactic acid, maleic acid, malic acid, malonic acid, Mandelic acid, oxalic acid, picric acid, pyruvic acid, salicylic acid, succinic acid, ethanesulfonic acid, tartaric acid, ascorbic acid, pamoic acid, gluconic acid, furoic acid, aspartic acid, stearic acid, palmitic acid, EDTA , glycolic acid, p-aminobenzoic acid, glutamic acid, di-methylene salicylic acid, methanesulfonic acid, ethanedisulfonic acid, itaconic acid, benzenesulfonic acid, p-toluenesulfonic acid, theophylline acetic acid , and 8-halogenated theophylline, such as 8-bromotheophylline and the like. Further examples of pharmaceutically acceptable inorganic acid or organic acid addition salts include the pharmaceutically acceptable salts listed in J. Pharm. Sci. 1977, 66, 2 (which is hereby incorporated by reference).

金属盐的实例包括锂、钠、钾、镁盐等等。Examples of metal salts include lithium, sodium, potassium, magnesium salts and the like.

铵盐和烷化铵盐的实例包括铵、甲基-、二甲基-、三甲基-、乙基-、羟基乙基-、二乙基-、正-丁基-、仲-丁基、叔-丁基-、四甲基铵盐等等。Examples of ammonium and alkylated ammonium salts include ammonium, methyl-, dimethyl-, trimethyl-, ethyl-, hydroxyethyl-, diethyl-, n-butyl-, sec-butyl , tert-butyl-, tetramethylammonium salt, etc.

就可药用的酸加成盐而言，还有本发明化合物能形成的水合物。As pharmaceutically acceptable acid addition salts there are also hydrates which the compounds according to the invention are able to form.

本发明的化合物可具有一个或多个不对称中心，在被分离时，任何光学异构体、纯或部分纯化的光学异构体其或外消旋混合物都被包括在本发明的范围内。The compounds of the present invention may possess one or more asymmetric centers and, when isolated, any optical isomers, pure or partially purified optical isomers or racemic mixtures thereof, are included within the scope of the present invention.

此外，当在分子中存在双键或完全饱和或部分饱和环系时，可以形成几何异构体。在分离时，本发明范围内包括任何几何异构体、纯或部分纯化的几何异构体或其混合物。同样，具有旋转受限键的分子可以形成几何异构体。其也被包括在本发明的范围内。In addition, geometric isomers may form when double bonds or fully saturated or partially saturated ring systems are present in the molecule. When isolated, any geometric isomers, pure or partially purified geometric isomers or mixtures thereof, are included within the scope of the present invention. Likewise, molecules with rotationally restricted bonds can form geometric isomers. It is also included in the scope of the present invention.

此外，一些本发明的化合物可以以不同的互变异构形式存在并且这些化合物能形成的任何互变异构形式也被包括在本发明的范围内。Furthermore, some of the compounds of the present invention may exist in different tautomeric forms and any tautomeric forms these compounds are capable of forming are also included within the scope of the present invention.

本发明的化合物可以以未溶剂化形式以及具有溶剂如水、乙醇等等溶剂的溶剂化形式存在。对于本发明的目的而言，一般认为该溶剂化形式与未溶剂化形式等效。The compounds of the present invention can exist in unsolvated as well as solvated forms with solvents such as water, ethanol, and the like. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the present invention.

一些本发明的化合物包含手性中心并且该类化合物以异构体(即对映异构体)形式存在。本发明包括所有该类异构体及其包括外消旋混合物在内的任何混合物。Some of the compounds of the present invention contain chiral centers and such compounds exist as isomers (ie, enantiomers). The present invention includes all such isomers and any mixtures thereof including racemic mixtures.

可以用已知的方法，例如通过用光学活性酸对其非对映体盐进行分离并用碱进行处理从而释放该光学活性的胺化合物来对外消旋体形式进行拆分。另一种将外消旋体拆分成光学对映体的方法是以使用光学活性基质的色谱为基础的。例如，还可以用d-或1-(酒石酸盐、苦杏仁酸盐或樟脑磺酸盐)盐分级结晶来将本发明外消旋的化合物拆分成其光学异构体。还可以通过形成非对映体衍生物来对本发明的化合物进行拆分。Resolution of the racemic forms can be carried out by known methods, for example by separation of the diastereomeric salts with an optically active acid and treatment with a base to release the optically active amine compound. Another method for the resolution of racemates into optical antipodes is based on chromatography using optically active matrices. For example, fractional crystallization of d- or 1-(tartrate, mandelate or camphorsulfonate) salts can also be used to resolve racemic compounds of the invention into their optical isomers. The compounds of the invention can also be resolved by the formation of diastereomeric derivatives.

可以用本领域技术人员公知的拆分光学异构体的另外的方法。该类方法包括J.Jaques，A.Collet和S.Wilen在“对映异构体、外消旋体、和拆分(Enantiomers，Racemates，和Resolutiohs)”，John Wiley和Sons，纽约(1981)中所讨论的这些方法。Additional methods of resolution of optical isomers known to those skilled in the art may be used. Such methods include J. Jaques, A. Collet and S. Wilen in "Enantiomers, Racemates, and Resolutions (Enantiomers, Racemates, and Resolutiohs)", John Wiley and Sons, New York (1981) The methods discussed in .

还可以由光学活性起始材料来制备这些光学活性的化合物。These optically active compounds can also be prepared from optically active starting materials.

本发明还包括在给药时通过代谢过程进行化学转化，然后变成药理学活性物质的本发明化合物的前体药物。该类前体药物通常是通式I、XXIX、XXX、XXXI、XXXII或XXXIII的化合物的官能衍生物，其在体内可以容易地转化成式I、XXIX、XXX、XXXI、XXXII或XXXIII的化合物。在例如“前体药物设计(Design of Prodrugs)”，H.Bundgaard主编，Elsevier，1985中对选择和制备适宜前体药物衍生物的常规方法进行了描述。The present invention also includes prodrugs of the compounds of the present invention which are chemically converted by metabolic processes upon administration and then become pharmacologically active substances. Such prodrugs are generally functional derivatives of compounds of general formula I, XXIX, XXX, XXXI, XXXII or XXXIII, which can be easily converted into compounds of formula I, XXIX, XXX, XXXI, XXXII or XXXIII in vivo. General methods for selecting and preparing suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. H. Bundgaard, Elsevier, 1985.

本发明还包括本发明化合物的活性代谢物。The present invention also includes active metabolites of the compounds of the present invention.

不管何时，在涉及式I、XXIX、XXX、XXXI、XXXII或XXXIII的化合物时，术语癫痫(epilepsy和epilepsies)包括在InternationalLeague Against epilepsy：癫痫发作的临床修正方案和脑电图学分类(Proposal for revised clinical and electroencephalographicclassification of seizures)，Commission on Classification andTerminology of the International League AgainstEpilepsy.Epilepsia 1981 22：489-501和International LeagueAgainst Epilepsy：癫痫和痫症的分类修正方案(Proposal for revisedclassification of epilepsies and epileptic syndromes)，Commission on Classification and Terminology of theInternational League Against Epilepsy.Epilepsia193930(4)：389-399中被称为癫痫、痫症和癫痫性发作中的任何一种。Whenever referring to a compound of formula I, XXIX, XXX, XXXI, XXXII or XXXIII, the terms epilepsy and epilepsies are included in the International League Against epilepsy: Clinical Modification Protocol and Electroencephalographic Classification of Seizures (Proposal for revised clinical and electroencephalographicclassification of seizures)，Commission on Classification andTerminology of the International League AgainstEpilepsy.Epilepsia 1981 22：489-501和International LeagueAgainst Epilepsy：癫痫和痫症的分类修正方案(Proposal for revisedclassification of epilepsies and epileptic syndromes)，Commission on Classification and Terminology of the International League Against Epilepsy.Epilepsia193930(4):389-399 is referred to as any one of epilepsy, epilepsy and epileptic seizures.

不管何时，在涉及式I、XXIX、XXX、XXXI、XXXII或XXXIII的化合物时，术语焦虑障碍包括被称为恐慌发作、广场恐怖症、与广场恐怖症有关的恐慌病症、与广场恐怖症无关的恐慌病症、无恐慌病症史的广场恐怖症、特异恐怖、社交恐怖症、强迫症、创伤后应激障碍、急性应激障碍、泛化性焦虑症、由于一般性医学情况造成的焦虑障碍、物质诱导的焦虑障碍、离别焦虑障碍、适应性障碍和AmericanPsychiatric Association精神病症的诊断和统计学手册(Diagnosticand statistical manual of mental disorders)，第4版，1994：110-113、393-444和623-627定义的未特定说明的焦虑障碍的情况和疾病。Whenever referring to a compound of formula I, XXIX, XXX, XXXI, XXXII or XXXIII, the term anxiety disorder includes those known as panic attacks, agoraphobia, panic disorders associated with agoraphobia, not related to agoraphobia panic disorder, agoraphobia without history of panic disorder, specific phobia, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, acute stress disorder, generalized anxiety disorder, anxiety disorder due to a general medical condition, Substance-induced anxiety disorder, separation anxiety disorder, adjustment disorder, and American Psychiatric Association Diagnostic and statistical manual of mental disorders, 4th ed., 1994: 110-113, 393-444, and 623-627 Defined unspecified anxiety disorder conditions and disorders.

药物组合物pharmaceutical composition

本发明的化合物通常是以其游离碱或可药用盐的形式被使用的。其典型实例如上所述。The compounds of the present invention are generally used in the form of their free bases or pharmaceutically acceptable salts. Typical examples thereof are as described above.

如果需要的话，本发明的药物组合物可以包含式I的化合物和另外的药理学活性物质如前面所述的这些物质。The pharmaceutical compositions according to the invention may, if desired, comprise a compound of the formula I and further pharmacologically active substances such as those previously described.

本发明的化合物可以以单剂量或多剂量被单独给药或者与可药用的载体或赋形剂联合给药。可以根据常规技术如在Remington：TheScience and Practice of Pharmacy，19 Edition，Gennaro，Ed.，MackPublishing Co.，Easton，PA，1995中所公开的这些常规技术用可药用的载体或稀释剂以及任何其它已知助剂和赋形剂来对本发明的药物组合物进行配制。The compounds of the present invention may be administered alone or in combination with pharmaceutically acceptable carriers or excipients in single or multiple doses. A pharmaceutically acceptable carrier or diluent and any other pharmaceutically acceptable carrier or diluent may be used according to conventional techniques such as those disclosed in Remington: The Science and Practice of Pharmacy, 19 Edition, Gennaro, Ed., Mack Publishing Co., Easton, PA, 1995. The auxiliaries and excipients are known for formulating the pharmaceutical compositions of the invention.

可以将这些药物组合物制备成通过任何适宜途径进行给药的形式，如制备成通过口服、直肠、鼻、肺、局部(包括颊和舌下)、经皮、脑池内、腹膜内、阴道和胃肠外(包括皮下、肌内、鞘内、静脉内和真皮内)途径进行给药的形式，优选口服途径。应当意识到的是优选的途径将取决于被治疗个体的一般情况和年龄、被治疗情况的性质和所选择的活性成分。These pharmaceutical compositions may be prepared for administration by any suitable route, such as oral, rectal, nasal, pulmonary, topical (including buccal and sublingual), transdermal, intracisternal, intraperitoneal, vaginal and The form of administration by parenteral (including subcutaneous, intramuscular, intrathecal, intravenous and intradermal) routes, preferably oral route. It will be appreciated that the preferred route will depend upon the general condition and age of the individual being treated, the nature of the condition being treated and the active ingredient chosen.

用于口服给药的药物组合物包括固体剂型如胶囊、片剂、糖锭剂、丸剂、锭剂、粉剂和颗粒剂。在适宜的情况中，可以用包衣如肠包衣对其进行制备或者可以用现有技术中众所周知的方法对其进行制备从而提供活性成分的控释如缓释或长时间释放。Pharmaceutical compositions for oral administration include solid dosage forms such as capsules, tablets, dragees, pills, lozenges, powders and granules. Where appropriate, they may be prepared with coatings, such as enteric coatings, or may be prepared by methods well known in the art so as to provide controlled, eg sustained or prolonged release of the active ingredient.

用于口服给药的液体剂型包括溶液、乳剂、混悬液、糖浆和酏剂。Liquid dosage forms for oral administration include solutions, emulsions, suspensions, syrups and elixirs.

用于胃肠外给药的药物组合物包括无菌的水性或非水性可注射溶夜、分散体、混悬液或乳剂以及在使用前被重组成无菌可注射溶液或分散体的无菌粉末。认为可注射的储库制剂也在本发明的范围内。Pharmaceutical compositions for parenteral administration include sterile aqueous or nonaqueous injectable solutions, dispersions, suspensions or emulsions and sterile injectable solutions or dispersions that are reconstituted before use. powder. Injectable depot formulations are also considered to be within the scope of the present invention.

其它适宜给药的形式包括栓剂、喷雾剂、软膏、霜、凝胶、吸入剂、皮肤贴剂、植入物等等。Other suitable administration forms include suppositories, sprays, ointments, creams, gels, inhalants, skin patches, implants and the like.

本发明的药物组合物或根据本发明制备的这些组合物可以通过任何适宜途径进行给药，例如可以以片剂、胶囊、粉剂、糖浆等等形式口服给药、或以注射用溶液的形式胃肠外给药。对于该类组合物的制备而言，可以使用现有技术中众所周知的方法，并且可以使用任何可药用的载体、稀释剂、赋形剂或本领域常用的其它添加剂。The pharmaceutical composition of the present invention or these compositions prepared according to the present invention can be administered by any suitable route, such as oral administration in the form of tablets, capsules, powders, syrups, etc., or gastric administration in the form of solutions for injection Parenteral administration. For the preparation of such compositions, well-known methods in the prior art can be used, and any pharmaceutically acceptable carrier, diluent, excipient or other additives commonly used in the art can be used.

一种典型的口服剂量是每天以一个或多个剂量如1至3个剂量给药的约0.001至约100mg/kg体重，优选地为每天约0.01至约50mg/kg体重，并且更优选地为每天约0.05至约10mg/kg体重的剂量。精确剂量将取决于给药频率和方式、被治疗个体的性别、年龄、体重和一般情况、所治疗情况的性质和严重程度以及被治疗的任何共存疾病和对本领域技术人员而言显而易见的其它因素。A typical oral dose is about 0.001 to about 100 mg/kg body weight per day administered in one or more doses, such as 1 to 3 doses, preferably about 0.01 to about 50 mg/kg body weight per day, and more preferably Doses of about 0.05 to about 10 mg/kg body weight per day. The precise dosage will depend on the frequency and mode of administration, the sex, age, weight, and general condition of the individual being treated, the nature and severity of the condition being treated, and any co-morbidities being treated, and other factors apparent to those skilled in the art .

该制剂可以用本领域技术人员公知的方法以单位剂型形式存在。一种用于每天口服给药一次或多次如每天口服给药1至3次的典型单位剂型可包含0.05至约1000mg，优选约0.1至约500mg，并且更优选约0.5mg至约200mg。The formulations may be presented in unit dosage form by methods well known to those skilled in the art. A typical unit dosage form for oral administration one or more times per day, such as 1 to 3 times per day, may contain from 0.05 to about 1000 mg, preferably from about 0.1 to about 500 mg, and more preferably from about 0.5 mg to about 200 mg.

对于胃肠外途径如静脉内、鞘内、肌内给药和相似给药而言，典型剂量为口服给药所用剂量的大约一半。For parenteral routes such as intravenous, intrathecal, intramuscular and similar administration, typical dosages will be about one-half those used for oral administration.

本发明的化合物通常是以游离物质或其可药用盐的形式被使用的。一个实例是具有游离酸效用的化合物的碱加成盐。当本发明的化合物包含游离酸时，该类盐可以用常规方式通过用化学当量的可药用碱对本发明化合物游离酸的溶液或混悬液进行处理来进行制备。典型的实例如上所述。The compounds of the present invention are generally used in the form of the free substance or a pharmaceutically acceptable salt thereof. An example is a base addition salt of a compound that has the effect of the free acid. When a compound of the invention contains a free acid, such salts may be prepared in conventional manner by treating a solution or suspension of the free acid of the compound of the invention with a stoichiometric equivalent of a pharmaceutically acceptable base. Typical examples are as described above.

对于胃肠外给药而言，可以使用本发明的新型化合物在无菌水性溶液、水性丙二醇、水性维生素E或芝麻油或花生油中的溶液。如果必要的话，可以对该类水性溶液进行适宜缓冲并且首先用足够的盐水或葡萄糖使该液体稀释剂等渗。该水性溶液特别适用于静脉内、肌内、皮下和腹膜内给药。所用的无菌水性介质都可以容易地用本领域技术人员已知的标准技术获得。For parenteral administration, solutions of the novel compounds of the invention in sterile aqueous solution, aqueous propylene glycol, aqueous vitamin E or sesame or peanut oil may be employed. Such aqueous solutions may be suitably buffered if necessary and the liquid diluent first rendered isotonic with sufficient saline or glucose. The aqueous solutions are particularly suitable for intravenous, intramuscular, subcutaneous and intraperitoneal administration. All sterile aqueous media employed are readily obtainable by standard techniques known to those skilled in the art.

可以通过将活性成分和可能的添加剂溶解于一部分注射用溶剂，优选无菌水中，将该溶液调节至所需体积，将该溶液灭菌并将其填充到适宜的安瓿或小瓶中来制备注射用溶液。可以加入本领域常用的任何适宜添加剂，如等渗剂、防腐剂、抗氧剂等等。Injectables can be prepared by dissolving the active ingredient and possible additives in a portion of the solvent for injection, preferably sterile water, adjusting the solution to the desired volume, sterilizing the solution and filling it into suitable ampoules or vials solution. Any suitable additives commonly used in the art may be added, such as isotonic agents, preservatives, antioxidants and the like.

适宜的药用载体包括惰性固体稀释剂或填充剂、无菌的水性溶液和各种有机溶剂。Suitable pharmaceutical carriers include inert solid diluents or fillers, sterile aqueous solutions and various organic solvents.

固体载体的实例有乳糖、石膏粉、蔗糖、环糊精、滑石粉、琼脂、果胶、阿拉伯胶、硬脂酸和纤维素的低级烷基醚、玉米淀粉、马铃薯淀粉、滑石粉(talcum)、硬脂酸镁、明胶、乳糖、树胶等等。Examples of solid carriers are lactose, terra alba, sucrose, cyclodextrin, talc, agar, pectin, acacia, stearic acid and lower alkyl ethers of cellulose, corn starch, potato starch, talcum , magnesium stearate, gelatin, lactose, gum, etc.

可以使用常用于该类目的的任何其它助剂或添加剂如着色剂、矫味剂、防腐剂等等，前提是其可以与活性成分相容。Any other adjuvants or additives customary for such purposes such as colorants, flavors, preservatives etc. may be used provided that they are compatible with the active ingredients.

液体载体的实例有糖浆、花生油、橄榄油、磷脂、脂肪酸、脂肪酸胺、聚氧化乙烯和水。同样，该载体或稀释剂可包括现有技术中已知的任何缓释材料，如单独或混有蜡的单硬脂酸甘油酯或二硬脂酸甘油酯。Examples of liquid carriers are syrup, peanut oil, olive oil, phospholipids, fatty acids, fatty acid amines, polyethylene oxide and water. Likewise, the carrier or diluent may include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or with a wax.

然后，可以用适于所公开给药途径的各种剂型容易地将通过将本发明的新型化合物和可药用的载体相结合所形成的药物组合物进行给药。该制剂可以用药学领域已知的方法方便地以单位剂型形式存在。Pharmaceutical compositions formed by combining the novel compounds of this invention and pharmaceutically acceptable carriers can then be readily administered in a variety of dosage forms suitable for the disclosed routes of administration. The formulations may conveniently be presented in unit dosage form by methods known in the art of pharmacy.

本发明适于口服给药的制剂可以以离散单位如胶囊或片剂的形式存在，其各自包含预定数量的活性成分，并且其可包括一种或多种适宜的赋形剂。此外，可以口服获得的制剂还可以是粉末或颗粒、位于水性或非水性液体中的溶液或混悬液、水包油或油包水液体乳剂的形式。Formulations of the present invention suitable for oral administration may be presented as discrete units such as capsules or tablets, each containing a predetermined quantity of the active ingredient, and which may include one or more suitable excipients. Furthermore, the orally obtainable formulations may also be in the form of powders or granules, solutions or suspensions in aqueous or non-aqueous liquids, oil-in-water or water-in-oil liquid emulsions.

如果用固体载体来进行口服给药，则该制剂可以是以粉末形式被放置于硬明胶胶囊中的tablette、或小丸形式，或者其可以为糖锭或锭剂形式。If a solid carrier is used for oral administration, the preparation may be in powder form placed in a hard gelatin capsule, a tablettte, or pellets, or it may be in the form of a troche or lozenge.

该固体载体的数量可以在很宽的范围内进行变化，但是通常为约25mg至约1g。The amount of the solid carrier can vary widely but will generally be from about 25 mg to about 1 g.

如果使用液体载体，则该制剂可以是糖浆、乳剂、软明胶胶囊或无菌可注射液体如水性或非水性液体混悬液或溶液形式。If a liquid carrier is used, the preparation may be in the form of a syrup, emulsion, soft gelatin capsule or sterile injectable liquid such as an aqueous or non-aqueous liquid suspension or solution.

如果需要的话，本发明的药物组合物可以包含式I、XXIX、XXX、XXXII或XXXIII的化合物和另外的药理学活性物质如前面所公开的这些物质。The pharmaceutical compositions of the present invention may, if desired, comprise a compound of formula I, XXIX, XXX, XXXII or XXXIII and additional pharmacologically active substances such as those previously disclosed.

本发明制剂处方的典型实例如下：A typical example of the formulation prescription of the present invention is as follows:

1)包含5.0mg(以游离碱形式进行计算的)本发明化合物的片剂：1) A tablet containing 5.0 mg (calculated as the free base) of a compound of the invention:

式I、XXIX、XXX、XXXI、XXXII或XXXIII的化合物    5.0mgCompound of formula I, XXIX, XXX, XXXI, XXXII or XXXIII 5.0 mg

乳糖                                           60mgLactose 60mg

玉米淀粉                                       30mgcornstarch 30mg

羟丙基纤维素                                   2.4mgHydroxypropyl Cellulose 2.4mg

微晶纤维素                                     19.2mgMicrocrystalline Cellulose 19.2mg

A型交联羧甲基纤维素钠                          2.4mgCroscarmellose sodium type A 2.4mg

硬脂酸镁                                       0.84mgMagnesium stearate 0.84mg

2)包含0.5mg(以游离碱形式进行计算的)本发明化合物的片剂：2) Tablets containing 0.5 mg (calculated as free base) of a compound of the invention:

式I、XXIX、XXX、XXXI、XXXII或XXXIII的化合物    0.5mgCompound of Formula I, XXIX, XXX, XXXI, XXXII or XXXIII 0.5 mg

乳糖                                           46.9mgLactose 46.9mg

玉米淀粉                                       23.5mgCornstarch 23.5mg

聚维酮                                         1.8mgPovidone 1.8mg

微晶纤维素                                     14.4mgMicrocrystalline Cellulose 14.4mg

A型交联羧甲基纤维素钠                          1.8mgCroscarmellose sodium type A 1.8mg

硬脂酸镁                                       0.63mgMagnesium stearate 0.63mg

3)糖浆，其每毫升包含：3) Syrup containing per milliliter:

式I、XXIX、XXX、XXXI、XXXII或XXXIII的化合物    25mgCompound of formula I, XXIX, XXX, XXXI, XXXII or XXXIII 25mg

山梨醇                                         500mgSorbitol 500mg

羟丙基纤维素                                   15mgHydroxypropyl Cellulose 15mg

甘油                                           50mgGlycerin 50mg

尼泊金甲酯                                     1mgMethylparaben 1mg

尼泊金丙酯                                     0.1mgPropylparaben 0.1mg

乙醇                                           0.005mLEthanol 0.005mL

矫味剂                                         0.05mgFlavoring agent 0.05mg

糖精钠                                         0.5mgSodium saccharin 0.5mg

水                                             加至1mLAdd water to 1mL

4)注射用溶液，其每毫升包含：4) A solution for injection, which contains per milliliter:

式I、XXIX、XXX、XXXI、XXXII或XXXIII的化合物    0.5mgCompound of Formula I, XXIX, XXX, XXXI, XXXII or XXXIII 0.5 mg

山梨醇                                         5.1mgSorbitol 5.1mg

醋酸                                           0.05mgAcetic acid 0.05mg

糖精钠                        0.5mgSodium saccharin 0.5mg

水                            加至1mLAdd water to 1mL

本发明化合物的制备Preparation of compounds of the present invention

Figure A20048000750700931
Figure A20048000750700931

其中a、b、c、d、e、f、g、h、s、q、U、W、X、Z、R1、R2、R3、R5、R6、R6′、R7、R7′、R8、R9、R9′、R10、R10′、R11、R12和R12′的定义如式I下所述的本发明通式I的化合物可以用下面所述的方法和如流程图所示那样来进行制备。Where a, b, c, d, e, f, g, h, s, q, U, W, X, Z, R 1 , R 2 , R 3 , R 5 , R 6 , R 6′ , R 7 , R 7' , R 8 , R 9 , R 9' , R 10 , R 10' , R 11 , R 12 and R 12' are defined as follows in formula I. The compound of general formula I of the present invention can be used as follows The method and preparation are carried out as shown in the flow chart.

通式IX或XI的被取代的4-硝基苯胺可以通过商业途径获得、在文献中进行了描述或者可以根据本领域学人员所公知的方法来进行制备。s是0和R2是上面所定义的被取代的芳基或被取代的杂芳基如呋喃基、噻吩基、苯基、吡啶基的通式IX或XI的化合物特别是可以由R2是I或Br的相应化合物用本领域化学人员公知的交联-偶合反应如Suzuki偶合、Stille偶合、或其它过渡金属催化的交联-偶合反应[D.W.Knight，“sp2碳中心间的偶合反应”，Comprehensive OrganicSynthesis，第3版，第481-520页，Pergamon Press 1991]来进行制备。或者，通式IX或XI的4-硝基苯胺可以由被保护或未被保护形式的相应的2-取代的苯胺用本领域化学人员公知的硝化处理[R.Behnisch，“Aromatische Nitro-Verbindungen”，Methoden derOrganische Chemie/(Houben-Weyl)，第255页，v.E16d，Thieme：1992]来进行制备。这种方法特别是可用于其中U是S、SO2、或SO2NR11的通式IX或XI的化合物。还可以根据本领域化学人员公知的方法通过氧化将其中U是S的通式IX或XI的化合物转化成其中U是SO2的通式IX或XI的化合物，例如可以通过用3-氯过氧苯甲酸或NaIO4在存在作为催化剂的RuCl3的情况下进行氧化来进行。Substituted 4-nitroanilines of general formula IX or XI are commercially available, described in the literature or can be prepared according to methods known to those skilled in the art. s is 0 and R 2 is a substituted aryl or substituted heteroaryl as defined above such as furyl, thienyl, phenyl, pyridyl, compounds of the general formula IX or XI can especially be represented by R 2 is The corresponding compound of I or Br can be obtained by crosslinking-coupling reactions known to those skilled in the art such as Suzuki coupling, Stille coupling, or other transition metal catalyzed crosslinking-coupling reactions [DWKnight, "Coupling reactions between sp2 carbon centers", Comprehensive OrganicSynthesis, 3rd edition, pages 481-520, Pergamon Press 1991] for preparation. Alternatively, 4-nitroanilines of general formula IX or XI can be nitrated from the corresponding 2-substituted anilines in protected or unprotected form using nitrations well known to chemists skilled in the art [R. Behnisch, "Aromatische Nitro-Verbindungen" , Methoden der Organische Chemie/(Houben-Weyl), p. 255, v.E16d, Thieme: 1992] for the preparation. This approach is particularly useful for compounds of general formula IX or XI wherein U is S, SO2 , or SO2NR11 . Compounds of formula IX or XI, wherein U is S, can also be converted into compounds of formula IX or XI, wherein U is SO , by oxidation according to methods well known to chemists in the art, for example by using 3-chloroperoxy Benzoic acid or NaIO4 is carried out by oxidation in the presence of RuCl3 as catalyst.

通式XI的化合物还可以由通式IX的化合物通过用形成R3-(Z)q-X基的适宜的亲电性试剂，非限制性地如烷基、芳基、或杂芳基氯甲酸酯或氨基甲酰氯、碳酸酐、酰基氟、酰基氯、酰基溴、酰基碘、活性酯、活性碳酸与活化试剂如碳二亚胺、磺酰氯、或异氰酸酯在适宜溶剂如乙腈、四氢呋喃、1，2-二氯乙烷、或二氯甲烷中，在通过常规加热或在微薄辐射下获得的适宜的温度如室温或回流下，在加入或不加入碱如氧化镁、碳酸钾、氢化钠、三烷基胺、纯化钠-或钾、碳酸钠或钾、碳酸氢钠或钾、或吡啶的情况下进行的反应，一些本领域化学人员中众所周知的反应来进行制备的。Compounds of general formula XI can also be synthesized from compounds of general formula IX by using suitable electrophilic reagents that form R 3 -(Z) q -X groups, such as, without limitation, alkyl, aryl, or heteroaryl chlorides Formic acid ester or carbamoyl chloride, carbonic anhydride, acid fluoride, acid chloride, acid bromide, acid iodide, active ester, active carbonic acid and an activation reagent such as carbodiimide, sulfuryl chloride, or isocyanate in a suitable solvent such as acetonitrile, tetrahydrofuran, In 1,2-dichloroethane or dichloromethane, at a suitable temperature such as room temperature or reflux obtained by conventional heating or under micro-irradiation, with or without adding alkali such as magnesium oxide, potassium carbonate, sodium hydride , trialkylamine, purified sodium- or potassium, sodium or potassium carbonate, sodium or potassium bicarbonate, or pyridine, some reactions well known to chemists in the art.

另外，对于R2的另外的变型而言，可以用本领域化学人员公知的方法将其中R2是甲基、U是氧、和s是1的通式XI的化合物脱甲基，如用三溴化硼在适宜的溶剂如二氯甲烷中在适宜的温度如0℃或室温下进行对其进行处理来脱甲基。然后，用本领域化学人员公知的方法将所得的苯酚转化成其中U是氧和s是1的通式XI的化合物。该类方法包括：(a)将亲电试剂，如烷基氯、烷基溴、烷基碘、苄基氯、碳酸氯、碳酸溴、或碳酸酐在存在适宜的碱如碳酸钾的情况下在适宜的溶剂如四氢呋喃、N，N-二甲基甲酰胺、或1，2二氯乙烷中在适宜的温度如室温或回流温度下进行反应；(b)将烷基、苄基、或杂芳基烷基醇在被称为Mitsunobu反应的条件下进行反应(O.MitsunobuSynthesis 1981，1)。In addition, for additional variants of R2 , compounds of general formula XI wherein R2 is methyl, U is oxygen, and s is 1 can be demethylated using methods known to chemists in the art, such as with tris Boron bromide is demethylated by treating it in a suitable solvent such as dichloromethane at a suitable temperature such as 0°C or room temperature. The resulting phenols are then converted to compounds of general formula XI wherein U is oxygen and s is 1 by methods well known to chemists skilled in the art. Such methods include: (a) reacting an electrophile such as an alkyl chloride, bromide, iodide, benzyl chloride, chlorine carbonate, bromide carbonate, or carbonic anhydride in the presence of a suitable base such as potassium carbonate In a suitable solvent such as tetrahydrofuran, N,N-dimethylformamide, or 1,2 dichloroethane, the reaction is carried out at a suitable temperature such as room temperature or reflux temperature; (b) alkyl, benzyl, or Heteroarylalkyl alcohols are reacted under conditions known as the Mitsunobu reaction (O. Mitsunobu Synthesis 1981, 1).

可以用适宜的还原剂如存在酸如醋酸或水性盐酸情况下的锌或铁粉、或存在适宜氢化催化剂如钯披活性碳的情况下的氢气或甲酸铵在适宜的溶剂如甲醇、乙醇、或四氢呋喃中在适宜的温度下或在超声辐射下对通式XI的化合物中的硝基进行还原，从而得到通式XII的苯胺。或者，可以在本领域化学人员众所周知的条件下用氯化锡(II)或连二亚硫酸钠作为还原剂。A suitable reducing agent such as zinc or iron powder in the presence of an acid such as acetic acid or aqueous hydrochloric acid, or hydrogen or ammonium formate in the presence of a suitable hydrogenation catalyst such as palladium on activated carbon in a suitable solvent such as methanol, ethanol, or The nitro group in the compound of general formula XI is reduced in tetrahydrofuran at a suitable temperature or under ultrasonic irradiation to obtain aniline of general formula XII. Alternatively, tin(II) chloride or sodium dithionite can be used as reducing agent under conditions well known to chemists skilled in the art.

用其中Y的定义如上所述的通式YCHO的醛在适宜的溶剂如甲醇、乙醇、二甲苯、四氢呋喃、乙腈、或其混合物中在适宜的温度下对所获得的通式XII的苯胺进行本领域化学人员公知的还原性烷基化反应，形成亚胺中间体，将其原位还原或者通过蒸发溶剂或结晶将其分离出来。用还原剂如硼氢化钠(sodium borohydrate)或氰基硼氢化钠(sodium cyanoborohydrate)在适宜的溶剂如乙醇、甲醇或乙腈中在加入或不加入催化数量的酸如醋酸的情况下在适宜的温度下将其还原成其中R1是氢的通式I的本发明的化合物。The aniline of the general formula XII obtained is subjected to the present invention at a suitable temperature with an aldehyde of the general formula YCHO wherein Y is defined as above in a suitable solvent such as methanol, ethanol, xylene, tetrahydrofuran, acetonitrile, or a mixture thereof. Reductive alkylation, well known to chemists in the art, forms an imine intermediate which is reduced in situ or isolated by evaporation of solvent or crystallization. Using a reducing agent such as sodium borohydrate (sodium borohydrate) or sodium cyanoborohydride (sodium cyanoborohydrate) in a suitable solvent such as ethanol, methanol or acetonitrile with or without the addition of a catalytic amount of acid such as acetic acid at a suitable temperature It is reduced to compounds of the invention of the general formula I wherein R 1 is hydrogen.

对于R1的变型而言，可以通过用适宜的醛和还原剂如上述的氰基硼氢化钠进行的第二次还原性烷基化过程任选地对所得的其中R1是氢的通式I的化合物进行进一步衍生化。这种过程可以在用通式YCHO的醛进行第一次还原性烷基化反应后在原位进行。或者，可以通过用其中LG是适宜的离去基团如碘化物、溴化物、或磺酸酯的通式R1-LG的适宜亲电试剂在本领域化学人员公知的条件下进行的亲电性取代反应来引入R1。For the R variant, the resulting general formula wherein R is hydrogen can optionally be modified by a second reductive alkylation process with a suitable aldehyde and a reducing agent such as sodium cyanoborohydride as described above Compounds of I were further derivatized. This process can be carried out in situ after the first reductive alkylation with an aldehyde of general formula YCHO. Alternatively, the electrophilic reaction can be carried out under conditions well known to chemists in the art with a suitable electrophile of the general formula R1 -LG, wherein LG is a suitable leaving group such as iodide, bromide, or sulfonate. Sexual substitution reaction to introduce R 1 .

对于R3、Z和X另外的变型而言，通式I的本发明的化合物可以用一种供替代的选择途径获得：可以通过用适宜的保护基团(PG1)[有机合成中的保护基团(Protective Groups in Organic Synthesis)，第3版，T.W.Greene，P.G.M.Wuts，Wiley Interscience 1999]如被本领域技术人员称为TFA基团的三氟乙酰基，通过将形成保护基团的试剂如三氟醋酸酐在适宜的溶剂如1，2-二氯乙烷中在适宜的温度下进行反应而将通式IX的被取代的4-硝基苯胺中的苯胺氮保护起来来进行制备。For further variants of R 3 , Z and X, the compounds of the invention of the general formula I can be obtained by an alternative route: they can be obtained by using a suitable protecting group (PG 1 ) [protection in organic synthesis group (Protective Groups in Organic Synthesis), 3rd edition, TW Greene, PGM Wuts, Wiley Interscience 1999] such as the trifluoroacetyl group known by those skilled in the art as the TFA group, by adding a reagent that forms a protecting group such as trifluoro Acetic anhydride is prepared by protecting the aniline nitrogen in substituted 4-nitroanilines of formula IX by reacting in a suitable solvent such as 1,2-dichloroethane at a suitable temperature.

通式XIV的苯胺可以通过根据本领域技术人员公知的如上所述的硝基还原来获得。然后，用通式YCHO的醛如上所述那样对其进行还原性烷基化反应，从而得到通式XV的化合物。Anilines of general formula XIV can be obtained by reduction of the nitro group as described above according to well known to those skilled in the art. This is then reductively alkylated with an aldehyde of formula YCHO as described above to give compounds of formula XV.

将通式XV的化合物如上所述那样进行第二次还原性烷基化步骤，得到其中PG1是TFA的通式XVI的化合物。然后，可以用本领域化学人员公知的方法，如用水性碳酸钾在适宜的溶剂如甲醇中在适宜的温度下进行水解来除去该TFA基，从而得到通式XVII的化合物。Compounds of general formula XV are subjected to a second reductive alkylation step as described above to give compounds of general formula XVI wherein PG 1 is TFA. Then, the TFA group can be removed by methods known to chemists in the art, such as hydrolysis with aqueous potassium carbonate in a suitable solvent such as methanol at a suitable temperature, thereby obtaining a compound of general formula XVII.

其中R1不是氢的本发明的化合物是由通式XVII的苯胺通过用形成R3-(Z)q-X基团的适宜亲电性试剂，如烷基、芳基或杂芳基氯甲酸酯或氨基甲酰氯、酰基氯、酰基溴、酰基碘、磺酰氯、异氰酸酯、碳酸酐、活性碳酸酐与活化剂如碳二亚胺或本领域化学人员已知的其它物质在适宜的溶剂如乙腈、四氢呋喃、1，2-二氯乙烷、或二氯甲烷中在适宜的温度如室温或回流温度下在加入或不加入碱如氧化镁、碳酸钾、三烷基胺、或吡啶的情况下进行反应或者通过如上所述的其它方法来获得的。Compounds of the invention wherein R 1 is other than hydrogen are formed from anilines of general formula XVII by using a suitable electrophile forming a R 3 —(Z) q —X group, such as an alkyl, aryl or heteroaryl methyl chloride ester or carbamoyl chloride, acid chloride, acid bromide, acid iodide, sulfuryl chloride, isocyanate, carbonic anhydride, activated carbonic anhydride with an activator such as carbodiimide or other substances known to the chemist in the art in a suitable solvent such as Acetonitrile, tetrahydrofuran, 1,2-dichloroethane, or dichloromethane at a suitable temperature such as room temperature or reflux temperature with or without adding a base such as magnesium oxide, potassium carbonate, trialkylamine, or pyridine or obtained by other methods as described above.

对于其中R1是氢的通式I的本发明的化合物而言，用本领域化学人员已知的适宜的保护基团(PG2)[有机合成中的保护基团，第3版，T.W.Greene，P.G.M.Wuts，Wiley Interscience 1999]对通式XV的化合物进行保护，得到通式XVIII的化合物。其中PG2是被本领域技术人员称为Boc基团的叔-丁基羰基的通式XVIII的化合物特别是可以用形成保护基团的适宜试剂如叔-丁基碳酸酐在适宜溶剂如乙腈中和在适宜的温度下如+80℃下进行反应，从而得到其中PG2是Boc的通式XVIII的化合物来进行制备。然后，如上所述那样除去该TFA保护基(PG1)，得到通式XIX的化合物，然后，如上所述那样，用形成R3-(Z)q-X的适宜亲电试剂对其进行衍生化，得到通式XX的化合物。For compounds of the invention of formula I wherein R 1 is hydrogen, suitable protecting groups (PG 2 ) known to chemists in the art [Protecting Groups in Organic Synthesis, 3rd Edition, TW Greene, PGMWuts, Wiley Interscience 1999] protect the compound of general formula XV to obtain the compound of general formula XVIII. Compounds of general formula XVIII in which PG is tert-butylcarbonyl referred to as a Boc group by those skilled in the art can be used in particular with a suitable reagent forming a protecting group such as tert-butylcarbonic anhydride in a suitable solvent such as acetonitrile and react at a suitable temperature such as +80° C. to obtain a compound of general formula XVIII wherein PG 2 is Boc. Removal of the TFA protecting group (PG1) as described above then yields compounds of general formula XIX which are then derivatized with a suitable electrophile forming R3- (Z) q -X as described above , to obtain a compound of general formula XX.

或者，可以由4-硝基苯胺用如下所述的三步过程来制备通式XIX的化合物：如上所述那样将通式XXXIV的化合物还原性烷基化将得到通式XXXV的化合物，然后可以用例如重碳酸二-叔-丁酯和二甲基氨基吡啶在适宜的溶剂如四氢呋喃中对其进行保护，从而得到通式通式XXXVI的化合物，然后如上所述那样用适宜的还原剂如Na2S2O4将其还原成通式XIX的化合物。Alternatively, compounds of general formula XIX can be prepared from 4-nitroaniline in a three-step process as described below: Reductive alkylation of compounds of general formula XXXIV as described above will give compounds of general formula XXXV, which can then be Protection with, for example, di-tert-butyl bicarbonate and dimethylaminopyridine in a suitable solvent such as tetrahydrofuran affords compounds of the general formula XXXVI, which are then treated with a suitable reducing agent such as Na 2 S 2 O 4 reduces it to compounds of general formula XIX.

最后，可以用本领域化学人员公知的方法通过PG2的去保护来由通式XX的化合物获得其中R1是氢的通式I的本发明的化合物。特别是可以用本领域化学人员已知的方法如用适宜的酸例如三氟醋酸在不存在或存在溶剂如二氯甲烷或甲苯的情况下在适宜的温度下去保护来对该Boc保护基团进行裂解。Finally, the compounds of the invention of the general formula I wherein R 1 is hydrogen can be obtained from compounds of the general formula XX by deprotection of PG 2 by methods well known to chemists skilled in the art. In particular the Boc protecting group can be protected by methods known to chemists in the art such as deprotection with a suitable acid such as trifluoroacetic acid in the absence or presence of a solvent such as dichloromethane or toluene at a suitable temperature. crack.

或者，可以通过下面的途径来制备通式I的化合物：Alternatively, compounds of general formula I can be prepared via the following pathways:

其中R2、U和s的定义如上所述的通式XXI的化合物可以通过商业途径获得或者可以用本领域化学人员已知的方法来进行制备。这些方法包括5-氟-2-硝基苯酚在如上所述的用于由苯酚合成通式XI的化合物的Mitsunobu-、烷基化-或酰化条件下进行的反应。用Y-CH2-NH-R1型的胺进行的亲核芳族取代——一种本领域化学人员众所周知的反应——得到了通式XXII的化合物。或者，通式XXII的化合物可以通过如上所述的通式XXXIV的4-硝基苯胺的还原性烷基化来进行制备。通式XXIII的化合物可以通过在如上所述的用于合成通式XII化合物的条件下对硝基进行还原来进行制备。通式XXIII的化合物与如上所述的用于通式XI化合物的形成R3-(Z)q-X的适宜亲电试剂进行的反应给出了通式I的本发明的化合物。Compounds of general formula XXI wherein R 2 , U and s are as defined above are commercially available or can be prepared by methods known to chemists skilled in the art. These methods involve the reaction of 5-fluoro-2-nitrophenol under Mitsunobu-, alkylation- or acylation conditions as described above for the synthesis of compounds of general formula XI from phenol. Nucleophilic aromatic substitution with amines of the type Y- CH2 -NH- R1 - a reaction well known to chemists skilled in the art - affords compounds of general formula XXII. Alternatively, compounds of general formula XXII can be prepared by reductive alkylation of 4-nitroanilines of general formula XXXIV as described above. Compounds of general formula XXIII can be prepared by reduction of the nitro group under the conditions described above for the synthesis of compounds of general formula XII. Reaction of compounds of general formula XXIII with a suitable electrophile to form R3- (Z) q -X as described above for compounds of general formula XI gives compounds of general formula I according to the invention.

或者，s是0和R2是上面所定义的被取代的芳基或被取代的杂芳基如呋喃基、噻吩基、苯基、吡啶基的通式I的化合物可以由相应的R2是I或Br的化合物通过上述交联-偶合反应来进行制备。Alternatively, s is 0 and R 2 is a substituted aryl or substituted heteroaryl as defined above such as furyl, thienyl, phenyl, pyridyl, and the compound of formula I can be represented by the corresponding R 2 is Compounds of I or Br are prepared by the crosslinking-coupling reaction described above.

实施例Example

分析LC-MS数据(LC-MS＝LC/MS)是在配有APPI(大气压光电离)离子源和Shimadzu LC-8A/SLC-10A LC系统的PE Sciex API 150EX仪器上获得的。柱：30X4.6mm Waters Symmetry C18柱，粒度为3.5μm；溶剂系统：A＝水/三氟醋酸(100∶0.05)和B＝水/乙腈/三氟醋酸(5∶95∶0.03)；方法：在4分钟内用90％A至100％B进行线性梯度洗脱，流速为2mL/分钟。LC/MS-TOF(time-of-flight)数据是在配有Waters 2488/Sedex 754检测系统的微量(micromass)LCT 4-道MUX上获得的。柱：30X4.6mm Waters Symmetry C18柱，例如为3.5μm；溶剂系统：A＝水/三氟醋酸(100∶0.05)和B＝水/乙腈/三氟醋酸(5∶95∶0.03)；方法：在4分钟内用90％A至100％B进行线性梯度洗脱，流速为2mL/分钟。实测的分离离子值(m/z，其中m是分子离子质量和z是电荷)被指定为由最丰富的同位素组成的任选地加或减去碎片的分子量(M)。在具有[M+3]+或[M+2]+赋值的实例中，所报道的m/z值相当于从一些具有不同同位素组成的分子离子峰中选择出来的最高峰并且分子量M是以最丰富的同位素分布为基础进行计算的。通过对UV(254nm)积分和ELSD痕量来测定纯度。保留时间(RT)是以分钟为单位来进行表达的。Analytical LC-MS data (LC-MS=LC/MS) were acquired on a PE Sciex API 150EX instrument equipped with an APPI (atmospheric pressure photoionization) ion source and a Shimadzu LC-8A/SLC-10A LC system. Column: 30X4.6mm Waters Symmetry C18 column, particle size is 3.5μm; Solvent system: A=water/trifluoroacetic acid (100:0.05) and B=water/acetonitrile/trifluoroacetic acid (5:95:0.03); Method: A linear gradient from 90% A to 100% B over 4 minutes was performed at a flow rate of 2 mL/min. LC/MS-TOF (time-of-flight) data were acquired on a micromass LCT 4-channel MUX equipped with a Waters 2488/Sedex 754 detection system. Column: 30X4.6mm Waters Symmetry C18 column, such as 3.5 μm; solvent system: A=water/trifluoroacetic acid (100:0.05) and B=water/acetonitrile/trifluoroacetic acid (5:95:0.03); method: A linear gradient from 90% A to 100% B over 4 minutes was performed at a flow rate of 2 mL/min. The measured isolated ion values (m/z, where m is the molecular ion mass and z is the charge) are assigned the molecular weight (M) of optionally plus or minus the fragment composed of the most abundant isotope. In instances with [M+3] + or [M+2] + assignments, the reported m/z value corresponds to the highest peak selected from a number of molecular ion peaks with different isotopic compositions and the molecular weight M is given by The most abundant isotope distribution is the basis for calculations. Purity was determined by UV (254nm) integration and ELSD trace. Retention time (RT) is expressed in minutes.

制备LC-MS-纯化是在相同的PE Sciex API 150EX仪器上进行的。柱：50X20mm YMC ODS-A，粒度为5μm；方法：在7分钟内用80％A至100％B进行线性梯度洗脱，流速为22.7mL/分钟。用分流MS检测来进行分级收集。Preparative LC-MS-purification was performed on the same PE Sciex API 150EX instrument. Column: 50X20mm YMC ODS-A, particle size 5μm; method: linear gradient elution with 80% A to 100% B within 7 minutes, the flow rate is 22.7mL/min. Fractional collection was performed with split flow MS detection.

1H NMR谱是在500.13MHz或250.13MHz下进行记录的，其是分别在Bruker Avance DRX500或Bruker AC 250仪器上进行记录的。用氘化氯仿(99.8％D)或二甲基亚砜(99.8％D)作为溶剂。用TMS作为内部参照标准。化学位移值是以ppm-值为单位进行表示的。用下面的缩写来对NMR信号的多重性进行表示：s＝单峰，d＝双峰，t＝三重峰，q＝四重峰，qui＝五重峰，h＝六重峰，dd＝双双峰，dt＝双三重峰，dq＝双四重峰，tt＝三三重峰，m＝多重峰和br.s＝宽单峰，br.d＝宽双峰，br.t＝宽三重峰。 1 H NMR spectra were recorded at 500.13 MHz or 250.13 MHz on a Bruker Avance DRX500 or Bruker AC 250 instrument, respectively. Deuterated chloroform (99.8% D) or dimethylsulfoxide (99.8% D) was used as solvent. TMS was used as an internal reference standard. Chemical shift values are expressed in ppm-value units. The following abbreviations are used to indicate the multiplicity of NMR signals: s = singlet, d = doublet, t = triplet, q = quartet, qui = quintet, h = sextet, dd = doublet doublet, dt = double triplet, dq = double quartet, tt = triplet triplet, m = multiplet and br.s = broad singlet, br.d = broad doublet, br.t = broad triplet peak.

中间体的制备Preparation of intermediates

N-(对-氟苄基)-甲基胺是根据G.M.Singer和A.W.AndrewsJ.Med.Chem.1983，26，309所述的方法来进行合成的。2-碘-4-硝基苯胺是根据J.J.Pak，T.J.R.Weakly，和M.MHaley J.Amer.Chem.Soc.19999121，8182所述的方法来进行制备的。N-(p-fluorobenzyl)-methylamine was synthesized according to the method described by G.M. Singer and A.W. Andrews J. Med. Chem. 1983, 26, 309. 2-Iodo-4-nitroaniline was prepared according to the method described by J.J. Pak, T.J.R. Weakly, and M.M Haley J.Amer.Chem.Soc.19999121,8182.

通式XI的中间体的制备Preparation of Intermediates of General Formula XI

(2-氯-4-硝基苯基)-氨基甲酸乙酯.(2-Chloro-4-nitrophenyl)-carbamate ethyl ester.

将MgO(2.0g)、2-氯-4-硝基苯胺(3.768g，21.83mmol)和氯甲酸乙酯(5mL)在乙腈(25mL)中的混悬液加热至回流温度加热4小时，然后加入更多的氯甲酸乙酯(4mL)。继续加热至完全转化(20小时)，然后将该反应混合物用SiO2塞子过滤，用乙酸乙酯作为洗脱剂。真空蒸发(50℃)，得到5.8g(收率为100％)标题化合物粗品，将其不进行进一步纯化地用于下一步。LC/MS(m/z)245([M+H]+)；RT＝2.95，(UV，ELSD)96％，98.5％。1H NMR(DMSO-d6)：1.27(t，3H)，4.19(q，2H)，8.06(d，1H)，8.19(dd，1H)，8.30(d，1H)，9.49(s，NH)。A suspension of MgO (2.0 g), 2-chloro-4-nitroaniline (3.768 g, 21.83 mmol) and ethyl chloroformate (5 mL) in acetonitrile (25 mL) was heated to reflux temperature for 4 h, then More ethyl chloroformate (4 mL) was added. Heating was continued until complete conversion (20 h), then the reaction mixture was filtered through a plug of SiO2 using ethyl acetate as eluent. Evaporation in vacuo (50° C.) gave 5.8 g (100% yield) of the crude title compound, which was used in the next step without further purification. LC/MS (m/z) 245 ([M+H] + ); RT = 2.95, (UV, ELSD) 96%, 98.5%. 1 H NMR (DMSO-d 6 ): 1.27(t, 3H), 4.19(q, 2H), 8.06(d, 1H), 8.19(dd, 1H), 8.30(d, 1H), 9.49(s, NH ).

类似地用适宜的氯甲酸酯来制备下面的化合物：The following compounds were prepared similarly using the appropriate chloroformate:

(2-氯-4-硝基苯基)-氨基甲酸丙酯。(2-Chloro-4-nitrophenyl)-propyl carbamate.

代替性使用氯甲酸丙酯和四氢呋喃。通过向该粗品中加入丙醚使标题化合物结晶并通过过滤将其分离。收率为3.3g(62％)，无色固体NMR(DMSO-d6)：0.94(t，3H)，1.67(m，2H)，4.10(t，2H)，8.06(d，1H)，8.20(dd，1H)，8.31(d，1H)，9.52(s，NH)。Propyl chloroformate and tetrahydrofuran were used instead. The title compound was crystallized by adding propyl ether to the crude and isolated by filtration. Yield 3.3 g (62%), colorless solid NMR (DMSO-d 6 ): 0.94 (t, 3H), 1.67 (m, 2H), 4.10 (t, 2H), 8.06 (d, 1H), 8.20 (dd, 1H), 8.31 (d, 1H), 9.52 (s, NH).

(4-硝基苯基)-氨基甲酸丙酯。(4-Nitrophenyl)-propyl carbamate.

在室温下，在作为溶剂的丙酮中进行反应。将该产物不进行纯化地用于下一步。The reaction was carried out in acetone as solvent at room temperature. The product was used in the next step without purification.

(4-硝基苯基)-氨基甲酸乙酯。(4-Nitrophenyl)-urethane ethyl ester.

在室温下，在作为溶剂的丙酮中进行反应。将该产物不进行纯化地用于下一步。The reaction was carried out in acetone as solvent at room temperature. The product was used in the next step without purification.

(2-甲氧基-4-硝基苯基)-氨基甲酸甲酯。(2-Methoxy-4-nitrophenyl)-methyl carbamate.

在室温下，在作为溶剂的丙酮中进行反应。将该产物不进行纯化地用于下一步。The reaction was carried out in acetone as solvent at room temperature. The product was used in the next step without purification.

(2-甲氧基-4-硝基苯基)-氨基甲酸异丙酯。(2-Methoxy-4-nitrophenyl)-carbamate isopropyl ester.

在室温下，在作为溶剂的丙酮中进行反应。将该产物不进行纯化地用于下一步。The reaction was carried out in acetone as solvent at room temperature. The product was used in the next step without purification.

(2-甲氧基-4-硝基苯基)-氨基甲酸丙酯。(2-Methoxy-4-nitrophenyl)-propyl carbamate.

在室温下，在作为溶剂的丙酮中进行反应。将该产物不进行纯化地用于下一步。The reaction was carried out in acetone as solvent at room temperature. The product was used in the next step without purification.

(2-甲氧基-4-硝基苯基)-氨基甲酸4-氟苯酯。(2-Methoxy-4-nitrophenyl)-4-fluorophenylcarbamate.

在室温下，在作为溶剂的丙酮中进行反应。将该产物不进行纯化地用于下一步。The reaction was carried out in acetone as solvent at room temperature. The product was used in the next step without purification.

(2-甲基-4-硝基苯基)-氨基甲酸乙酯。(2-Methyl-4-nitrophenyl)-carbamate ethyl ester.

将该粗品不进行进一步纯化地用于下一步。The crude product was used in the next step without further purification.

LC/MS(m/z)207.9([M-16]+)；RT＝2.69，(UV，ELSD)75％，99.7％。LC/MS (m/z) 207.9 ([M-16] + ); RT = 2.69, (UV, ELSD) 75%, 99.7%.

(2-甲基-4-硝基苯基)-氨基甲酸丙酯。(2-Methyl-4-nitrophenyl)-propyl carbamate.

将该粗品不进行进一步纯化地用于下一步。The crude product was used in the next step without further purification.

LC/MS(m/z)223.1([M-15]+)；RT＝2.97，(UV，ELSD)62％，99.7％。LC/MS (m/z) 223.1 ([M-15] + ); RT = 2.97, (UV, ELSD) 62%, 99.7%.

(2-溴-4-硝基苯基)-氨基甲酸丙酯。(2-Bromo-4-nitrophenyl)-propyl carbamate.

将该粗品用乙酸乙酯-己烷结晶。1H NMR(DMSO-d6)：0.94(t，3H)，1.66(m，2H)，4.10(t，2H)，7.97(d，1H)，8.23(dd，1H)，8.44(d，1H)，9.28(br.s，NH)。The crude product was crystallized from ethyl acetate-hexane. 1 H NMR (DMSO-d 6 ): 0.94(t, 3H), 1.66(m, 2H), 4.10(t, 2H), 7.97(d, 1H), 8.23(dd, 1H), 8.44(d, 1H ), 9.28 (br.s, NH).

(2-碘-4-硝基苯基)-氨基甲酸丙酯。(2-iodo-4-nitrophenyl)-propyl carbamate.

通过用乙酸乙酯-己烷进行结晶来对该粗品进行纯化。浅黄色针状物。1H NMR(DMSO-d6)：0.94(t，3H)，1.66(m，2H)，4.09(t，2H)，7.79(d，1H)，8.24(dd，1H)，8.60(d，1H)，9.07(br.s，NH)。LC/MS(m/z)335.0([M-O]+)；RT＝3.40，(UV，ELSD)99％，100％。The crude product was purified by crystallization from ethyl acetate-hexane. Pale yellow needles. 1 H NMR (DMSO-d 6 ): 0.94(t, 3H), 1.66(m, 2H), 4.09(t, 2H), 7.79(d, 1H), 8.24(dd, 1H), 8.60(d, 1H ), 9.07 (br.s, NH). LC/MS (m/z) 335.0 ([MO] + ); RT = 3.40, (UV, ELSD) 99%, 100%.

(4-硝基-2-氰基苯基)-氨基甲酸丙酯。(4-Nitro-2-cyanophenyl)-propyl carbamate.

替代性地使用氢化钠作为碱，然后在室温下加入氯甲酸丙酯。用饱和水性碳酸氢钠(NaHCO3)在甲醇中将该被双酰化产物污染的粗品处理16小时并用闪柱色谱纯化。1H NMR(CDCl3)：1.01(t，3H)，1.76(m，2H)，4.22(t，2H)，7.47(br.s，1H，NH)，8.43(dd，1H)，8.47(d，1H)，8.57(d，1H)。Alternatively sodium hydride was used as base followed by addition of propyl chloroformate at room temperature. The bisacylated crude product was treated with saturated aqueous sodium bicarbonate ( NaHCO3 ) in methanol for 16 hours and purified by flash column chromatography. 1 H NMR (CDCl 3 ): 1.01(t, 3H), 1.76(m, 2H), 4.22(t, 2H), 7.47(br.s, 1H, NH), 8.43(dd, 1H), 8.47(d , 1H), 8.57(d, 1H).

相似地制备下面的化合物：The following compounds were similarly prepared:

(4-硝基-2-氰基苯基)-氨基甲酸乙酯。(4-Nitro-2-cyanophenyl)-urethane ethyl ester.

1H NMR(DMSO-d6)：1.28(t，3H)，4.21(q，2H)，7.88(d，1H)，8.47(dd，1H)，8.68(d，1H)，10.34(s，1H，NH)。LC/MS(m/z)220.1([M+H]+)，RT＝2.46，(UV，ELSD)97％，98％。 1 H NMR (DMSO-d 6 ): 1.28(t, 3H), 4.21(q, 2H), 7.88(d, 1H), 8.47(dd, 1H), 8.68(d, 1H), 10.34(s, 1H , NH). LC/MS (m/z) 220.1 ([M+H] + ), RT = 2.46, (UV, ELSD) 97%, 98%.

(2-三氟甲基-4-硝基苯基)-氨基甲酸丙酯。(2-Trifluoromethyl-4-nitrophenyl)-propyl carbamate.

1H NMR(CDCl3)：1.00(t，3H)，1.75(m，2H)，4.20(t，2H)，7.26(br.s，1H，NH)，8.41(dd，1H)，8.50(d，1H)，8.57(d，1H)。 1 H NMR (CDCl 3 ): 1.00(t, 3H), 1.75(m, 2H), 4.20(t, 2H), 7.26(br.s, 1H, NH), 8.41(dd, 1H), 8.50(d , 1H), 8.57(d, 1H).

(2-三氟甲基-4-硝基苯基)-氨基甲酸乙酯。(2-Trifluoromethyl-4-nitrophenyl)-carbamate ethyl ester.

1H NMR(CDCl3)：1.37(t，3H)，4.31(q，2H)，7.25(br.s，1H，NH)，8.41(dd，1H)，8.50(d，1H)，8.57(d，1H)。 1 H NMR (CDCl 3 ): 1.37(t, 3H), 4.31(q, 2H), 7.25(br.s, 1H, NH), 8.41(dd, 1H), 8.50(d, 1H), 8.57(d , 1H).

N-(2-甲氧基-4-硝基苯基)-丁酰胺。N-(2-Methoxy-4-nitrophenyl)-butyramide.

向冰冷的(冰/水浴)2-甲氧基-4-硝基苯胺(4.00g，23.8mmol)在乙腈(40mL)和三乙胺(5mL)中的溶液中加入丁酰氯(2.66g，25mmol)。在30分钟后，将得到的混悬液倾倒到饱和碳酸氢钠(NaHCO3)水溶液(300mL)中。在将其声处理10分钟后，通过过滤分离出黄褐色固体形式的标题化合物，用水洗涤并将其真空干燥。收率为5.34g，94％。LC/MS(m/z)238.9([M+H]+)；RT＝2.69，(UV，ELSD)98％，99％。1HNMR(DMSO-d6)：0.91(t，3H)，1.60(m，2H)，2.47(t，2H)，3.98(s，3H，OMe)，7.79(s，1H)，7.88(dd，1H)，8.39(d，1H)，9.50(s，1H，NH)。To an ice-cold (ice/water bath) solution of 2-methoxy-4-nitroaniline (4.00 g, 23.8 mmol) in acetonitrile (40 mL) and triethylamine (5 mL) was added butyryl chloride (2.66 g, 25 mmol ). After 30 minutes, the resulting suspension was poured into saturated aqueous sodium bicarbonate (NaHCO 3 ) solution (300 mL). After it was sonicated for 10 minutes, the title compound was isolated by filtration as a tan solid, washed with water and dried in vacuo. Yield 5.34g, 94%. LC/MS (m/z) 238.9 ([M+H] + ); RT = 2.69, (UV, ELSD) 98%, 99%. 1 HNMR (DMSO-d 6 ): 0.91(t, 3H), 1.60(m, 2H), 2.47(t, 2H), 3.98(s, 3H, OMe), 7.79(s, 1H), 7.88(dd, 1H), 8.39 (d, 1H), 9.50 (s, 1H, NH).

用适宜的酰基氯相似地制备下面的化合物：The following compounds were similarly prepared using the appropriate acid chloride:

N-(2-甲氧基-4-硝基苯基)-3，4-二氯苯甲酰胺。N-(2-methoxy-4-nitrophenyl)-3,4-dichlorobenzamide.

LC/MS(m/z)313.0([M+H-NO]+；RT＝3.72，(UV，ELSD)99％，100％。LC/MS (m/z) 313.0 ([M+H-NO] + ; RT = 3.72, (UV, ELSD) 99%, 100%.

1H NMR(DMSO-d6)：4.0(s，3H，OMe)，7.82(d，1H)，7.88(d，11I)，7.93(m，2H)，8.17(d，1H)，8.20(s，1H)，10.01(s，1H，NH)。 1 H NMR (DMSO-d 6 ): 4.0(s, 3H, OMe), 7.82(d, 1H), 7.88(d, 11I), 7.93(m, 2H), 8.17(d, 1H), 8.20(s , 1H), 10.01 (s, 1H, NH).

3，3-二甲基-N-(-n2乙基-4-硝基苯基)-丁酰胺。3,3-Dimethyl-N-(-n2ethyl-4-nitrophenyl)-butanamide.

向2-甲基-4-硝基苯胺(5g，32.9mmol)在乙腈(75mL)中的溶液中加入叔-丁基乙酰氯(5.3g，1.2当量)。将所得的混合物分配到15Smith Process小瓶中并将其密封。将各小瓶加热并将其在微波辐射下在150℃下搅拌10分钟。将所合并到混合物真空蒸发，得到9.27g固体(100％)，将其不进行进一步纯化地用于下一步。To a solution of 2-methyl-4-nitroaniline (5 g, 32.9 mmol) in acetonitrile (75 mL) was added tert-butylacetyl chloride (5.3 g, 1.2 equiv). The resulting mixture was dispensed into 15Smith Process vials and sealed. Each vial was heated and stirred at 150°C for 10 minutes under microwave irradiation. The combined mixture was evaporated in vacuo to give 9.27 g of solid (100%) which was used in the next step without further purification.

LC/MS(m/z)251.1([M+H]+)；RT＝3.01，(UV，ELSD)89％，99.6％。1HNMR(DMSO-d6)：1.05(s，9H)，2.33(s，2H)，2.36(s，3H)，7.91(d，1H)，8.05(dd，1H)，8.12(d，1H)，9.41(s，1H，NH)。LC/MS (m/z) 251.1 ([M+H] + ); RT = 3.01, (UV, ELSD) 89%, 99.6%. 1 HNMR (DMSO-d 6 ): 1.05(s, 9H), 2.33(s, 2H), 2.36(s, 3H), 7.91(d, 1H), 8.05(dd, 1H), 8.12(d, 1H) , 9.41 (s, 1H, NH).

已经相似地制备了下面的化合物：The following compounds have been prepared similarly:

2，2-二甲基-N-(2-甲基-4-硝基苯基)-丙酰胺。2,2-Dimethyl-N-(2-methyl-4-nitrophenyl)-propionamide.

LC/MS(m/z)237.1([M+H]+)；RT＝2.72，(UV，ELSD)96.7％，98.6％。1H NMR(DMSO-d6)：1.26(s，9H)，2.31(s，3H)，7.61(d，1H)，8.05(dd，1H)，8.14(d，1H)，9.06(s，1H，NH)。LC/MS (m/z) 237.1 ([M+H] + ); RT = 2.72, (UV, ELSD) 96.7%, 98.6%. 1 H NMR (DMSO-d 6 ): 1.26(s, 9H), 2.31(s, 3H), 7.61(d, 1H), 8.05(dd, 1H), 8.14(d, 1H), 9.06(s, 1H , NH).

2-(4-氟苯基)-N-(2-甲基-4-硝基苯基)-乙酰胺。2-(4-fluorophenyl)-N-(2-methyl-4-nitrophenyl)-acetamide.

LC/MS(m/z)288.9([M+H]+)；RT＝2.90，(UV，ELSD)99.6％，99.4％。1H NMR(DMSO-d6)：2.34(s，3H)，3.79(s，2H)，7.18(t，2H)，7.39(dd，2H)，7.91(d，1H)，8.06(dd，1H)，8.13(d，1H)，9.72(s，1H，NH)。LC/MS (m/z) 288.9 ([M+H] + ); RT = 2.90, (UV, ELSD) 99.6%, 99.4%. 1 H NMR (DMSO-d 6 ): 2.34(s, 3H), 3.79(s, 2H), 7.18(t, 2H), 7.39(dd, 2H), 7.91(d, 1H), 8.06(dd, 1H ), 8.13 (d, 1H), 9.72 (s, 1H, NH).

2-(4-氟苯基)-N-(2-碘4-硝基苯基)-乙酰胺。2-(4-fluorophenyl)-N-(2-iodo4-nitrophenyl)-acetamide.

用冰冷的乙腈对该产物进行洗涤。1H NMR(DMSO-d6)：3.81(s，2H)，7.16-7.19(m，2H)，7.41-7.44(m，2H)，7.87(d，1H)，8.23(dd，1H)，8.62(d，1H)，9.66(bs，1H)。The product was washed with ice-cold acetonitrile. 1 H NMR (DMSO-d 6 ): 3.81 (s, 2H), 7.16-7.19 (m, 2H), 7.41-7.44 (m, 2H), 7.87 (d, 1H), 8.23 (dd, 1H), 8.62 (d, 1H), 9.66 (bs, 1H).

(2-碘-4-硝基苯基)-氨基甲酸乙酯。(2-iodo-4-nitrophenyl)-urethane ethyl ester.

用闪柱色谱对该产物进行纯化(二氧化硅，庚烷/乙酸乙酯)。1HNMR(DMSO-d6)：1.27(t，3H)，4.18(q，2H)，7.80(d，1H)，8.24(dd，1H)，8.60(d，1H)，9.05(s，1H)。The product was purified by flash column chromatography (silica, heptane/ethyl acetate). 1 HNMR (DMSO-d 6 ): 1.27(t, 3H), 4.18(q, 2H), 7.80(d, 1H), 8.24(dd, 1H), 8.60(d, 1H), 9.05(s, 1H) .

(2-(呋喃-2-基)-4-硝基苯基)-氨基甲酸丙酯。(2-(furan-2-yl)-4-nitrophenyl)-carbamate propyl ester.

将(2-碘-4-硝基苯基)-氨基甲酸丙酯(30mg，0.086mmol)、0.9M碳酸钾(K2CO3)水溶液(0.285mL，0.257mmol)、醋酸钯(II)(5mg)和2-呋喃硼酸(48mg，0.428mmol)在丙酮(2mL)中的混合物在该密封的小瓶中在微波辐射下加热至+125℃加热3分钟。将所得的反应混合物蒸发并将标题化合物用SiO2闪柱色谱纯化(5g，庚烷-乙酸乙酯梯度洗脱)。收率为21mg，84％。1H NMR(CDCl3)：1.00(t，3H)，1.75(m，2H)，4.18(t，2H)，6.62(dd，1H，呋喃)，6.79(d，1H，呋喃)，7.64(d，1H，呋喃)，8.16(dd，1H)，8.36(br.s，1H，NH)，8.39(d，1H)，8.48(d，1H)。LC/MS(m/z)261.0([M+H]+)；RT＝1.57。(2-Iodo-4-nitrophenyl)-propyl carbamate (30 mg, 0.086 mmol), 0.9M aqueous potassium carbonate (K 2 CO 3 ) solution (0.285 mL, 0.257 mmol), palladium(II) acetate ( 5 mg) and 2-furanboronic acid (48 mg, 0.428 mmol) in acetone (2 mL) was heated in the sealed vial to +125° C. for 3 minutes under microwave irradiation. The resulting reaction mixture was evaporated and the title compound was purified by flash chromatography on SiO2 (5 g, heptane-ethyl acetate gradient). Yield 21 mg, 84%. 1 H NMR (CDCl 3 ): 1.00(t, 3H), 1.75(m, 2H), 4.18(t, 2H), 6.62(dd, 1H, furan), 6.79(d, 1H, furan), 7.64(d , 1H, furan), 8.16 (dd, 1H), 8.36 (br.s, 1H, NH), 8.39 (d, 1H), 8.48 (d, 1H). LC/MS (m/z) 261.0 ([M+H] + ); RT = 1.57.

用适宜的硼酸类似地制备下面的化合物：The following compounds were prepared analogously using the appropriate boronic acid:

(2-苯基-4-硝基苯基)-氨基甲酸丙酯。(2-Phenyl-4-nitrophenyl)-propyl carbamate.

将该混合物不进行纯化地用于下一步。The mixture was used in the next step without purification.

(2-甲氧基-4-硝基苯基)-氨基甲酸乙酯(2-Methoxy-4-nitrophenyl)-ethyl carbamate

将2-甲氧基-4-硝基苯基胺(5.0g)溶解于无水二噁烷(30mL)中并在0℃下向其中加入N，N-二异丙基乙基胺(7.8mL)。向其中滴加位于二噁烷(35mL)中的氯甲酸乙酯(4.25mL)，并使所得的混合物加温至室温并将其搅拌一整夜。向其中加入水(200mL)并将该混合物用乙酸乙酯(3×150mL)进行萃取。将所合并得有机相用水(2×200mL)和盐水(200mL)进行洗涤，用硫酸钠进行干燥，过滤，并将其真空蒸发。将该粗品用乙醇重结晶，得到无色固体形式的标题化合物(4.45g，62％)。2-Methoxy-4-nitrophenylamine (5.0 g) was dissolved in anhydrous dioxane (30 mL) and N, N-diisopropylethylamine (7.8 mL). Ethyl chloroformate (4.25 mL) in dioxane (35 mL) was added dropwise, and the resulting mixture was allowed to warm to room temperature and stirred overnight. Water (200 mL) was added and the mixture was extracted with ethyl acetate (3 x 150 mL). The combined organic phases were washed with water (2 x 200 mL) and brine (200 mL), dried over sodium sulfate, filtered and evaporated in vacuo. The crude product was recrystallized from ethanol to give the title compound (4.45 g, 62%) as a colorless solid.

1H NMR(DMSO-d6)：1.26(t，3H)，3.94(s，3H)，4.18(q，2H)，7.78(d，1H)，7.90(dd，1H)，8.09(d，1H)，8.99(s，1H)。 1 H NMR (DMSO-d 6 ): 1.26(t, 3H), 3.94(s, 3H), 4.18(q, 2H), 7.78(d, 1H), 7.90(dd, 1H), 8.09(d, 1H ), 8.99(s, 1H).

(2-羟基-4-硝基苯基)-氨基甲酸乙酯(2-Hydroxy-4-nitrophenyl)-urethane

将(2-甲氧基-4-硝基苯基)-氨基甲酸乙酯(2.15g)分散于1，2-二氯乙烷(20mL)中并将其冷却至0℃。向其中滴加位于1，2-二氯乙烷(10mL)中的三溴化硼(2.0mL)。将该反应混合物在0℃下搅拌10分钟和在室温下搅拌30分钟。将该混合物再冷却至0℃，并小心地向其中加入水(10mL)。将该反应混合物用饱和碳酸氢钠水溶液和水性盐酸(5M)中和。将所得的混合物用乙酸乙酯(3×100mL)萃取。将所合并的有机相用水(2×100mL)和盐水(100mL)洗涤，用硫酸镁干燥，过滤，并将其真空蒸发，得到褐色固体形式的标题化合物(1.96g，97％)。Ethyl (2-methoxy-4-nitrophenyl)-carbamate (2.15 g) was dispersed in 1,2-dichloroethane (20 mL) and cooled to 0°C. Boron tribromide (2.0 mL) in 1,2-dichloroethane (10 mL) was added dropwise thereto. The reaction mixture was stirred at 0°C for 10 minutes and at room temperature for 30 minutes. The mixture was recooled to 0°C, and water (10 mL) was carefully added thereto. The reaction mixture was neutralized with saturated aqueous sodium bicarbonate and aqueous hydrochloric acid (5M). The resulting mixture was extracted with ethyl acetate (3 x 100 mL). The combined organic phases were washed with water (2 x 100 mL) and brine (100 mL), dried over magnesium sulfate, filtered and evaporated in vacuo to give the title compound (1.96 g, 97%) as a tan solid.

1H NM；R(DMSO-d6)：1.25(t，3H)，4.17(q，2H)，7.64(d，1H)，7.74(dd，1H)，8.01(d，1H)，8.69(s，1H)，10.96(br.s，1H)。1H NM; R(DMSO-d 6 ): 1.25(t, 3H), 4.17(q, 2H), 7.64(d, 1H), 7.74(dd, 1H), 8.01(d, 1H), 8.69(s, 1H), 10.96 (br.s, 1H).

(2-环戊氧基-4-硝基苯基)-氨基甲酸乙酯(2-Cyclopentyloxy-4-nitrophenyl)-ethyl carbamate

在氩气下，将环戊醇(7.24mL，376mM，位于无水四氢呋喃中)加入到三苯基膦(1.44g，聚苯乙烯键合，1.89mMol/g)中，然后向其中加入(2-羟基-4-硝基苯基)-氨基甲酸乙酯溶液(25.6mL，62mM，位于无水四氢呋喃中)和偶氮二甲酸二乙酯(7.24mL，376mM，位于无水四氢呋喃中)。将该反应混合物在室温下振摇一整夜。将该树脂滤出并用四氢呋喃(THF)(35mL)和甲醇(35mL)进行洗涤。将所合并的有机相真空蒸发。将该粗品用闪柱色谱纯化(硅胶，庚烷/乙酸乙酯，梯度洗脱)，得到淡黄色固体形式的标题化合物(294mg，64％)。Under argon, cyclopentanol (7.24 mL, 376 mM in anhydrous tetrahydrofuran) was added to triphenylphosphine (1.44 g, polystyrene bonded, 1.89 mMol/g) followed by (2 -Hydroxy-4-nitrophenyl)-urethane solution (25.6 mL, 62 mM in dry THF) and diethyl azodicarboxylate (7.24 mL, 376 mM in dry THF). The reaction mixture was shaken overnight at room temperature. The resin was filtered off and washed with tetrahydrofuran (THF) (35 mL) and methanol (35 mL). The combined organic phases were evaporated in vacuo. The crude product was purified by flash column chromatography (silica gel, heptane/ethyl acetate, gradient elution) to afford the title compound (294 mg, 64%) as a pale yellow solid.

1H IVMR(DMSO-d6)：1.27(t，3H)，1.59(m，2H)，1.76(m，2H)，1.87(m，2H)，1.94(m，2H)，4.19(q，2H)，5.01(h，1H)，7.72(d，1H)，7.86(dd，1H)，8.11(d，1H)，8.82(s，1H)。1H IVMR (DMSO-d 6 ): 1.27(t, 3H), 1.59(m, 2H), 1.76(m, 2H), 1.87(m, 2H), 1.94(m, 2H), 4.19(q, 2H) , 5.01 (h, 1H), 7.72 (d, 1H), 7.86 (dd, 1H), 8.11 (d, 1H), 8.82 (s, 1H).

用相似的方式制备下面的化合物：The following compounds were prepared in a similar manner:

(4-硝基-2-苯乙氧基苯基)-氨基甲酸乙酯(4-Nitro-2-phenethoxyphenyl)-ethyl carbamate

1H NMR(DMSO-d6)：1.28(t，3H)，3.15(t，2H)，4.19(q，2H)，4.38(t，2H)，7.23(t，1H)，7.32(t，2H)，7.36(d，2H)，7.80(d，1H)，7.88(dd，1H)，8.08(d，1H)，8.66(s，1H)。 1 H NMR (DMSO-d 6 ): 1.28(t, 3H), 3.15(t, 2H), 4.19(q, 2H), 4.38(t, 2H), 7.23(t, 1H), 7.32(t, 2H ), 7.36 (d, 2H), 7.80 (d, 1H), 7.88 (dd, 1H), 8.08 (d, 1H), 8.66 (s, 1H).

(2-苄氧基-4-硝基苯基)-氨基甲酸乙酯(2-Benzyloxy-4-nitrophenyl)-ethyl carbamate

1H NMR(DMSO-d6)：1.26(t，3H)，4.18(q，2H)，5.33(s，2H)，7.35(t，1H)，7.41(t，2H)，7.55(d，2H)，7.86(d，1H)，7.89(dd，1H)，8.06(d，1H)，8.95(s，1H)。 1 H NMR (DMSO-d 6 ): 1.26(t, 3H), 4.18(q, 2H), 5.33(s, 2H), 7.35(t, 1H), 7.41(t, 2H), 7.55(d, 2H ), 7.86 (d, 1H), 7.89 (dd, 1H), 8.06 (d, 1H), 8.95 (s, 1H).

(2-异丙氧基-4-硝基苯基)-氨基甲酸乙酯(2-Isopropoxy-4-nitrophenyl)-ethyl carbamate

1H NMR(DMSO-d6)：1.27(t，3H)，1.33(d，6H)，4.19(q，2H)，4.84(h，1H)，7.78(d，1H)，7.86(dd，1H)，8.12(d，1H)，8.77(s，1H)。 1 H NMR (DMSO-d 6 ): 1.27(t, 3H), 1.33(d, 6H), 4.19(q, 2H), 4.84(h, 1H), 7.78(d, 1H), 7.86(dd, 1H ), 8.12(d, 1H), 8.77(s, 1H).

通式XII的中间体的制备Preparation of Intermediates of General Formula XII

(4-氨基-2-甲氧基苯基)-氨基甲酸乙酯(4-Amino-2-methoxyphenyl)-ethyl carbamate

将(2-甲氧基-4-硝基苯基)-氨基甲酸乙酯(2.20g)溶解于乙醇(220mL)中。向其中加入水性盐酸(26mL，6M)和铁粉(4.74g)，并将该混合物在65℃下搅拌15分钟。在冷却至室温后，将该混合物用饱和碳酸氢钠水溶液中和并用乙酸乙酯(3×200mL)萃取。将该有机相用水(2×100mL)和盐水(100mL)洗涤，用硫酸镁干燥，过滤，并将其真空蒸发。将该粗品溶解于乙醇(100mL)中，并用水性盐酸(26mL，6M)和铁粉(3.7g)重复上面的方法，得到暗色油状物形式的标题化合物(1.80g，93％)。Ethyl (2-methoxy-4-nitrophenyl)-carbamate (2.20 g) was dissolved in ethanol (220 mL). Aqueous hydrochloric acid (26 mL, 6M) and iron powder (4.74 g) were added thereto, and the mixture was stirred at 65°C for 15 minutes. After cooling to room temperature, the mixture was neutralized with saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3 x 200 mL). The organic phase was washed with water (2 x 100 mL) and brine (100 mL), dried over magnesium sulfate, filtered and evaporated in vacuo. The crude product was dissolved in ethanol (100 mL), and the above procedure was repeated with aqueous hydrochloric acid (26 mL, 6M) and iron powder (3.7 g) to give the title compound (1.80 g, 93%) as a dark oil.

1H NMR(DMSO-d6)：1.19(t，3H)，3.67(s，3H)，4.01(q，2H)，4.97(s，2H)，6.08(dd，1H)，6.23(d，1H)，6.97(br.s，1H)，7.92(br.s，1H)。 1 H NMR (DMSO-d 6 ): 1.19(t, 3H), 3.67(s, 3H), 4.01(q, 2H), 4.97(s, 2H), 6.08(dd, 1H), 6.23(d, 1H ), 6.97 (br.s, 1H), 7.92 (br.s, 1H).

(4-氨基-2-碘苯基)-氨基甲酸乙酯。(4-Amino-2-iodophenyl)-urethane ethyl ester.

1H NMR(CDCl3)：1.31(t，3H)，3.58(br.s，2H)，4.21(q，2H)，6.52(br.s，1H)，6.67(dd，1H)，7.12(d，1H)，7.60(br.d，1H)。 1 H NMR (CDCl 3 ): 1.31(t, 3H), 3.58(br.s, 2H), 4.21(q, 2H), 6.52(br.s, 1H), 6.67(dd, 1H), 7.12(d , 1H), 7.60 (br.d, 1H).

相似地制备下面的化物：The following compounds were similarly prepared:

N-(4-氨基-2-碘苯基)-2-(4-氟苯基)-乙酰胺。N-(4-amino-2-iodophenyl)-2-(4-fluorophenyl)-acetamide.

1H NMR(DMSO-d6)：3.59(br.s，2H)，3.73(s，2H)，6.65(dd，1H)，7.05(d，1H)，7.09-7.12(m，3H)，7.34-7.37(m，2H)，7.82(d，1H)。 1 H NMR (DMSO-d 6 ): 3.59 (br.s, 2H), 3.73 (s, 2H), 6.65 (dd, 1H), 7.05 (d, 1H), 7.09-7.12 (m, 3H), 7.34 -7.37 (m, 2H), 7.82 (d, 1H).

(4-氨基-2-氯苯基)-氨基甲酸乙酯。(4-Amino-2-chlorophenyl)-ethylcarbamate.

向进行着强烈搅拌的冰冷的(冰/水浴)(2-氯-4-硝基苯基)-氨基甲酸乙酯(5.8g，21.8mmol)粗品在四氢呋喃(THF)(100mL)和醋酸(12mL)中的溶液中小份地加入锌粉(20g)，同时将温度维持在低于40℃的温度上。使该混合物缓慢加温至室温丙并在反应完全(1小时)后，用SiO2(20g)塞子对其进行过滤，用乙酸乙酯作为洗脱剂。将所得的溶液真空蒸发并通过用四氢呋喃(THF)/庚烷重结晶将该黄色固态的粗品残余物(4.9g)进行纯化，得到3.00g浅黄色固体形式的标题化合物，收率为56％。LC/MS(m/z)214，216(M+)；RT＝1.18，(UV，ELSD)86％，97％。1H NMR(DMSO-d6)：1.18(br.t，3H)，4.02(q，2H)，5.29(s，2H，NH2)，6.45(dd，1H)，6.61(d，1H)，6.98(br.d，1H)，8.52(br.s，NHCO)。To ice-cold (ice/water bath) crude ethyl (2-chloro-4-nitrophenyl)-carbamate (5.8 g, 21.8 mmol) in tetrahydrofuran (THF) (100 mL) and acetic acid (12 mL) under vigorous stirring ) was added in small portions to the solution in zinc dust (20 g) while maintaining the temperature below 40°C. The mixture was allowed to warm slowly to room temperature and after completion (1 h) it was filtered through a plug of SiO2 (20 g) using ethyl acetate as eluent. The resulting solution was evaporated in vacuo and the crude residue (4.9 g) as a yellow solid was purified by recrystallization from tetrahydrofuran (THF)/heptane to afford 3.00 g of the title compound as a light yellow solid in 56% yield. LC/MS (m/z) 214, 216 (M + ); RT = 1.18, (UV, ELSD) 86%, 97%. 1 H NMR (DMSO-d 6 ): 1.18 (br.t, 3H), 4.02 (q, 2H), 5.29 (s, 2H, NH 2 ), 6.45 (dd, 1H), 6.61 (d, 1H), 6.98 (br.d, 1H), 8.52 (br.s, NHCO).

相似地制备下面的化合物：The following compounds were similarly prepared:

(4氨基-2-氯苯基)-氨基甲酸丙酯。(4Amino-2-chlorophenyl)-propyl carbamate.

收率为84.6％(2.44g，无色固体)。LC/MS(m/z)228.1(M+)；RT＝1.53，(UV，ELSD)97.3％，99％。The yield was 84.6% (2.44 g, colorless solid). LC/MS (m/z) 228.1 (M + ); RT = 1.53, (UV, ELSD) 97.3%, 99%.

(4-氨基苯基)-氨基甲酸丙酯。(4-Aminophenyl)-propyl carbamate.

用SiO2闪柱色谱纯化(庚烷-乙酸乙酯梯度洗脱)。深紫色结晶固体，收率为3.066g，63.3％。LC/MS(m/z)195([M+H]+)；RT＝1.18，(UV，ELSD)87％，98.3％。Purified by flash column chromatography on SiO2 (heptane-ethyl acetate gradient). Deep purple crystalline solid, yield 3.066g, 63.3%. LC/MS (m/z) 195 ([M+H] + ); RT = 1.18, (UV, ELSD) 87%, 98.3%.

(4-氨基苯基)-氨基甲酸乙酯。(4-Aminophenyl)-urethane ethyl ester.

LC/MS(用/z)180.8([M+H]+)；RT＝0.48，(UV，ELSD)71％，97％。LC/MS (U/z) 180.8 ([M+H] + ); RT = 0.48, (UV, ELSD) 71%, 97%.

(4-氨基-2-甲氧基苯基)-氨基甲酸甲酯。(4-Amino-2-methoxyphenyl)-carbamate methyl ester.

LC/MS(m/z)197.0([M+H]+)；RT＝0.49，(UV，ELSD)71％，98％。LC/MS (m/z) 197.0 ([M+H] + ); RT = 0.49, (UV, ELSD) 71%, 98%.

(4-氨基-2-甲氧基苯基)-氨基甲酸乙酯。(4-Amino-2-methoxyphenyl)-urethane ethyl ester.

LC/MS(m/z)210.9([M+H]+)；RT＝0.98，(UV，ELSD)69％，97％。LC/MS (m/z) 210.9 ([M+H] + ); RT = 0.98, (UV, ELSD) 69%, 97%.

(4-氨基-2-甲氧基苯基)-氨基甲酸异丙酯。(4-Amino-2-methoxyphenyl)-carbamate isopropyl ester.

LC/MS(m/z)224.0(M+)；RT＝1.33，(UV，ELSD)63％，99％。LC/MS (m/z) 224.0 (M + ); RT = 1.33, (UV, ELSD) 63%, 99%.

(4-氨基-2-甲氧基苯基)-氨基甲酸丙酯。(4-Amino-2-methoxyphenyl)-propyl carbamate.

LC/MS(m/z)224.9([M+H]+)；RT＝1.36，(UV，ELSD)70％，98％。LC/MS (m/z) 224.9 ([M+H] + ); RT = 1.36, (UV, ELSD) 70%, 98%.

(4-氨基-2-甲氧基苯基)-氨基甲酸4-氟苯酯。(4-Amino-2-methoxyphenyl)-4-fluorophenylcarbamate.

LC/MS(m/z)277.0([M+H]+)；RT＝1.64，(UV，ELSD)44％，93％。LC/MS (m/z) 277.0 ([M+H] + ); RT = 1.64, (UV, ELSD) 44%, 93%.

(4-氨基-2-甲基苯基)-氨基甲酸丙酯。(4-Amino-2-methylphenyl)-propyl carbamate.

LC/MS(m/z)208.1(M+)；RT＝1.16，(UV，ELSD)95％，100％。1HNMR(CDCl3)：0.96(t，3H)，1.68(m，2H)，2.17(s，3H，Me)，3.59(br.s，2H，NH2)，4.09(t，2H)，6.14(br.s，1H，ArH)，6.51(m，2H)，7.32(br.s，1H，NH)。LC/MS (m/z) 208.1 (M + ); RT = 1.16, (UV, ELSD) 95%, 100%. 1 HNMR (CDCl 3 ): 0.96(t, 3H), 1.68(m, 2H), 2.17(s, 3H, Me), 3.59(br.s, 2H, NH 2 ), 4.09(t, 2H), 6.14 (br.s, 1H, ArH), 6.51 (m, 2H), 7.32 (br.s, 1H, NH).

(4-氨基-2-甲基苯基)-氨基甲酸乙酯。(4-Amino-2-methylphenyl)-urethane ethyl ester.

1H NMR(CDCl3)：1.28(t，3H)，2.16(s，3H，Me)，3.62(br.s，2H，NH2)，4.19(q，2H)，6.16(br.s，1H，ArH)，6.5(m，2H)，7.31(br.s，1H，NH).LC/MS(m/z)195.1([M+H]+)；RT＝0.75，(UV，ELSD)70％，95％。 1 H NMR (CDCl 3 ): 1.28(t, 3H), 2.16(s, 3H, Me), 3.62(br.s, 2H, NH 2 ), 4.19(q, 2H), 6.16(br.s, 1H , ArH), 6.5 (m, 2H), 7.31 (br.s, 1H, NH). LC/MS (m/z) 195.1 ([M+H] + ); RT=0.75, (UV, ELSD) 70 %, 95%.

(4-氨基-2-三氟甲基苯基)-氨基甲酸乙酯。(4-Amino-2-trifluoromethylphenyl)-ethyl carbamate.

1H NMR(CDCl3)：1.30(t，3H)，3.77(br.s，2H，NH2)，4.20(q，2H)，6.52(br.s，1H，ArH)，6.82(dd，1H)，6.87(unres.d，1H)，7.65(br.s，1H，NH).).LC/MS(m/z)248.1(M+)；RT＝1.65，(UV，ELSD)94％，90％。 1 H NMR (CDCl 3 ): 1.30 (t, 3H), 3.77 (br.s, 2H, NH 2 ), 4.20 (q, 2H), 6.52 (br.s, 1H, ArH), 6.82 (dd, 1H ), 6.87 (unres.d, 1H), 7.65 (br.s, 1H, NH).). LC/MS (m/z) 248.1 (M + ); RT=1.65, (UV, ELSD) 94%, 90%.

(4-氨基-2-三氟甲基苯基)-氨基甲酸丙酯。(4-Amino-2-trifluoromethylphenyl)-propyl carbamate.

1H NMR(CDCl3)：0.96(t，3H)，1.69(m，2H)，3.76(br.s，2H，NH2)，4.11(t，2H)，6.51(br.s，1H，ArH)，6.81(dd，1H)，6.87(d，1H)，7.61(br.s，1H，NH).LC/MS(m/z)261.9(M+)；RT＝2.06，(UV，ELSD)92％，98％。 1 H NMR (CDCl 3 ): 0.96(t, 3H), 1.69(m, 2H), 3.76(br.s, 2H, NH 2 ), 4.11(t, 2H), 6.51(br.s, 1H, ArH ), 6.81 (dd, 1H), 6.87 (d, 1H), 7.61 (br.s, 1H, NH). LC/MS (m/z) 261.9 (M + ); RT=2.06, (UV, ELSD) 92%, 98%.

(4-氨基-2-氰基苯基)-氨基甲酸乙酯。(4-Amino-2-cyanophenyl)-urethane ethyl ester.

1H NMR(DMSO-d6)：1.21(t，3H)，4.07(q，2H)，5.49(br.s，2H，NH2)，6.81(m，2H，ArH)，7.04(d，1H)，9.09(br.s，1H，NH)。LC/MS(m/z)204.9(M+)；RT 1.05，(UV，ELSD)98％，99％。 1 H NMR (DMSO-d 6 ): 1.21(t, 3H), 4.07(q, 2H), 5.49(br.s, 2H, NH 2 ), 6.81(m, 2H, ArH), 7.04(d, 1H ), 9.09 (br.s, 1H, NH). LC/MS (m/z) 204.9 (M + ); RT 1.05, (UV, ELSD) 98%, 99%.

(4-氨基-2-氰基苯基)-氨基甲酸丙酯。(4-Amino-2-cyanophenyl)-propyl carbamate.

1H NMR(CDCl3)：0.98(t，3H)，1.71(m，2H)，3.72(br.s，2H，NH2)，4.13(t，2H)，6.81(br.s，ArH)，6.82(d，1H)，6.89(dd，1H)，7.83(br.s，1H，NH)。LC/MS(m/z)220.1([M+H]+)；RT＝1.52，(UV，ELSD)98％，100％。 1 H NMR (CDCl 3 ): 0.98 (t, 3H), 1.71 (m, 2H), 3.72 (br.s, 2H, NH 2 ), 4.13 (t, 2H), 6.81 (br.s, ArH), 6.82 (d, 1H), 6.89 (dd, 1H), 7.83 (br.s, 1H, NH). LC/MS (m/z) 220.1 ([M+H] + ); RT = 1.52, (UV, ELSD) 98%, 100%.

N-(4-氨基-2-甲氧基苯基)-丁酰胺。N-(4-Amino-2-methoxyphenyl)-butanamide.

LC/MS(m/z)208.9([M+H]+)；RT＝0.77，(UV，ELSD)81％，95％。1HNMR(DMSO-d6)：0.89(t，3H)，1.56(m，2H)，2.22(t，2H)，3.4(十分宽的单峰，NH2)，3.69(s，3H，OMe)，6.08(dd，1H)，6.25(d，1H)，7.27(d，1H)，8.62(s，1H，NH)。LC/MS (m/z) 208.9 ([M+H] + ); RT = 0.77, (UV, ELSD) 81%, 95%. 1 HNMR (DMSO-d 6 ): 0.89 (t, 3H), 1.56 (m, 2H), 2.22 (t, 2H), 3.4 (very broad singlet, NH 2 ), 3.69 (s, 3H, OMe) , 6.08 (dd, 1H), 6.25 (d, 1H), 7.27 (d, 1H), 8.62 (s, 1H, NH).

N-(4-氨基-2-甲氧基苯基)-3，4-二氯苯甲酰胺。N-(4-amino-2-methoxyphenyl)-3,4-dichlorobenzamide.

LC/MS(m/z)311.2(M+)；RT＝1.93，(UV，ELSD)100％，100％。1HNMR(DMSO-d6)：3.70(s，3H，OMe)，5.12(br.s，2H，NH2)，6.15(dd，1H)，6.30(d，1H)，7.09(d，1H)，7.77(d，1H)，7.91(dd，1H)，8.17(d，1H)，9.46(s，1H，NH)。LC/MS (m/z) 311.2 (M + ); RT = 1.93, (UV, ELSD) 100%, 100%. 1 HNMR (DMSO-d 6 ): 3.70 (s, 3H, OMe), 5.12 (br.s, 2H, NH 2 ), 6.15 (dd, 1H), 6.30 (d, 1H), 7.09 (d, 1H) , 7.77 (d, 1H), 7.91 (dd, 1H), 8.17 (d, 1H), 9.46 (s, 1H, NH).

N-(4-氨基-2-甲基苯基)-3，3-二甲基丁酰胺.N-(4-amino-2-methylphenyl)-3,3-dimethylbutanamide.

LC/MS(m/z)221.1([M+H]+)；RT＝1.22，(UV，ELSD)53.7％，92.3％。1H NMR(DMSO-d6)：1.02(s，9H)，2.02(s，3H)，2.11(s，2H)，4.89(br.s，2H，NH2)，6.33(dd，1H)，6.38(d，1H)，6.82(d，1H)，8.83(s，1H，NH)。LC/MS (m/z) 221.1 ([M+H] + ); RT = 1.22, (UV, ELSD) 53.7%, 92.3%. 1 H NMR (DMSO-d 6 ): 1.02 (s, 9H), 2.02 (s, 3H), 2.11 (s, 2H), 4.89 (br.s, 2H, NH 2 ), 6.33 (dd, 1H), 6.38 (d, 1H), 6.82 (d, 1H), 8.83 (s, 1H, NH).

N-(4-氨基-2-甲基苯基)-2-(4-氟苯基)-乙酰胺。N-(4-amino-2-methylphenyl)-2-(4-fluorophenyl)-acetamide.

LC/MS(m/z)259.1([M+H]+)；RT＝1.36，(UV，ELSD)48.1％，91.4％。1H NMR(DMSO-d6)：1.95(s，3H)，3.56(s，2H)，4.88(br.s，2H，NH2)，6.31(dd，1H)，6.38(d，1H)，6.83(d，1H)，7.14(t，2H)，7.35(dd，2H)，9.16(s，1H，NH)。LC/MS (m/z) 259.1 ([M+H] + ); RT = 1.36, (UV, ELSD) 48.1%, 91.4%. 1 H NMR (DMSO-d 6 ): 1.95 (s, 3H), 3.56 (s, 2H), 4.88 (br.s, 2H, NH 2 ), 6.31 (dd, 1H), 6.38 (d, 1H), 6.83 (d, 1H), 7.14 (t, 2H), 7.35 (dd, 2H), 9.16 (s, 1H, NH).

N-(4-氨基-2-甲基苯基)-2，2-二甲基丙酰胺。N-(4-amino-2-methylphenyl)-2,2-dimethylpropanamide.

LC/MS(m/z)206.9([M+H]+)；RT＝0.59，(UV，ELSD)93％，95％。1HNMR(DMSO-d6)：1.19(s，9H)，1.98(s，2H)，4.87(br.s，2H，NH2)，6.33(dd，1H)，6.39(d，1H)，6.71(d，1H)，8.55(s，1H，NH)。LC/MS (m/z) 206.9 ([M+H] + ); RT = 0.59, (UV, ELSD) 93%, 95%. 1 H NMR (DMSO-d 6 ): 1.19 (s, 9H), 1.98 (s, 2H), 4.87 (br.s, 2H, NH 2 ), 6.33 (dd, 1H), 6.39 (d, 1H), 6.71 (d, 1H), 8.55 (s, 1H, NH).

[4-氨基-2-(呋喃-2-基)-苯基]-氨基甲酸丙酯。[4-Amino-2-(furan-2-yl)-phenyl]-carbamate propyl ester.

IH NMR(CDCl3)：0.96(t，3H)，1.68(m，2H)，3.65(br.s，2H，NH2)，4.10(t，2H)，6.50(dd，1H，呋喃)，6.58(d，1H，呋喃)，6.66(dd，1H)，6.91(br.s(非拆分的d)，1H)，7.26(br.s，ArH)，7.52(d，1H)，7.72(br.s，1H，NH).LC/MS(m/z)261.0([M+H]+)；RT＝1.57。IH NMR (CDCl 3 ): 0.96(t, 3H), 1.68(m, 2H), 3.65(br.s, 2H, NH 2 ), 4.10(t, 2H), 6.50(dd, 1H, furan), 6.58 (d, 1H, furan), 6.66 (dd, 1H), 6.91 (br.s (non-resolved d), 1H), 7.26 (br.s, ArH), 7.52 (d, 1H), 7.72 (br .s, 1H, NH). LC/MS (m/z) 261.0 ([M+H] + ); RT = 1.57.

(2-苯基-4-氨基苯基)-氨基甲酸丙酯。(2-Phenyl-4-aminophenyl)-propyl carbamate.

LC/MS(m/z)271.1([M+H]+)；RT＝1.75，(UV，ELSD)57％，99％。LC/MS (m/z) 271.1 ([M+H] + ); RT = 1.75, (UV, ELSD) 57%, 99%.

(4-氨基-2-溴苯基)-氨基甲酸丙酯。(4-Amino-2-bromophenyl)-propyl carbamate.

将铁粉(20g，过量)和(2-溴-4-硝基苯基)-氨基甲酸丙酯(2.183g，7.20mmol)在乙醇(80mL)和6M水性盐酸(20mL)中的混悬液在室温下声处理10分钟。将该混合物缓慢倾倒到饱和碳酸氢钠(NaHCO3)水溶液中，过滤并用乙酸乙酯对其进行萃取。将所合并得有机溶液用包含NaHCO3洗涤3次，用硫酸钠(Na2SO4)进行干燥并将其真空蒸发，得到1.67g浅黄色油状物形式的标题化合物，将其固化。收率为85％。LC/MS(m/z)271.9，273.8(M+)；RT＝1.30，(UV，ELSD)99％，100％。1HNMR(DMSO-d6)：0.90(br.s(未拆分的t)，3H)，1.59(br.s(未拆分的m)，2H)，3.94(t，2H)，5.31(s，2H，NH2)，6.50(dd，1H)，6.80(未拆分的d，1H)，6.96(br.d，1H)，8.51(br.s，NHCO)。A suspension of iron powder (20 g, excess) and (2-bromo-4-nitrophenyl)-propyl carbamate (2.183 g, 7.20 mmol) in ethanol (80 mL) and 6M aqueous hydrochloric acid (20 mL) Sonicate for 10 min at room temperature. The mixture was poured slowly into saturated aqueous sodium bicarbonate (NaHCO 3 ), filtered and extracted with ethyl acetate. The combined organic solutions were washed 3 times with NaHCO3 , dried over sodium sulfate ( Na2SO4 ) and evaporated in vacuo to afford 1.67 g of the title compound as a light yellow oil which solidified. The yield was 85%. LC/MS (m/z) 271.9, 273.8 (M + ); RT = 1.30, (UV, ELSD) 99%, 100%. 1 H NMR (DMSO-d 6 ): 0.90 (br.s (unresolved t), 3H), 1.59 (br.s (unresolved m), 2H), 3.94 (t, 2H), 5.31 ( s, 2H, NH2 ), 6.50 (dd, 1H), 6.80 (unresolved d, 1H), 6.96 (br.d, 1H), 8.51 (br.s, NHCO).

类似地制备下面的化合物：The following compounds were prepared analogously:

(4-氨基-2-碘苯基)-氨基甲酸丙酯。(4-Amino-2-iodophenyl)-propyl carbamate.

1H NMR(CDCl3)：0.97(t，3H)，1.69(m，2H)，3.59(br.s，2H，NH2)，4.11(t，2H)，6.53(br.s，1H，ArH)，6.66(dd，1H)，7.11(d，1H)，7.61(br.s，1H，NH)。LC/MS(m/z)320.7([M+H]+)；RT＝1.71，(UV，ELSD)98％，99％。 1 H NMR (CDCl 3 ): 0.97(t, 3H), 1.69(m, 2H), 3.59(br.s, 2H, NH 2 ), 4.11(t, 2H), 6.53(br.s, 1H, ArH ), 6.66 (dd, 1H), 7.11 (d, 1H), 7.61 (br.s, 1H, NH). LC/MS (m/z) 320.7 ([M+H] + ); RT = 1.71, (UV, ELSD) 98%, 99%.

通式XIII-XXIII的中间体的合成：Synthesis of intermediates of general formula XIII-XXIII:

N-(4-氨基-2-氯苯基)-2，2，2-三氟乙酰胺。N-(4-amino-2-chlorophenyl)-2,2,2-trifluoroacetamide.

向4-硝基-2-氯苯胺(17.2g，0.1mol)在1，2-二氯乙烷(100mL)中的混悬液中加入三氟醋酸酐(16mL，0.113mol)。在5分钟后，将得到的黄色溶液真空蒸发。如上所述那样，将所得的黄色的N-(4-硝基-2-氯苯基)-2，2，2-三氟乙酰胺固体用Zn-粉在四氢呋喃(THF)-醋酸中进行还原。将所得的粗品用2M盐酸(150mL)和乙醚进行处理。将所得的白色沉淀滤出，得到14.7g盐酸盐形式的标题化合物。将该水溶液用饱和碳酸氢钠(NaHCO3)水溶液中和，过滤，得到4.58g浅灰色固体形式的标题化合物纯品。1H NB(DMSO-d6)：5.54(br.s，2H，NH2)，6.53(dd，1H)，6.70(d，1H)，7.02(d，1H)，10.79(br.s，1H9 NHCO)。LC/MS(m/z)239.8([M+H]+)；RT＝1.67，(UV)100％。To a suspension of 4-nitro-2-chloroaniline (17.2 g, 0.1 mol) in 1,2-dichloroethane (100 mL) was added trifluoroacetic anhydride (16 mL, 0.113 mol). After 5 minutes, the resulting yellow solution was evaporated in vacuo. The resulting yellow N-(4-nitro-2-chlorophenyl)-2,2,2-trifluoroacetamide solid was reduced with Zn-powder in tetrahydrofuran (THF)-acetic acid as described above . The resulting crude product was treated with 2M hydrochloric acid (150 mL) and diethyl ether. The resulting white precipitate was filtered off, yielding 14.7 g of the title compound as the hydrochloride salt. The aqueous solution was neutralized with saturated aqueous sodium bicarbonate ( NaHCO3 ) and filtered to afford 4.58 g of pure title compound as a light gray solid. 1H NB (DMSO-d 6 ): 5.54 (br.s, 2H, NH 2 ), 6.53 (dd, 1H), 6.70 (d, 1H), 7.02 (d, 1H), 10.79 (br.s, 1H9 NHCO ). LC/MS (m/z) 239.8 ([M+H] + ); RT = 1.67, (UV) 100%.

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2，2，2-三氟乙酰胺。N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2,2,2-trifluoroacetamide.

将N-(4-氨基-2-氯苯基)-2，2，2-三氟乙酰胺(4.567g，19.14mmol)和5-氯-噻吩-2-甲醛(carboxaldehyde)(3.97g，27.1mmol)在无水乙醇(50mL)中的溶液加热至回流加热15分钟并将其在70℃下真空蒸发(0.1mbar，30分钟)。将所得的结晶固体形式的亚胺粗品溶解于甲醇中，然后逐份加入位于甲醇(50mL)和醋酸(9mL)中的氰基硼氢化钠(NaBH3CN)。将所得的反应混合物在室温下搅拌60分钟并将其真空蒸发至小体积。在将该浓溶液用水淬熄并在30分钟后过滤，得到6.98g(收率为99％)褐色-黄色固体形式的标题化合物。1H NMR(DMSO-d6)：4.43(d，2H)，6.63(dd，1H)，6.77(d，1H)，6.79(t，1H，NH)，6.94(d，1H)，6.97(d，1H)，7.10(d，1H)，10.85(br.s，1H，NHCO)。LC/MS(m/z)367.9(M+)；RT＝3.36，(UV，ELSD)99％，100％。N-(4-amino-2-chlorophenyl)-2,2,2-trifluoroacetamide (4.567g, 19.14mmol) and 5-chloro-thiophene-2-carbaldehyde (carboxaldehyde) (3.97g, 27.1 A solution of mmol) in absolute ethanol (50 mL) was heated to reflux for 15 minutes and evaporated at 70° C. in vacuo (0.1 mbar, 30 minutes). The resulting crude imine as a crystalline solid was dissolved in methanol, then sodium cyanoborohydride ( NaBH3CN ) in methanol (50 mL) and acetic acid (9 mL) was added portionwise. The resulting reaction mixture was stirred at room temperature for 60 minutes and evaporated in vacuo to a small volume. After the concentrated solution was quenched with water and filtered after 30 minutes, 6.98 g (99% yield) of the title compound was obtained as a brown-yellow solid. 1 H NMR (DMSO-d 6 ): 4.43(d, 2H), 6.63(dd, 1H), 6.77(d, 1H), 6.79(t, 1H, NH), 6.94(d, 1H), 6.97(d , 1H), 7.10 (d, 1H), 10.85 (br.s, 1H, NHCO). LC/MS (m/z) 367.9 (M + ); RT = 3.36, (UV, ELSD) 99%, 100%.

N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2，2，2-三氟乙酰胺.N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2,2,2-trifluoroacetamide.

在30分钟内，在搅拌的情况下向N{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2，2，2-三氟乙酰胺(3.28g，8.88mmol)、37％甲醛水溶液(5mL)、和醋酸(3mL)的混合物中滴加位于甲醇(10mL)中的氰基硼氢化钠(NaBH3CN)(1.1g)。使该反应混合物在室温下静置2小时并将其倾倒到水中。在该油状物固化后，将其滤出，用水洗涤并将其真空干燥，得到3.26g浅黄色-褐色固体。收率为95％。1HNMR(DMSO-d6)：2.97(s，3H，NMe)，4.72(s，2H)，6.82(m，1H)，6.91(m，2H)，6.97(d，1H)，7.21(d，1H)，10.92(br.s，1H，NHCO)。LC/MS(m/z)382.0(M+)；RT＝3.66，(UV，ELSD)85％，98％。To N{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2,2,2-trifluoroethane with stirring over 30 minutes Sodium cyanoborohydride (NaBH3CN) ( 1.1 g) in methanol (10 mL) was added dropwise to a mixture of amide (3.28 g, 8.88 mmol), 37% aqueous formaldehyde (5 mL), and acetic acid (3 mL). The reaction mixture was allowed to stand at room temperature for 2 hours and poured into water. After the oil solidified, it was filtered off, washed with water and dried in vacuo to yield 3.26 g of a pale yellow-brown solid. The yield is 95%. 1 HNMR (DMSO-d 6 ): 2.97(s, 3H, NMe), 4.72(s, 2H), 6.82(m, 1H), 6.91(m, 2H), 6.97(d, 1H), 7.21(d, 1H), 10.92 (br.s, 1H, NHCO). LC/MS (m/z) 382.0 (M + ); RT = 3.66, (UV, ELSD) 85%, 98%.

(5-氯-噻吩-2-基甲基)-[3-氯-4-(2，2，2-三氟-乙酰基氨基)-苯基]-氨基甲酸叔-丁酯.(5-Chloro-thiophen-2-ylmethyl)-[3-chloro-4-(2,2,2-trifluoro-acetylamino)-phenyl]-carbamic acid tert-butyl ester.

将N-(2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2，2，2-三氟乙酰胺(2.219g，6.01mmol)、重碳酸二-叔-丁酯(2g)、和乙腈(3mL)的混合物加热至+80℃直至反应完全(36小时)。在此期间，加入另外数量的重碳酸二-叔-丁酯(2×1.5g)。将所得的反应混合物真空蒸发(80℃，0.1mbar)，得到标题化合物粗品，将其不进行进一步纯化地用于下一步。1H NMR(DMSO-d6)：1.44(s，9H)，4.94(s，2H)，6.81(d，1H)，6.93(d，1H)，7.25(dd，1H)，7.43(d，1H)，7.50(d，1H)，11.24(br.s，1H，NHCO)。LC/MS(m/z)366.9([M-Boc]+)；RT＝3.99，(UV，ELSD)87％，96％。N-(2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2,2,2-trifluoroacetamide (2.219 g, 6.01 mmol), A mixture of di-tert-butyl bicarbonate (2 g), and acetonitrile (3 mL) was heated to +80° C. until the reaction was complete (36 hours). During this time, an additional amount of di-tert-butyl bicarbonate (2 × 1.5 g). The resulting reaction mixture was evaporated in vacuo (80 °C, 0.1 mbar) to give the crude title compound, which was used in the next step without further purification. 1 H NMR (DMSO-d 6 ): 1.44 (s , 9H), 4.94(s, 2H), 6.81(d, 1H), 6.93(d, 1H), 7.25(dd, 1H), 7.43(d, 1H), 7.50(d, 1H), 11.24(br. s, 1H, NHCO). LC/MS (m/z) 366.9 ([M-Boc] + ); RT = 3.99, (UV, ELSD) 87%, 96%.

2-氯-N(4)-(5-氯-噻吩-2-基甲基)-N(4)-甲基-苯-1，4-二胺。2-Chloro-N(4)-(5-chloro-thiophen-2-ylmethyl)-N(4)-methyl-benzene-1,4-diamine.

向N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2，2，2-三氟乙酰胺(3.118g)在甲醇(MeOH)(50mL)中的溶液中加入碳酸钾(K2CO3)(6.4g)在水(25mL)中的溶液并将该反应混合物在室温下搅拌至反应完全(24小时)。将所得的反应混合物用乙酸乙酯进行萃取，用饱和碳酸氢钠(NaHCO3)水溶液进行洗涤并将其蒸发，得到2.26g暗褐色油状物。将其不进行进一步纯化地用于下一步。1H NMR(DMSO-d6)：2.71(s，3H，NMe)，4.47(s，2H)，4.71(br.s，2H，NH2)，6.67-6.75(m，3H)，6.82(d，1H)，6.93(d，1H)。LC/MS(m/z)288.0([M+H]+)；RT＝2.07，(UV，ELSD)85％，98％。To N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2,2,2-trifluoroacetamide (3.118g) To a solution in methanol (MeOH) (50 mL) was added a solution of potassium carbonate ( K2CO3 ) (6.4 g ) in water (25 mL) and the reaction mixture was stirred at room temperature until complete (24 hours). The resulting reaction mixture was extracted with ethyl acetate, washed with saturated aqueous sodium bicarbonate ( NaHCO3 ) and evaporated to give 2.26 g of a dark brown oil. It was used in the next step without further purification. 1 H NMR (DMSO-d 6 ): 2.71(s, 3H, NMe), 4.47(s, 2H), 4.71(br.s, 2H, NH 2 ), 6.67-6.75(m, 3H), 6.82(d , 1H), 6.93(d, 1H). LC/MS (m/z) 288.0 ([M+H] + ); RT = 2.07, (UV, ELSD) 85%, 98%.

类似地制备下面的化合物：The following compounds were prepared analogously:

(4-氨基-3-氯苯基)-(5-氯-噻吩-2-基甲基)-氨基甲酸叔-丁酯。(4-Amino-3-chlorophenyl)-(5-chloro-thiophen-2-ylmethyl)-carbamic acid tert-butyl ester.

IH NMR(DMSO-d6)：1.39(br.s，9H，叔-Bu)，4.74(s，2H)，5.35(br.s，2H，NH2)，6.67-6.74(m，2H)，6.77(br.d，1H)，6.90(d，1H)，6.97(d，1H)。LC/MS(m/z)271.9([M-Boc]+)；RT＝3.73，(UV，ELSD)77％，97％。IH NMR (DMSO-d 6 ): 1.39 (br.s, 9H, tert-Bu), 4.74 (s, 2H), 5.35 (br.s, 2H, NH 2 ), 6.67-6.74 (m, 2H), 6.77 (br.d, 1H), 6.90 (d, 1H), 6.97 (d, 1H). LC/MS (m/z) 271.9 ([M-Boc] + ); RT = 3.73, (UV, ELSD) 77%, 97%.

4-氟-2-异丙氧基-1-硝基苯4-fluoro-2-isopropoxy-1-nitrobenzene

将5-氟-2-硝基苯酚(48g)溶解于无水四氢呋喃(THF)(300mL)中。向其中加入三苯基膦(88g)和2-丙醇(47mL)，并将所得的混合物冷却至0℃。向其中滴加偶氮甲酸二异丙酯(66mL)。将所得的混合物加温至室温并将其搅拌一整夜。在真空下蒸发掉溶剂并将所得的混合物用二氧化硅过滤(用庚烷/乙酸乙酯1∶1进行洗脱)。将溶剂真空蒸发并将所得的混合物用庚烷/乙酸乙酯(1∶1)重结晶。通过过滤将有机相与该结晶固体分离，将溶剂真空蒸发，并将剩余的产物用闪柱色谱纯化(硅胶，庚烷/乙酸乙酯9∶1)，得到无色油状物形式的标题化合物(47.2g，78％)。1H NMR(DMSO-d6)：1.30(d，6H)，4.85(h，1H)，6.93(m，1H)，7.34(dd，1H)，7.96(dd，1H)。5-Fluoro-2-nitrophenol (48 g) was dissolved in anhydrous tetrahydrofuran (THF) (300 mL). Triphenylphosphine (88 g) and 2-propanol (47 mL) were added thereto, and the resulting mixture was cooled to 0°C. Diisopropyl azocarboxylate (66 mL) was added dropwise thereto. The resulting mixture was warmed to room temperature and stirred overnight. The solvent was evaporated under vacuum and the resulting mixture was filtered over silica (eluting with heptane/ethyl acetate 1:1). The solvent was evaporated in vacuo and the resulting mixture was recrystallized from heptane/ethyl acetate (1:1). The organic phase was separated from the crystalline solid by filtration, the solvent was evaporated in vacuo and the remaining product was purified by flash chromatography (silica gel, heptane/ethyl acetate 9:1) to give the title compound as a colorless oil ( 47.2 g, 78%). 1 H NMR (DMSO-d 6 ): 1.30 (d, 6H), 4.85 (h, 1H), 6.93 (m, 1H), 7.34 (dd, 1H), 7.96 (dd, 1H).

相似地制备下面的化合物：The following compounds were similarly prepared:

2-环戊氧基-4-氟-1-硝基苯。2-cyclopentyloxy-4-fluoro-1-nitrobenzene.

1H NMR(DMSO-d6)：1.57-1.78(m，6H)，1.86-1.94(m，2H)，6.90-6.97(m，1H)，7.27-7.32(m，1H)，7.98(dd，1H)。 1 H NMR (DMSO-d 6 ): 1.57-1.78 (m, 6H), 1.86-1.94 (m, 2H), 6.90-6.97 (m, 1H), 7.27-7.32 (m, 1H), 7.98 (dd, 1H).

2-苄氧基-4-氟-1-硝基苯。2-Benzyloxy-4-fluoro-1-nitrobenzene.

1H NMR(DMSO-d6)：5.33(s，2H)，6.96-7.04(m，1H)，7.32-7.49(m，6H)，8.04(dd，1H)。 1 H NMR (DMSO-d 6 ): 5.33 (s, 2H), 6.96-7.04 (m, 1H), 7.32-7.49 (m, 6H), 8.04 (dd, 1H).

(4-氟苄基)-(3-异丙氧基-4-硝基苯基)-(甲基)-胺(4-fluorobenzyl)-(3-isopropoxy-4-nitrophenyl)-(methyl)-amine

将4-氟-2-异丙氧基-1-硝基苯(1.0g)溶解于无水二甲基亚砜(25mL)中。向其中加入碳酸钾(1.4g)和(4-氟苄基)-(甲基)-胺(0.84g)。将所得的混合物加热至90℃加热一整夜。在冷却至室温后，向其中加入水(75mL)，将所得的混合物用乙酸乙酯(3×75mL)进行萃取。将有机相用硫酸钠进行干燥，过滤，并将其真空蒸发，得到略带黄色的固体形式的标题化合物(1.6g，100％)。LC-MS(m/z)319.1([M+H]+)；RT＝3.43，(UV，ELSID)85％，96％。1H NMR(DMSO-d6)：1.21(d，6H)，3.18(s，3H)，4.71(m，1H)，4.73(s，2H)，6.26(d，1H)，6.41(dd，1H)，7.17(m，2H)，7.25(m，2H)，7.84(d，1H)，4-Fluoro-2-isopropoxy-1-nitrobenzene (1.0 g) was dissolved in anhydrous dimethylsulfoxide (25 mL). Potassium carbonate (1.4 g) and (4-fluorobenzyl)-(methyl)-amine (0.84 g) were added thereto. The resulting mixture was heated to 90°C overnight. After cooling to room temperature, water (75 mL) was added thereto, and the resulting mixture was extracted with ethyl acetate (3 x 75 mL). The organic phase was dried over sodium sulfate, filtered and evaporated in vacuo to give the title compound (1.6 g, 100%) as a yellowish solid. LC-MS (m/z) 319.1 ([M+H] + ); RT = 3.43, (UV, ELSID) 85%, 96%. 1 H NMR (DMSO-d 6 ): 1.21(d, 6H), 3.18(s, 3H), 4.71(m, 1H), 4.73(s, 2H), 6.26(d, 1H), 6.41(dd, 1H ), 7.17(m, 2H), 7.25(m, 2H), 7.84(d, 1H),

相似地制备下面的化合物：The following compounds were similarly prepared:

(3-苄氧基-4-硝基苯基)(4-氟苄基)甲基胺。(3-benzyloxy-4-nitrophenyl)(4-fluorobenzyl)methylamine.

LC-MS(m/z)320.9([M+H-NO2]+)；RT＝3.54，(UV，ELSD)96％，100％。LC-MS (m/z) 320.9 ([M+H-NO 2 ] + ); RT=3.54, (UV, ELSD) 96%, 100%.

(3-环戊氧基-4-硝基苯基)(4-氟苄基)甲基胺。(3-cyclopentyloxy-4-nitrophenyl)(4-fluorobenzyl)methylamine.

LC-MS(m/z)299.2([M+H-NO2]+)RT＝3.64，(UV，ELSD)96％，100％。LC-MS (m/z) 299.2 ([M+H-NO 2 ] + ) RT=3.64, (UV, ELSD) 96%, 100%.

4-(4-氟苄基)-(甲基)-氨基-2-异丙氧基苯胺4-(4-Fluorobenzyl)-(methyl)-amino-2-isopropoxyaniline

将(4-氟苄基)-(3-异丙氧基-4-硝基苯基)-(甲基)-胺(1.60g)溶解于甲醇(50mL)中。甲酸铵(1.91g)和钯(10％，位于炭上，0.21g)，并将该混合物在室温下搅拌1.5小时，将该反应混合物过滤并将溶剂真空蒸发。将残余物溶解于少量甲醇中并向其中加入浓水性氢氧化钠(2mL)。将所得的混合物通过硅胶柱进行过滤(用乙酸乙酯作为洗脱剂)，将所得的溶液真空蒸发，得到暗色油状物形式的标题化合物粗品(0.76g)，将其直接用于下一步。LC-MS(m/z)288.9([M+H]+)；RT＝1.91，(UV，ELSD)80％，72％，(4-Fluorobenzyl)-(3-isopropoxy-4-nitrophenyl)-(methyl)-amine (1.60 g) was dissolved in methanol (50 mL). Ammonium formate (1.91 g) and palladium (10% on charcoal, 0.21 g), and the mixture was stirred at room temperature for 1.5 hours, the reaction mixture was filtered and the solvent was evaporated in vacuo. The residue was dissolved in a small amount of methanol and concentrated aqueous sodium hydroxide (2 mL) was added thereto. The resulting mixture was filtered through a silica gel column (ethyl acetate as eluent) and the resulting solution was evaporated in vacuo to give the crude title compound (0.76 g) as a dark oil which was used directly in the next step. LC-MS (m/z) 288.9 ([M+H] + ); RT=1.91, (UV, ELSD) 80%, 72%,

(5-氯-噻吩-2-基甲基)-(甲基)-(3-甲基-4-硝基苯基)-胺(5-Chloro-thiophen-2-ylmethyl)-(methyl)-(3-methyl-4-nitrophenyl)-amine

将5-氯-噻吩-2-甲醛(1.61g，11.0mmol)、3-甲基-4-硝基苯胺(1.52g，10.0mmol)、和Amberlite IRC-84(100mg，H+型)在邻-二甲苯(40mL)中的混悬液在氮气下在140℃下加热5小时。在冷却至室温后，通过过滤除去树脂并蒸发掉易挥发物。将残余物溶解于乙腈(40mL)中并一次向其中加入所有的氰基硼氢化钠(1.26g，20.0mmol)，然后，在15分钟内以分成几份的形式向其中加入醋酸(1mL)，然后向其中加入甲醛溶液(37％的水溶液，2.23mL，30.0mmol)并将该混合物再搅拌30分钟。蒸发掉易挥发物并将残余物在饱和碳酸氢钠水溶液(100mL)和乙酸乙酯(100mL)之间进行分配，将水相用乙酸乙酯(50mL)进行萃取。将有机层用硫酸钠进行干燥，蒸发掉溶剂，用NMR对残余物进行分析。不完全的N-甲基化要求将该还原性胺化步骤重复进行三次(使用甲醛溶液，7.4mL，100mmol，和氰基硼氢化钠，2.07g，33mmol)，之后获得了完全转化。此后，将该粗品用FlashMaster系统纯化(二氧化硅，用庚烷/乙酸乙酯混合物进行洗脱)，得到黄色油状物形式的标题化合物(1.85g，62％)。1H NMR(CDCl3)：2.64(s，3H)，3.11(s，3H)，4.66(s，3H)，6.52(d，1H)，6.60(dd，1H)，6.69(d，1H)，6.77(d，1H)，8.10(d，1H)。5-Chloro-thiophene-2-carbaldehyde (1.61g, 11.0mmol), 3-methyl-4-nitroaniline (1.52g, 10.0mmol), and Amberlite IRC-84 (100mg, H + form) in o - A suspension in xylene (40 mL) was heated at 140° C. for 5 hours under nitrogen. After cooling to room temperature, the resin was removed by filtration and volatiles were evaporated. The residue was dissolved in acetonitrile (40 mL) and sodium cyanoborohydride (1.26 g, 20.0 mmol) was added all at once, then acetic acid (1 mL) was added in portions over 15 minutes, Formaldehyde solution (37% in water, 2.23 mL, 30.0 mmol) was then added thereto and the mixture was stirred for another 30 minutes. The volatiles were evaporated and the residue was partitioned between saturated aqueous sodium bicarbonate (100 mL) and ethyl acetate (100 mL), the aqueous phase was extracted with ethyl acetate (50 mL). The organic layer was dried over sodium sulfate, the solvent was evaporated and the residue was analyzed by NMR. Incomplete N-methylation required that the reductive amination step be repeated three times (using formaldehyde solution, 7.4 mL, 100 mmol, and sodium cyanoborohydride, 2.07 g, 33 mmol), after which complete conversion was obtained. After this time, the crude product was purified on a FlashMaster system (silica, eluting with heptane/ethyl acetate mixtures) to afford the title compound (1.85 g, 62%) as a yellow oil. 1 H NMR (CDCl 3 ): 2.64(s, 3H), 3.11(s, 3H), 4.66(s, 3H), 6.52(d, 1H), 6.60(dd, 1H), 6.69(d, 1H), 6.77(d,1H), 8.10(d,1H).

N-(4)-(5-氯-噻吩-2-基甲基)-2，N(4)-二甲基-苯-1，4-二胺N-(4)-(5-Chloro-thiophen-2-ylmethyl)-2,N(4)-dimethyl-benzene-1,4-diamine

向(5-氯-噻吩-2-基甲基)-(甲基)-(3-甲基-4-硝基苯基)-胺(1.85g，6.23mmol)和铁粉(2.09g，37.4mmol)在乙醇(60mL)中的混悬液中加入6N HCl(12.5mL，75mmol)，将该混合物在+60℃下强烈搅拌50分钟。然后，将其倾倒到饱和碳酸氢钠水溶液(200mL)中，向其中加入足够的碳酸钠以获得＞10的pH。将所得的混合物用乙酸乙酯进行萃取(200mL，然后2×100mL)，将萃取物用硫酸钠进行干燥并蒸发掉挥发性物质。将残余物用FlashMaster系统纯化(二氧化硅，用庚烷/乙酸乙酯混合物进行洗脱)，得到褐色油状物形式的标题化合物(1.51g，91％)。1H NMR(CDCl3)：2.16(s，3H)，2.79(s，3H)，3.32(br.s，2H)，4.39(s，3H)，6.58-6.65(m，4H)，6.72(d，1H)。To (5-chloro-thiophen-2-ylmethyl)-(methyl)-(3-methyl-4-nitrophenyl)-amine (1.85g, 6.23mmol) and iron powder (2.09g, 37.4 mmol) in ethanol (60 mL) was added 6N HCl (12.5 mL, 75 mmol) and the mixture was vigorously stirred at +60°C for 50 minutes. It was then poured into saturated aqueous sodium bicarbonate (200 mL), to which enough sodium carbonate was added to obtain a pH >10. The resulting mixture was extracted with ethyl acetate (200 mL, then 2 x 100 mL), the extract was dried over sodium sulfate and the volatiles were evaporated. The residue was purified on the FlashMaster system (silica, eluting with heptane/ethyl acetate mixtures) to give the title compound (1.51 g, 91%) as a brown oil. 1 H NMR (CDCl 3 ): 2.16(s, 3H), 2.79(s, 3H), 3.32(br.s, 2H), 4.39(s, 3H), 6.58-6.65(m, 4H), 6.72(d , 1H).

由XXXIV进行的通式XXXV、XXXVI、和XIX的中间体的合成：Synthesis of intermediates of general formula XXXV, XXXVI, and XIX by XXXIV:

(3-甲基-4-硝基苯基)-(4-三氟甲基苄基)-胺(3-Methyl-4-nitrophenyl)-(4-trifluoromethylbenzyl)-amine

将4-三氟甲基苯甲醛(8191L，6.00mmol)、3-甲基-4-硝基苯胺(609mg，4.00mmol)、和Amberlite IRC-84(200mg，H+型)在邻-二甲苯(4mL)中的混悬液在氮气下，在140℃下加热6小时。然后，将其冷却至室温，用乙酸乙酯(5mL)稀释，用硫酸钠进行干燥，过滤，然后蒸发掉挥发性物质。将残余物溶解于乙腈(20mL)中并一次向其中加入所有的氰基硼氢化钠(503mg，8.00mmol)，然后在15分钟内以分成几份的形式加入醋酸(1mL)。在又过了30分钟后，蒸发掉溶剂并将残余物在乙酸乙酯(50mL)、盐水(25mL)、和10％碳酸钾水溶液(25mL)之间进行分配。将有机层用硫酸钠进行干燥，蒸发掉溶剂，并将残余物在FlashMaster系统上进行纯化(二氧化硅，用庚烷/乙酸乙酯混合物进行洗脱)，得到黄色粉末形式的标题化合物(1.02g，82％)。1HNMR(CDCl3)：2.59(s，3H)，4.50(d，2H)，4.76(br.t，1H)，6.40(d，1H)，6.43(dd，1H)，7.45(d，2H)，7.63(d，2H)，8.05(d，1H)。4-Trifluoromethylbenzaldehyde (8191L, 6.00mmol), 3-methyl-4-nitroaniline (609mg, 4.00mmol), and Amberlite IRC-84 (200mg, H + form) were dissolved in o-xylene (4 mL) was heated at 140° C. for 6 hours under nitrogen. Then, it was cooled to room temperature, diluted with ethyl acetate (5 mL), dried over sodium sulfate, filtered, and the volatiles were evaporated. The residue was dissolved in acetonitrile (20 mL) and to it was added sodium cyanoborohydride (503 mg, 8.00 mmol) all at once, followed by acetic acid (1 mL) in portions over 15 minutes. After another 30 minutes, the solvent was evaporated and the residue was partitioned between ethyl acetate (50 mL), brine (25 mL), and 10% aqueous potassium carbonate (25 mL). The organic layer was dried over sodium sulfate, the solvent was evaporated and the residue was purified on a FlashMaster system (silica, eluting with a heptane/ethyl acetate mixture) to give the title compound (1.02 g, 82%). 1 HNMR (CDCl 3 ): 2.59(s, 3H), 4.50(d, 2H), 4.76(br.t, 1H), 6.40(d, 1H), 6.43(dd, 1H), 7.45(d, 2H) , 7.63(d, 2H), 8.05(d, 1H).

(3-甲基-4-硝基苯基)-(4-三氟甲基苄基)-氨基甲酸叔-丁酯(3-Methyl-4-nitrophenyl)-(4-trifluoromethylbenzyl)-carbamic acid tert-butyl ester

将(3-甲基-4-硝基苯基)-(4-三氟甲基苄基)-胺(1.02g，3.29mmol)、重碳酸二-叔-丁酯(1.08g，4.93mmol)、二甲基氨基吡啶(201mg，1.64mmol)、和三乙胺(687μL，4.93mmol)在乙腈(20mL)中的溶液在一个开口烧瓶中在室温下搅拌18小时(以除去二氧化碳)。蒸发掉挥发性物质并将残余物溶解于乙酸乙酯(50mL)中。将这种溶液用饱和氯化铵水溶液洗涤(2×50mL)，用硫酸钠进行干燥，蒸发掉挥发性物质，并将残余物在FlashMaster系统上进行纯化(二氧化硅，用烷/乙酸乙酯混合物进行洗脱)，得到浅黄色粘性油状物形式的标题化合物(1.17g，86％)，其保留有痕量的庚烷。(3-Methyl-4-nitrophenyl)-(4-trifluoromethylbenzyl)-amine (1.02g, 3.29mmol), di-tert-butyl dicarbonate (1.08g, 4.93mmol) , dimethylaminopyridine (201 mg, 1.64 mmol), and triethylamine (687 μL, 4.93 mmol) in acetonitrile (20 mL) was stirred in an open flask at room temperature for 18 hours (to remove carbon dioxide). Volatile materials were evaporated and the residue was dissolved in ethyl acetate (50 mL). This solution was washed with saturated aqueous ammonium chloride (2 x 50 mL), dried over sodium sulfate, the volatiles were evaporated, and the residue was purified on a FlashMaster system (silica, with alkane/ethyl acetate The mixture was eluted) to give the title compound (1.17 g, 86%) as a light yellow viscous oil with traces of heptane remaining.

1H NMR(CDCl3)：1.44(s，9H)，2.58(s，3H)，4.95(s，2H)，7.16(dd，1H)，7.21(d，1H)，7.34(d，2H)，7.60(d，2H)，7.96(d，1H)。 1 H NMR (CDCl 3 ): 1.44(s, 9H), 2.58(s, 3H), 4.95(s, 2H), 7.16(dd, 1H), 7.21(d, 1H), 7.34(d, 2H), 7.60 (d, 2H), 7.96 (d, 1H).

(4-氨基-3-甲基苯基)-(4-三氟甲基苄基)-氨基甲酸叔-丁酯(4-Amino-3-methylphenyl)-(4-trifluoromethylbenzyl)-carbamic acid tert-butyl ester

将Na2S2O4(3.00g，17.2mmol)在水(20mL)中的溶液加入到(3-甲基-4-硝基苯基)-(4-三氟甲基苄基)-氨基甲酸叔-丁酯(1.41g，3.44mmol)在四氢呋喃(20mL)中的溶液中，并将所得的混合物在+55℃下搅拌20小时。在冷却至室温后，将水相用碳酸钾饱和，分离出有机层，并将水层用乙酸乙酯(2×20mL)萃取。将所合并得有机层用硫酸钠进行干燥，蒸发掉溶剂，并将残余物在FlashMaster系统上进行纯化(二氧化硅，用庚烷/乙酸乙酯混合物进行洗脱)，得到白色固体形式的标题化合物(1.09g，83％)。A solution of Na 2 S 2 O 4 (3.00 g, 17.2 mmol) in water (20 mL) was added to (3-methyl-4-nitrophenyl)-(4-trifluoromethylbenzyl)-amino tert-Butyl formate (1.41 g, 3.44 mmol) was dissolved in tetrahydrofuran (20 mL), and the resulting mixture was stirred at +55°C for 20 hours. After cooling to room temperature, the aqueous phase was saturated with potassium carbonate, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2 x 20 mL). The combined organic layers were dried over sodium sulfate, the solvent was evaporated and the residue was purified on a FlashMaster system (silica, eluting with a heptane/ethyl acetate mixture) to afford the title as a white solid Compound (1.09 g, 83%).

1H NMR(CDCl3)：1.41(s，9H)，2.10(s，3H)，3.59(br.s，2H)，4.78(s，2H)，6.56(d，1H)，6.76(br.s，2H)，7.36(d，2H)，7.55(d，2H)。 1 H NMR (CDCl 3 ): 1.41(s, 9H), 2.10(s, 3H), 3.59(br.s, 2H), 4.78(s, 2H), 6.56(d, 1H), 6.76(br.s , 2H), 7.36(d, 2H), 7.55(d, 2H).

本发明的化合物Compounds of the invention

实施例1Example 1

1a{4-[(苯并呋喃-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯。1a {4-[(Benzofuran-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester.

将0.1M(4-氨基-2-甲基苯基)-氨基甲酸丙酯(0.35mL，0.035mmol)的四氢呋喃(THF)溶液和0.1M苯并呋喃-2-甲醛(0.35mL)的四氢呋喃(THF)溶液的混合物在55℃下保持60分钟。在真空下除去挥发性物质。向所得的残余物中加入位于甲醇中的0.2M氰基硼氢化钠(NaBH3CN)(0.5mL)和醋酸(0.03mL)。在将其声处理60分钟后，将该反应混合物真空蒸发并用制备LC/MS对标题化合物进行分离，得到5.1mg无色固体。收率为43％。LC/MS(m/z)339.2([M+H]+)；RT＝2.92，(UV，ELSD)94％，94％。A solution of 0.1 M (4-amino-2-methylphenyl)-propylcarbamate (0.35 mL, 0.035 mmol) in tetrahydrofuran (THF) and 0.1 M benzofuran-2-carbaldehyde (0.35 mL) in THF ( The mixture of THF) solutions was maintained at 55°C for 60 minutes. Volatile materials were removed under vacuum. To the resulting residue were added 0.2M sodium cyanoborohydride ( NaBH3CN ) in methanol (0.5 mL) and acetic acid (0.03 mL). After sonicating for 60 min, the reaction mixture was evaporated in vacuo and the title compound was isolated by preparative LC/MS to give 5.1 mg of a colorless solid. The yield was 43%. LC/MS (m/z) 339.2 ([M+H] + ); RT = 2.92, (UV, ELSD) 94%, 94%.

1b{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸乙酯。1b{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamate ethyl ester.

LC/MS(m/z)323.9(M+)；RT＝2.67，(UV，ELSD)94％，100％。LC/MS (m/z) 323.9 (M + ); RT = 2.67, (UV, ELSD) 94%, 100%.

1c{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸乙酯。1c {4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamate ethyl ester.

LC/MS(m/z)340.0(M+)；RT＝2.87，(UV，ELSD)91％，100％。LC/MS (m/z) 340.0 (M + ); RT = 2.87, (UV, ELSD) 91%, 100%.

1d{2-甲基-4-[(5-苯基-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸乙酯。1d{2-Methyl-4-[(5-phenyl-thiophen-2-ylmethyl)-amino]-phenyl}-carbamate ethyl ester.

LC/MS(m/z)365.3([M-H]+)；RT＝2.89，(UV，ELSD)97％，99％。LC/MS (m/z) 365.3 ([MH] + ); RT = 2.89, (UV, ELSD) 97%, 99%.

1e[4-(4-异丙基-苄基氨基)-2-甲基苯基]-氨基甲酸乙酯。1e[4-(4-Isopropyl-benzylamino)-2-methylphenyl]-carbamate ethyl ester.

LC/MS(m/z)326.0(M+)；RT＝2.50，(UV，ELSD)84％，98％。LC/MS (m/z) 326.0 (M + ); RT = 2.50, (UV, ELSD) 84%, 98%.

1f[4-(4-氟-苄基氨基)-2-甲基苯基]-氨基甲酸丙酯。1f [4-(4-Fluoro-benzylamino)-2-methylphenyl]-carbamate propyl ester.

LC/MS(m/z)317.1([M+H]+)；RT＝2.32，(UV，ELSD)82％，96％。LC/MS (m/z) 317.1 ([M+H] + ); RT = 2.32, (UV, ELSD) 82%, 96%.

1g(4-{[4-(4-氯-苯磺酰基)-3-甲基-噻吩-2-基甲基]-氨基}-2-甲基苯基)-氨基甲酸丙酯。1 g (4-{[4-(4-Chloro-benzenesulfonyl)-3-methyl-thiophen-2-ylmethyl]-amino}-2-methylphenyl)-carbamate propyl ester.

LC/MS(m/z)493.0([M+H]+)；RT＝3.18，(UV，ELSD)91％，97％。LC/MS (m/z) 493.0 ([M+H] + ); RT = 3.18, (UV, ELSD) 91%, 97%.

1h{4-[(5-甲基-噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯。1h {4-[(5-Methyl-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamate propyl ester.

LC/MS(m/z)317.1([M-H]+)；RT＝2.41，(UV，ELSD)76％，93％。LC/MS (m/z) 317.1 ([MH] + ); RT = 2.41, (UV, ELSD) 76%, 93%.

1i{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯。1i {4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester.

LC/MS(m/z)382.0(M+)；RT＝2.96，(UV，ELSD)70％，87％。LC/MS (m/z) 382.0 (M + ); RT = 2.96, (UV, ELSD) 70%, 87%.

1j{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯。1j {4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester.

LC/MS(m/z)338.2(M+)；RT＝2.92，(UV，ELSD)85％，84％。LC/MS (m/z) 338.2 (M + ); RT = 2.92, (UV, ELSD) 85%, 84%.

1k{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯。lk{4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamate propyl ester.

LC/MS(m/z)355.1([M+H]+)；RT＝3.08，(UV，ELSD)93％，97％。LC/MS (m/z) 355.1 ([M+H] + ); RT = 3.08, (UV, ELSD) 93%, 97%.

11{2-甲基-4-[(5-苯基-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯。11{2-Methyl-4-[(5-phenyl-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)379.3([M-H]+)；RT＝3.08，(UV，ELSD)91％，95％。LC/MS (m/z) 379.3 ([MH] + ); RT = 3.08, (UV, ELSD) 91%, 95%.

1m[4-(4-异丙基-苄基氨基)-2-甲基苯基]-氨基甲酸丙酯。1 m Propyl [4-(4-isopropyl-benzylamino)-2-methylphenyl]-carbamate.

LC/MS(m/z)341.2([M+H]+)；RT＝2.71，(UV，ELSD)73％，96％。LC/MS (m/z) 341.2 ([M+H] + ); RT = 2.71, (UV, ELSD) 73%, 96%.

1o{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸乙酯。1o{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-carbamate ethyl ester.

LC/MS(m/z)389.0([M+H]+)；RT＝3.24，(UV，ELSD)98％，99％。LC/MS (m/z) 389.0 ([M+H] + ); RT = 3.24, (UV, ELSD) 98%, 99%.

1p{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸乙酯。1p{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-carbamate ethyl ester.

LC/MS(m/z)345.0([M+H]+)；RT＝3.21，(UV，ELSD)99％，100％。LC/MS (m/z) 345.0 ([M+H] + ); RT = 3.21, (UV, ELSD) 99%, 100%.

1q{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸乙酯。1q {4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-carbamate ethyl ester.

LC/MS(m/z)361.0([M+H]+)；RT＝3.28，(UV，ELSD)95％，100％。LC/MS (m/z) 361.0 ([M+H] + ); RT = 3.28, (UV, ELSD) 95%, 100%.

Ir[2-氯-4-(4-异丙基-苄基氨基)-苯基]-氨基甲酸乙酯。Ir[2-Chloro-4-(4-isopropyl-benzylamino)-phenyl]-urethane ethyl ester.

LC/MS(m/z)346.0(M+)；RT＝3.48，(UV，ELSD)95％，100％。LC/MS (m/z) 346.0 (M + ); RT = 3.48, (UV, ELSD) 95%, 100%.

1s[2-氯-4-(4-氟-苄基氨基)-苯基]-氨基甲酸丙酯。1s[2-Chloro-4-(4-fluoro-benzylamino)-phenyl]-carbamate propyl ester.

LC/MS(m/z)337.1([M+H]+)；RT＝3.20，(UV，ELSD)97％，99％。LC/MS (m/z) 337.1 ([M+H] + ); RT = 3.20, (UV, ELSD) 97%, 99%.

1t 2-氯-4-{[4-(4-氯-苯磺酰基)-3-甲基-噻吩-2-基甲基]-氨基}-苯基)-氨基甲酸丙酯。1t Propyl 2-chloro-4-{[4-(4-chloro-benzenesulfonyl)-3-methyl-thiophen-2-ylmethyl]-amino}-phenyl)-carbamate.

LC/MS(m/z)514.2([M+H]+)；RT＝3.52，(UV，ELSD)94％，99％。LC/MS (m/z) 514.2 ([M+H] + ); RT = 3.52, (UV, ELSD) 94%, 99%.

1u{4-[(5-甲基-噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸丙酯。1u {4-[(5-Methyl-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-carbamic acid propyl ester.

LC/MS(m/z)337.0([M-1]+)；RT＝3.27，(UV，ELSD)94％，100％。LC/MS (m/z) 337.0 ([M-1] + ); RT = 3.27, (UV, ELSD) 94%, 100%.

1v{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸丙酯。1v {4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-carbamate propyl ester.

LC/MS(m/z)403.9([M+H]+)；RT＝3.45，(UV，ELSD)99％，99％。LC/MS (m/z) 403.9 ([M+H] + ); RT = 3.45, (UV, ELSD) 99%, 99%.

1w{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯。1w {2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-carbamate propyl ester.

LC/MS(m/z)356.9([M-H]+)；RT＝3.43，(UV，ELSD)98％，95％。LC/MS (m/z) 356.9 ([MH] + ); RT = 3.43, (UV, ELSD) 98%, 95%.

1x{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸丙酯。1x {4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-carbamate propyl ester.

LC/MS(m/z)372.9([M-H]+)；RT＝3.49，(UV，ELSD)93％，99％。LC/MS (m/z) 372.9 ([MH] + ); RT = 3.49, (UV, ELSD) 93%, 99%.

1y{4-[(苯并呋喃-2-基甲基)-氨基]-2-氯苯基}-氨基甲酸丙酯。1y{4-[(Benzofuran-2-ylmethyl)-amino]-2-chlorophenyl}-carbamate propyl ester.

LC/MS(m/z)357.1([M-H]+)；RT＝3.37，(UV，ELSD)95％，98％。LC/MS (m/z) 357.1 ([MH] + ); RT = 3.37, (UV, ELSD) 95%, 98%.

1z{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-氰基苯基}-氨基甲酸乙酯。1z{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-cyanophenyl}-carbamate ethyl ester.

LC/MS(m/z)335.0(M+)；RT＝2.91，(UV，ELSD)99％，100％。LC/MS (m/z) 335.0 (M + ); RT = 2.91, (UV, ELSD) 99%, 100%.

1aa{4-[(苯并[b]噻吩-2-基甲基)-氨基]-2-甲氧基苯基}-氨基甲酸甲酯。1aa {4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-carbamate methyl ester.

LC/MS(m/z)341.1(M；RT＝2.62，(UV，ELSD)96％，100％。LC/MS (m/z) 341.1 (M; RT = 2.62, (UV, ELSD) 96%, 100%.

1ab{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-甲氧基苯基}-氨基甲酸异丙酯。1ab {4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-carbamic acid isopropyl ester.

LC/MS(m/z)400.0(M+)；RT＝2.93，(UV，ELSD)96％，100％。LC/MS (m/z) 400.0 (M + ); RT = 2.93, (UV, ELSD) 96%, 100%.

1ac{4-[(5-溴-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯。lac{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-phenyl}-carbamate propyl ester.

LC/MS(m/z)367.9(M+)；RT＝2.66，(UV，ELSD)87.0％，95.0％。LC/MS (m/z) 367.9 (M + ); RT = 2.66, (UV, ELSD) 87.0%, 95.0%.

1ad{4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯。1ad {4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-phenyl}-carbamate propyl ester.

LC/MS(m/z)324.0(M+)；RT＝2.60，(UV，ELSD)88.2％，96.5％。LC/MS (m/z) 324.0 (M + ); RT = 2.60, (UV, ELSD) 88.2%, 96.5%.

1ae[2-氰基-4-(4-异丙基苄基氨基)-苯基J-氨基甲酸乙酯。1ae[2-Cyano-4-(4-isopropylbenzylamino)-phenyl J-carbamate ethyl ester.

LC/MS(m/z)337.0(M+)；RT＝3.25，(UV，ELSD)90.8％，99.6％。LC/MS (m/z) 337.0 (M + ); RT = 3.25, (UV, ELSD) 90.8%, 99.6%.

1af[2-碘-4-(4-异丙基-苄基氨基)-苯基7-氨基甲酸丙酯。1af [Propyl 2-iodo-4-(4-isopropyl-benzylamino)-phenyl 7-carbamate.

LC/MS(m/z)452.0(M+)；RT＝3.72，(UV，ELSD)88.0％，97.7％。LC/MS (m/z) 452.0 (M + ); RT = 3.72, (UV, ELSD) 88.0%, 97.7%.

1ag[4-(4-叔-丁基-苄基氨基)-2-碘苯基]-氨基甲酸丙酯。1ag [4-(4-tert-butyl-benzylamino)-2-iodophenyl]-carbamate propyl ester.

LC/MS(m/z)465.9([M-1]+)；RT＝3.85，(UV，ELSD)86.6％，96.6％。LC/MS (m/z) 465.9 ([M-1] + ); RT = 3.85, (UV, ELSD) 86.6%, 96.6%.

1ah[2-碘-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸丙酯。1ah[2-iodo-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamate propyl ester.

LC/MS(m/z)479.0([M+H]+)；RT＝3.54，(UV，ELSD)97.7％，99.8％。LC/MS (m/z) 479.0 ([M+H] + ); RT = 3.54, (UV, ELSD) 97.7%, 99.8%.

1ai[2-碘-4-(4-甲基硫烷基-苄基氨基)-苯基]-氨基甲酸丙酯。1 ai [2-iodo-4-(4-methylsulfanyl-benzylamino)-phenyl]-carbamate propyl ester.

LC/MS(Z)454.8([M-1]+)RT＝3.38，(UV，ELSD)98.0％，99.8％。LC/MS (Z) 454.8 ([M-1] + ) RT = 3.38, (UV, ELSD) 98.0%, 99.8%.

1aj{2-碘-4-[4-(4-甲基哌嗪-1-基)-苄基氨基]-苯基}-氨基甲酸丙酯。1aj {2-Iodo-4-[4-(4-methylpiperazin-1-yl)-benzylamino]-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)508.9([M+H]+)；RT＝1.90，(UV，ELSD)62.0％，79.2％。LC/MS (m/z) 508.9 ([M+H] + ); RT = 1.90, (UV, ELSD) 62.0%, 79.2%.

1ak{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯。1ak{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl}-carbamate ethyl ester.

LC/MS(m/z)421.9(M+)；RT＝3.27，(IJV，ELSD)98.7％，98.5％。LC/MS (m/z) 421.9 (M + ); RT = 3.27, (IJV, ELSD) 98.7%, 98.5%.

1al{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯。1al{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl}-carbamate ethyl ester.

LC/MS(m/z)378.0(M+)；RT＝3.25，(UV，ELSD)97.7％，99.5％。LC/MS (m/z) 378.0 (M + ); RT = 3.25, (UV, ELSD) 97.7%, 99.5%.

1am[4-(4-叔-丁基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸乙酯。1 am [4-(4-tert-butyl-benzylamino)-2-trifluoromethyl-phenyl]-carbamate ethyl ester.

LC/MS(m/z)394.2(M+)；RT＝3.70，(UV，ELSD)90.2％，97.9％。LC/MS (m/z) 394.2 (M + ); RT = 3.70, (UV, ELSD) 90.2%, 97.9%.

1an[4-(4-甲基硫烷基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸乙酯。1an [4-(4-Methylsulfanyl-benzylamino)-2-trifluoromethyl-phenyl]-carbamate ethyl ester.

LC/MS(m/z)384.1(M+)；RT＝3.22，(UV，ELSD)84.4％，94.6％。LC/MS (m/z) 384.1 (M + ); RT = 3.22, (UV, ELSD) 84.4%, 94.6%.

1ao{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯。1ao{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)438.1([M+H]+)；RT＝3.47，(UV，ELSD)98.9％，99.9％。LC/MS (m/z) 438.1 ([M+H] + ); RT = 3.47, (UV, ELSD) 98.9%, 99.9%.

1ap[4-(4-异丙基苄基氨基)-2-三氟甲基-苯基]-氨基甲酸丙酯。1 ap [4-(4-isopropylbenzylamino)-2-trifluoromethyl-phenyl]-carbamate propyl ester.

LC/MS(m/z)393.3([M-1]+)；RT＝3.60，(UV，ELSD)71.3％，74.1％。LC/MS (m/z) 393.3 ([M-1] + ); RT = 3.60, (UV, ELSD) 71.3%, 74.1%.

1q[4-(4-叔-丁基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸丙酯。1q [4-(4-tert-butyl-benzylamino)-2-trifluoromethyl-phenyl]-carbamic acid propyl ester.

LC/MS(m/z)408.3(M+)；RT＝3.89，(UV，ELSD)91.1％，98.6％。LC/MS (m/z) 408.3 (M + ); RT = 3.89, (UV, ELSD) 91.1%, 98.6%.

1ar[2-三氟甲基-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸丙酯。1ar [2-Trifluoromethyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamate propyl ester.

LC/MS(m/z)421.1([M+H]+)；RT＝3.52，(UV，ELSD)99.2％，99.8％。LC/MS (m/z) 421.1 ([M+H] + ); RT = 3.52, (UV, ELSD) 99.2%, 99.8%.

1as[4-(4-二甲基氨基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸丙酯。1as [4-(4-Dimethylamino-benzylamino)-2-trifluoromethyl-phenyl]-carbamic acid propyl ester.

LC/MS(m/z)394.3([M-1]+)；RT＝2.02，(UV，ELSD)63.4％，100.0％。LC/MS (m/z) 394.3 ([M-1] + ); RT = 2.02, (UV, ELSD) 63.4%, 100.0%.

1at[4-(4-甲基硫烷基-苄基氨基)-2-三氟甲基-苯基]-氨基甲酸丙酯。1at[4-(4-Methylsulfanyl-benzylamino)-2-trifluoromethyl-phenyl]-carbamic acid propyl ester.

LC/MS(m/z)398.1(M+)；RT＝3.40，(UV，ELSD)92.5％，98.1％。LC/MS (m/z) 398.1 (M + ); RT = 3.40, (UV, ELSD) 92.5%, 98.1%.

1au{4-[(4-溴-噻吩-2-基甲基)-氨基]-2-氰基苯基}-氨基甲酸丙酯。1 au {4-[(4-Bromo-thiophen-2-ylmethyl)-amino]-2-cyanophenyl}-carbamic acid propyl ester.

LC/MS(m/z)394.0([M+H]+)；RT＝3.15，(UV，ELSD)97.5％，89.8％。LC/MS (m/z) 394.0 ([M+H] + ); RT = 3.15, (UV, ELSD) 97.5%, 89.8%.

1av{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-氰基苯基}-氨基甲酸丙酯。1 av {4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-cyanophenyl}-carbamate propyl ester.

LC/MS(m/z)348.9(M+)；RT＝3.11，(UV，ELSD)99.7％，96.3％。LC/MS (m/z) 348.9 (M + ); RT = 3.11, (UV, ELSD) 99.7%, 96.3%.

1aw[2-氰基-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸丙酯。1aw [2-cyano-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamate propyl ester.

LC/MS(m/z)378.3([M+H]+)；RT＝3.25，(UV，ELSD)99.6％，99.7％。LC/MS (m/z) 378.3 ([M+H] + ); RT = 3.25, (UV, ELSD) 99.6%, 99.7%.

1ax{2-溴-4-[(5-溴-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯。1 ax{2-Bromo-4-[(5-bromo-thiophen-2-ylmethyl)-amino]-phenyl}-carbamate propyl ester.

LC/MS(m/z)447.9([M+H]+)；RT＝3.48，(UV，ELSD)99.3％，99.3％。LC/MS (m/z) 447.9 ([M+H] + ); RT = 3.48, (UV, ELSD) 99.3%, 99.3%.

1ay{2-溴-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯。1ay{2-Bromo-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-carbamate propyl ester.

LC/MS(m/z)402.9([M+H]+)；RT＝3.47，(UV，ELSD)95.7％，99.6％。LC/MS (m/z) 402.9 ([M+H] + ); RT = 3.47, (UV, ELSD) 95.7%, 99.6%.

1az[2-溴-4-(4-异丙基苄基氨基)-苯基]-氨基甲酸丙酯。1az[2-Bromo-4-(4-isopropylbenzylamino)-phenyl]-carbamate propyl ester.

LC/MS(m/z)406.1([M+H]+)；RT＝3.72，(UV，ELSD)80.2％，93.9％。LC/MS (m/z) 406.1 ([M+H] + ); RT = 3.72, (UV, ELSD) 80.2%, 93.9%.

1ba[2-溴-4-(4-叔-丁基-苄基氨基)-苯基]-氨基甲酸丙酯。1ba[2-Bromo-4-(4-tert-butyl-benzylamino)-phenyl]-carbamate propyl ester.

LC/MS(m/z)418.2(M+)；RT＝3.86，(UV，ELSD)87.2％，96.8％。LC/MS (m/z) 418.2 (M + ); RT = 3.86, (UV, ELSD) 87.2%, 96.8%.

1bb[2-溴-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸丙酯。1bb[2-Bromo-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamate propyl ester.

LC/MS(m/z)431.0([M+H]+)；RT＝3.55，(UV，ELSD)95.9％，99.8％。LC/MS (m/z) 431.0 ([M+H] + ); RT = 3.55, (UV, ELSD) 95.9%, 99.8%.

1bc[2-溴-4-(4-甲基硫烷基-苄基氨基)-苯基]-氨基甲酸丙酯。1bc[2-Bromo-4-(4-methylsulfanyl-benzylamino)-phenyl]-carbamate propyl ester.

LC/MS(m/z)409.0([M+H]+)；RT＝3.36，(UV，ELSD)98.4％，99.7％。LC/MS (m/z) 409.0 ([M+H] + ); RT = 3.36, (UV, ELSD) 98.4%, 99.7%.

1bd N-{4-[(5-溴-噻吩-2-基甲基)-氨基]-2-甲氧基苯基}-丁酰胺。1bd N-{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-butanamide.

LC/MS(m/z)382.0(M+)；RT＝2.66，(UV，ELSD)95.9％，99.3％。LC/MS (m/z) 382.0 (M + ); RT = 2.66, (UV, ELSD) 95.9%, 99.3%.

1be N-{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-甲氧基苯基}-丁酰胺。1be N-{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-butanamide.

LC/MS(m/z)339.2([M+H]+)；RT＝2.61，(UV，ELSD)96.4％，98.4％。LC/MS (m/z) 339.2 ([M+H] + ); RT = 2.61, (UV, ELSD) 96.4%, 98.4%.

1bf N-[4-(4-异丙基苄基氨基)-2-甲氧基苯基]-丁酰胺.1bf N-[4-(4-isopropylbenzylamino)-2-methoxyphenyl]-butanamide.

LC/MS(m/z)341.1([M+H]+)；RT＝2.49，(UV，ELSD)91.1％，100.0％。LC/MS (m/z) 341.1 ([M+H] + ); RT = 2.49, (UV, ELSD) 91.1%, 100.0%.

1bg N-[4-(4-叔-丁基-苄基氨基)-2-甲氧基苯基]-丁酰胺。1bg N-[4-(4-tert-butyl-benzylamino)-2-methoxyphenyl]-butanamide.

LC/MS(m/z)355.2([M+H]+)；RT＝2.65，(UV，ELSD)97.0％，100.0％。LC/MS (m/z) 355.2 ([M+H] + ); RT = 2.65, (UV, ELSD) 97.0%, 100.0%.

1bh N-[2-甲氧基-4-(4-三氟甲基-苄基氨基)-苯基]-丁酰胺。1bh N-[2-Methoxy-4-(4-trifluoromethyl-benzylamino)-phenyl]-butanamide.

LC/MS(m/z)367.2([M+H]+)；RT＝2.79，(UV，ELSD)93.9％，96.6％。LC/MS (m/z) 367.2 ([M+H] + ); RT = 2.79, (UV, ELSD) 93.9%, 96.6%.

1bi{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-呋喃-2-基-苯基}-氨基甲酸丙酯。1bi {4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-furan-2-yl-phenyl}-carbamate propyl ester.

LC/MS(m/z)390.1(M+)；RT＝3.38，(UV，ELSD)92.9％，99.8％。LC/MS (m/z) 390.1 (M + ); RT = 3.38, (UV, ELSD) 92.9%, 99.8%.

1bj[2-呋喃-2-基-4-(4-异丙基苄基氨基)-苯基]-氨基甲酸丙酯。1bj [2-furan-2-yl-4-(4-isopropylbenzylamino)-phenyl]-carbamate propyl ester.

LC/MS(m/z)393.2([M+H]+)；RT＝3.41，(UV，ELSD)89.9％，100.0％。LC/MS (m/z) 393.2 ([M+H] + ); RT = 3.41, (UV, ELSD) 89.9%, 100.0%.

1bk[5-(4-氟苄基氨基)-联苯-2-基]-氨基甲酸丙酯。1bk [5-(4-Fluorobenzylamino)-biphenyl-2-yl]-propyl carbamate.

LC/MS(m/z)379.3([M+H]+)；RT＝3.06，(UV，ELSD)83.7％，99.7％。LC/MS (m/z) 379.3 ([M+H] + ); RT = 3.06, (UV, ELSD) 83.7%, 99.7%.

1bl{5-[(5-氯-噻吩-2-基甲基)-氨基]-联苯-2-基}-氨基甲酸丙酯。1bl{5-[(5-Chloro-thiophen-2-ylmethyl)-amino]-biphenyl-2-yl}-carbamate propyl ester.

LC/MS(m/z)400.0(M+)；RT＝3.48，(UV，ELSD)89.8％，98.7％。LC/MS (m/z) 400.0 (M + ); RT = 3.48, (UV, ELSD) 89.8%, 98.7%.

1bm[5-(4-异丙基苄基氨基)-联苯-2-基]-氨基甲酸丙酯。1bm [5-(4-Isopropylbenzylamino)-biphenyl-2-yl]-carbamate propyl ester.

LC/MS(m/z)403.2([M+H]+)；RT＝3.37，(UV，ELSD)73.8％，98.7％。LC/MS (m/z) 403.2 ([M+H] + ); RT = 3.37, (UV, ELSD) 73.8%, 98.7%.

1zz N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2，2，2-三氟乙酰胺。1zz N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2,2,2-trifluoroacetamide.

在上面通式XIII-XXIII的中间体的合成中报告了这种化合物的数据。Data for this compound are reported above in the synthesis of intermediates of general formulas XIII-XXIII.

实施例2Example 2

2a{4-[(4-氟-苄基)-(甲基)氨基]-2-甲氧基苯基}-氨基甲酸丙酯。2a {4-[(4-Fluoro-benzyl)-(methyl)amino]-2-methoxyphenyl}-carbamic acid propyl ester.

将(4-氨基-2-甲氧基苯基)-氨基甲酸丙酯(0.3mL，0.1M四氢呋喃(THF)溶液)和4-氟苯甲醛(0.3mL，0.1M四氢呋喃(THF)溶液)的混合物加热至50℃加热60分钟并将其真空蒸发。向所得的残余物中加入氰基硼氢化钠(NaBH3CN)(0.6mL，0.2M甲醇溶液)和醋酸(0.03mL)。将该反应混合物在室温下保持30分钟，然后向其中加入甲醛(0.03mL，37％水溶液)和醋酸(0.03mL)。在30分钟后，将该反应混合物真空蒸发。用制备LC/MS对该标题化合物进行分离，得到4.3mg无色固体，收率为41％。1H NMR(1∶4DMSO-H6/DMSO-D6)：8.04(br.s，NH)，7.25(m，2H)，7.13(m，3H)，6.36(s，1H)，6.24(d，1H)，4.53(s，2H，CH2)，3.93(t，2H)，3.70(s，3H，OMe)，2.97(s，NMe)，1.57(m，2H)，0.89(t，3H)。LC/MS(m/z)347.2([M+H]+)；RT＝2.32，(UV，ELSD)96％，100％。A solution of (4-amino-2-methoxyphenyl)-propyl carbamate (0.3 mL, 0.1 M solution in tetrahydrofuran (THF)) and 4-fluorobenzaldehyde (0.3 mL, 0.1 M solution in tetrahydrofuran (THF)) The mixture was heated to 50°C for 60 minutes and evaporated in vacuo. To the resulting residue were added sodium cyanoborohydride ( NaBH3CN ) (0.6 mL, 0.2M in methanol) and acetic acid (0.03 mL). The reaction mixture was kept at room temperature for 30 minutes, then formaldehyde (0.03 mL, 37% in water) and acetic acid (0.03 mL) were added thereto. After 30 minutes, the reaction mixture was evaporated in vacuo. The title compound was isolated by preparative LC/MS to give 4.3 mg of a colorless solid, 41% yield. 1 H NMR (1:4DMSO-H 6 /DMSO-D 6 ): 8.04 (br.s, NH), 7.25 (m, 2H), 7.13 (m, 3H), 6.36 (s, 1H), 6.24 (d , 1H), 4.53(s, 2H, CH 2 ), 3.93(t, 2H), 3.70(s, 3H, OMe), 2.97(s, NMe), 1.57(m, 2H), 0.89(t, 3H) . LC/MS (m/z) 347.2 ([M+H] + ); RT = 2.32, (UV, ELSD) 96%, 100%.

相似地由适宜的苯胺和醛制备下面的化合物：The following compounds were similarly prepared from the appropriate aniline and aldehyde:

2b[4-(苯并[b]噻吩-2-基甲基-(甲基)氨基)-2-甲氧基-苯基]-氨基甲酸丙酯2b[4-(Benzo[b]thiophen-2-ylmethyl-(methyl)amino)-2-methoxy-phenyl]-carbamic acid propyl ester

1H NMR(1∶4DMSO-H6/DMSO-D6)：8.07(br.s，NH)，7.86(d，1H)，7.76(d，1H)，7.30(m，4H)，6.49(s，1H)，6.36(d，1H)，4.83(s，2H，CH2)，3.94(t，2H)，3.75(s，3H，OMe)，2.98(s，NMe)，1.58(m，2H)，0.89(t，3H))。LC/MS(m/z)385.0([M+H]+)；RT＝3.25，(UV，ELSD)99％，100％。 1 H NMR (1:4DMSO-H 6 /DMSO-D 6 ): 8.07 (br.s, NH), 7.86 (d, 1H), 7.76 (d, 1H), 7.30 (m, 4H), 6.49 (s , 1H), 6.36(d, 1H), 4.83(s, 2H, CH 2 ), 3.94(t, 2H), 3.75(s, 3H, OMe), 2.98(s, NMe), 1.58(m, 2H) , 0.89(t,3H)). LC/MS (m/z) 385.0 ([M+H] + ); RT = 3.25, (UV, ELSD) 99%, 100%.

2c{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲氧基-苯基}-氨基甲酸丙酯。2c {4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methoxy-phenyl}-carbamate propyl ester.

LC/MS(m/z)367.9(M+)；RT＝3.07，(UV，ELSD)99％，100％。LC/MS (m/z) 367.9 (M + ); RT = 3.07, (UV, ELSD) 99%, 100%.

2d{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-甲氧基-苯基}-氨基甲酸丙酯。2d {4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-methoxy-phenyl}-carbamate propyl ester.

LC/MS(m/z)412.1(M+)；RT＝3.12，(UV，ELSD)99％，100％。LC/MS (m/z) 412.1 (M + ); RT = 3.12, (UV, ELSD) 99%, 100%.

2e{2-甲氧基-4-[甲基-(5-甲基-噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸丙酯。2e {2-Methoxy-4-[methyl-(5-methyl-thiophen-2-ylmethyl)-amino]-phenyl}-carbamate propyl ester.

LC/MS(m/z)348.0(M+)；RT＝2.46，(UV，ELSD)95％，100％。LC/MS (m/z) 348.0 (M + ); RT = 2.46, (UV, ELSD) 95%, 100%.

2f{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-氨基甲酸丙酯。2f {4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-carbamic acid propyl ester.

LC/MS(m/z)398.0([M+2]+)；RT＝3.10，(UV，ELSD)97.0％，98.1％。LC/MS (m/z) 398.0 ([M+2] + ); RT = 3.10, (UV, ELSD) 97.0%, 98.1%.

2g{4-[(4-异丙基苄基)-(甲基)氨基]-2-甲基苯基}-氨基甲酸丙酯。2 g of propyl {4-[(4-isopropylbenzyl)-(methyl)amino]-2-methylphenyl}-carbamate.

LC/MS(m/z)355.2([M+H]+)；RT＝2.70，(UV，ELSD)85.4％，99.5％。LC/MS (m/z) 355.2 ([M+H] + ); RT = 2.70, (UV, ELSD) 85.4%, 99.5%.

2h{2-甲基-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸丙酯。2h {2-Methyl-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-carbamate propyl ester.

LC/MS(m/z)380.3(M+)；RT＝3.18，(UV，ELSD)95.2％，98.5％。LC/MS (m/z) 380.3 (M + ); RT = 3.18, (UV, ELSD) 95.2%, 98.5%.

2i{2-甲基-4-[甲基-(4-甲基硫烷基-苄基)-氨基]-苯基}-氨基甲酸丙酯。2i{2-Methyl-4-[methyl-(4-methylsulfanyl-benzyl)-amino]-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)358.0(M+)；RT＝2.42，(UV，ELSD)97.9％，99.0％。LC/MS (m/z) 358.0 (M + ); RT = 2.42, (UV, ELSD) 97.9%, 99.0%.

2j{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-氯苯基}-氨基甲酸乙酯。2j {4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-chlorophenyl}-carbamate ethyl ester.

LC/MS(m/z)374.9([M+H]+)；RT＝3.92，(UV，ELSD)97.8％，100.0％。LC/MS (m/z) 374.9 ([M+H] + ); RT = 3.92, (UV, ELSD) 97.8%, 100.0%.

2k{2-氯-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸乙酯。2k {2-Chloro-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-carbamate ethyl ester.

LC/MS(m/z)387.3([M+H]+)；RT＝3.59，(UV，ELSD)99.9％，100.0％。LC/MS (m/z) 387.3 ([M+H] + ); RT = 3.59, (UV, ELSD) 99.9%, 100.0%.

2l{2-氯-4-[甲基-(4-甲基硫烷基-苄基)-氨基]-苯基}-氨基甲酸乙酯。21 {2-Chloro-4-[methyl-(4-methylsulfanyl-benzyl)-amino]-phenyl}-urethane ethyl ester.

LC/MS(m/z)363.1([M-1]+)；RT＝3.36，(UV，ELSD)92.1％，99.6％。LC/MS (m/z) 363.1 ([M-1] + ); RT = 3.36, (UV, ELSD) 92.1%, 99.6%.

2m{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-氯苯基}-氨基甲酸丙酯。2m Propyl {4-[(5-bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-chlorophenyl}-carbamate.

LC/MS(m/z)418.1([M+H]+)；RT＝3.80，(UV，ELSD)99.3％，100.0％。LC/MS (m/z) 418.1 ([M+H] + ); RT = 3.80, (UV, ELSD) 99.3%, 100.0%.

2n{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丙酯。2n{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)374.0([M+H]+)；RT＝3.77，(UV，ELSD)99.6％，99.9％。LC/MS (m/z) 374.0 ([M+H] + ); RT = 3.77, (UV, ELSD) 99.6%, 99.9%.

2o{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-氯苯基}-氨基甲酸丙酯。2o{4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-chlorophenyl}-carbamic acid propyl ester.

LC/MS(m/z)389.2([M+H]+)；RT＝4.09，(UV，ELSD)99.6％，99.9％。LC/MS (m/z) 389.2 ([M+H] + ); RT = 4.09, (UV, ELSD) 99.6%, 99.9%.

2p{2-氯-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸丙酯。2p{2-Chloro-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-carbamate propyl ester.

LC/MS(m/z)401.1([M+H]+)；RT＝3.81，(UV，ELSD)99.8％，100.0％。LC/MS (m/z) 401.1 ([M+H] + ); RT = 3.81, (UV, ELSD) 99.8%, 100.0%.

2q{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯。2q {4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-urethane ethyl ester.

LC/MS(m/z)435.9([M-1]+)；RT＝3.56，(UV，ELSD)99.4％，100.0％。LC/MS (m/z) 435.9 ([M-1] + ); RT = 3.56, (UV, ELSD) 99.4%, 100.0%.

2r{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-三氟甲基-苯基}氨基甲酸乙酯。2r{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}carbamate ethyl ester.

LC/MS(m/z)392.3(M+)；RT＝3.56，(UV，ELSD)99.0％，100.0％。LC/MS (m/z) 392.3 (M + ); RT = 3.56, (UV, ELSD) 99.0%, 100.0%.

2s{4(4-异丙基-苄基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯。2s{4(4-Isopropyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamate ethyl ester.

LC/MS(m/z)395.3([M+H]+)；RT＝3.85，(UV，ELSD)99.0％，100.0％。LC/MS (m/z) 395.3 ([M+H] + ); RT = 3.85, (UV, ELSD) 99.0%, 100.0%.

2t{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯.2t{4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamate ethyl ester.

LC/MS(m/z)409.2([M+H]+)；RT＝3.98，(UV，ELSD)97.9％，99.8％。LC/MS (m/z) 409.2 ([M+H] + ); RT = 3.98, (UV, ELSD) 97.9%, 99.8%.

2u{4-[甲基-(4-三氟甲基-苄基)-氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯。2u{4-[Methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-carbamate ethyl ester.

LC/MS(m/z)421.2([M+H]+)；RT＝3.59，(UV，ELSD)92.9％，98.5％。LC/MS (m/z) 421.2 ([M+H] + ); RT = 3.59, (UV, ELSD) 92.9%, 98.5%.

2v{4-[甲基-(4-三氟甲基-苄基)-氨基]-2-三氟甲基-苯基}-氨基甲酸乙酯。2v Ethyl {4-[methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-carbamate.

LC/MS(m/z)397.0([M-1]+)；RT＝3.48，(UV，ELSD)99.4％，99.9％。LC/MS (m/z) 397.0 ([M-1] + ); RT = 3.48, (UV, ELSD) 99.4%, 99.9%.

2w{4-[(5-溴-噻吩-2-基甲基)-甲基-氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯。2w Propyl {4-[(5-bromo-thiophen-2-ylmethyl)-methyl-amino]-2-trifluoromethyl-phenyl}-carbamate.

LC/MS(m/z)449.9([M-1]+)；RT＝3.76，(UV，ELSD)99.5％，100.0％。LC/MS (m/z) 449.9 ([M-1] + ); RT = 3.76, (UV, ELSD) 99.5%, 100.0%.

2x{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯。2x {4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamate propyl ester.

LC/MS(m/z)405.9(M+)；RT＝3.73，(UV，ELSD)98.4％，100.0％。LC/MS (m/z) 405.9 (M + ); RT = 3.73, (UV, ELSD) 98.4%, 100.0%.

2y{4-[(4-异丙基-苄基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯。2y {4-[(4-Isopropyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)409.2([M+H]+)；RT＝4.04，(UV，ELSD)99.3％，99.9％。LC/MS (m/z) 409.2 ([M+H] + ); RT = 4.04, (UV, ELSD) 99.3%, 99.9%.

2z{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯。2z {4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamate propyl ester.

LC/MS(m/z)423.1([M+H]+)；RT＝4.29，(UV，ELSD)98.9％，99.7％。LC/MS (m/z) 423.1 ([M+H] + ); RT = 4.29, (UV, ELSD) 98.9%, 99.7%.

2aa{4-[甲基-(4-三氟甲基-苄基)-氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯。2aa {4-[Methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)435.3([M+H]+)；RT＝3.77，(UV，ELSD)99.7％，99.9％。LC/MS (m/z) 435.3 ([M+H] + ); RT = 3.77, (UV, ELSD) 99.7%, 99.9%.

2ab{4-[甲基-(4-三氟甲基-苄基)-氨基]-2-三氟甲基-苯基}-氨基甲酸丙酯。2ab{4-[Methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)412.0(M+)；RT＝3.67，(UV，ELSD)99.3％，99.8％。LC/MS (m/z) 412.0 (M + ); RT = 3.67, (UV, ELSD) 99.3%, 99.8%.

2ac{4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-2-氰基苯基}-氨基甲酸丙酯。2ac {4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-cyanophenyl}-carbamic acid propyl ester.

LC/MS(m/z)407.0(M+)；RT＝3.39，(UV，ELSD)97.7％，99.6％。LC/MS (m/z) 407.0 (M + ); RT = 3.39, (UV, ELSD) 97.7%, 99.6%.

2ad{4-[(4-叔-丁基-苄基)-(甲基)氨基]-2-氰基苯基}-氨基甲酸丙酯。2ad {4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-cyanophenyl}-carbamate propyl ester.

LC/MS(m/z)380.3([M+H]+)；RT＝3.83，(UV，ELSD)99.4％，99.9％。LC/MS (m/z) 380.3 ([M+H] + ); RT = 3.83, (UV, ELSD) 99.4%, 99.9%.

2ae{2-氰基-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸丙酯。2ae {2-Cyano-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)392.3([M+H]+)；RT＝3.44，(UV，ELSD)98.9％，99.9％。LC/MS (m/z) 392.3 ([M+H] + ); RT = 3.44, (UV, ELSD) 98.9%, 99.9%.

2af{2-溴-4-[(5-溴-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丙酯。2af {2-Bromo-4-[(5-bromo-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)462.1([M+H]+)；RT＝3.84，(UV，ELSD)98.2％，99.9％。LC/MS (m/z) 462.1 ([M+H] + ); RT = 3.84, (UV, ELSD) 98.2%, 99.9%.

2ag{2-溴-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丙酯。LC/MS(m/z)418.1([M+H]+)；RT＝3.83，(UV，ELSD)99.3％，100.0％。2ag {2-Bromo-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester. LC/MS (m/z) 418.1 ([M+H] + ); RT = 3.83, (UV, ELSD) 99.3%, 100.0%.

2ah{2-溴-4-[(4-异丙基苄基)-(甲基)氨基]-苯基}-氨基甲酸丙酯。2ah {2-Bromo-4-[(4-isopropylbenzyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)420.2([M+H]+)；RT＝4.04，(UV，ELSD)98.8％，99.7％。LC/MS (m/z) 420.2 ([M+H] + ); RT = 4.04, (UV, ELSD) 98.8%, 99.7%.

2ai{2-溴-4-[(4-叔-丁基-苄基)-(甲基)氨基]-苯基}-氨基甲酸丙酯。2ai{2-Bromo-4-[(4-tert-butyl-benzyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)432.1(M+)；RT＝4.15，(UV，ELSD)99.3％，100.0％。LC/MS (m/z) 432.1 (M + ); RT = 4.15, (UV, ELSD) 99.3%, 100.0%.

2aj{2-溴-4-[甲基-(4-三氟甲基-苄基)-氨基]-苯基}-氨基甲酸丙酯。2aj {2-Bromo-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-carbamic acid propyl ester.

LC/MS(m/z)447.0([M+H]+)；RT＝3.84，(UV，ELSD)98.4％，99.9％。LC/MS (m/z) 447.0 ([M+H] + ); RT = 3.84, (UV, ELSD) 98.4%, 99.9%.

2zz N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2，2，2-三氟乙酰胺。2zz N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2,2,2-trifluoroacetamide.

在上面通式XIII-XXIII的中间体的合成中报告了这种化合物的数据。Data for this compound are reported above in the synthesis of intermediates of general formulas XIII-XXIII.

实施例3Example 3

3a{4-[(4-氟苄基)-(甲基)-氨基]-2-异丙氧基苯基}-氨基甲酸乙酯3a{4-[(4-fluorobenzyl)-(methyl)-amino]-2-isopropoxyphenyl}-carbamate ethyl ester

将4-(4-氟苄基)-(甲基)-氨基-2-异丙氧基苯胺(0.29g)溶解于无水二噁烷(3mL)中。向其中加入N，N-二异丙基乙基胺(0.27mL)和氯甲酸乙酯(0.15mL)并将该反应混合物在室温下搅拌一整夜。向其中加入水(5mL)并将所得的混合物用乙酸乙酯(3×10mL)进行萃取。将有机相用硫酸钠进行干燥并过滤。将溶剂真空蒸发并将粗品用闪柱色谱纯化(硅胶，用庚烷/乙酸乙酯19∶1，1％三乙胺梯度洗脱)。将溶剂真空蒸发，得到无色油状物形式的标题化合物(0.20g，55％)。LC-MS(m/z)361.3([M+H]+)；RT＝2.58，(UV，ELSD)90％，98％。4-(4-Fluorobenzyl)-(methyl)-amino-2-isopropoxyaniline (0.29 g) was dissolved in anhydrous dioxane (3 mL). N,N-Diisopropylethylamine (0.27 mL) and ethyl chloroformate (0.15 mL) were added thereto and the reaction mixture was stirred at room temperature overnight. Water (5 mL) was added thereto and the resulting mixture was extracted with ethyl acetate (3 x 10 mL). The organic phase was dried over sodium sulfate and filtered. The solvent was evaporated in vacuo and the crude product was purified by flash column chromatography (silica gel, gradient elution with heptane/ethyl acetate 19:1, 1% triethylamine). The solvent was evaporated in vacuo to give the title compound (0.20 g, 55%) as a colorless oil. LC-MS (m/z) 361.3 ([M+H] + ); RT = 2.58, (UV, ELSD) 90%, 98%.

实施例4Example 4

4a[4-(3-氟苄基氨基)-2-甲氧基苯基J-氨基甲酸乙酯4a[4-(3-fluorobenzylamino)-2-methoxyphenyl J-carbamate ethyl ester

将3-氟苯甲醛在无水甲醇(84μL，476mM)中的溶液加入到(4-氨基-2-甲氧基苯基)-氨基甲酸乙酯溶液(84μL，0.476M无水甲醇溶液)中。将所得的混合物加热至40℃加热30分钟。将溶剂真空蒸发并将剩余的材料溶解于1，2-二氯乙烷(1mL)中。向其中加入三乙酰氧基硼氢化钠(20mg)并将所得的混合物在室温下保持2小时，在这两个时期中分别进行10分钟声处理。将该反应混合物用硅胶(500mg)过滤并用1，2-二氯乙烷(3mL)对该柱进行洗涤。将溶剂真空蒸发，得到标题化合物(5.7mg，45％)。Add a solution of 3-fluorobenzaldehyde in anhydrous methanol (84 μL, 476 mM) to a solution of (4-amino-2-methoxyphenyl)-urethane (84 μL, 0.476 M in anhydrous methanol) . The resulting mixture was heated to 40°C for 30 minutes. The solvent was evaporated in vacuo and the remaining material was dissolved in 1,2-dichloroethane (1 mL). To this was added sodium triacetoxyborohydride (20 mg) and the resulting mixture was maintained at room temperature for 2 hours, with 10 minutes of sonication during each period. The reaction mixture was filtered through silica gel (500 mg) and the cartridge was washed with 1,2-dichloroethane (3 mL). The solvent was evaporated in vacuo to give the title compound (5.7 mg, 45%).

LC-MS(m/z)318.1(M+)；RT＝2.33，(UV，ELSD)93％，100％。LC-MS (m/z) 318.1 (M + ); RT = 2.33, (UV, ELSD) 93%, 100%.

用相似的方式制备下面的化合物：The following compounds were prepared in a similar manner:

4b[4-(4-异丙基苄基氨基)-2-甲氧基苯基]-氨基甲酸乙酯4b[4-(4-isopropylbenzylamino)-2-methoxyphenyl]-ethyl carbamate

LC-MS(m/z)341.3([M-1]+)；RT＝2.51，(UV，ELSD)86％，100％。LC-MS (m/z) 341.3 ([M-1] + ); RT = 2.51, (UV, ELSD) 86%, 100%.

4c{2-甲氧基-4-[(3-甲基噻吩-2-基甲基)-氨基]-苯基}-氨基甲酸乙酯4c{2-Methoxy-4-[(3-methylthiophen-2-ylmethyl)-amino]-phenyl}-urethane

LC-MS(m/z)319.9(M+)；RT＝2.10，(UV，ELSD)79％，99％。LC-MS (m/z) 319.9 (M + ); RT = 2.10, (UV, ELSD) 79%, 99%.

4d[4-(2，4-二氟苄基氨基)-2-甲氧基苯基]-氨基甲酸乙酯4d[4-(2,4-difluorobenzylamino)-2-methoxyphenyl]-urethane

LC-MS(m/z)337.2([M+H]+)；RT＝2.44，(UV，ELSD)93％，100％。LC-MS (m/z) 337.2 ([M+H] + ); RT = 2.44, (UV, ELSD) 93%, 100%.

实施例5Example 5

5a[2-环戊氧基-4-(4-甲氧基苄基氨基)-苯基]氨基甲酸乙酯5a[2-Cyclopentyloxy-4-(4-methoxybenzylamino)-phenyl]urethane

将(2-环戊氧基-4-硝基苯基)-氨基甲酸乙酯(294mg)溶解于乙醇(26mL)中。向其中加入锌颗粒(1.63g)和水性盐酸(5.0mL，2M)。将所得的混合物在室温下声处理6.5小时，然后将其在室温下放置一整夜。向其中加入饱和碳酸氢钠水溶液(100mL)并将该混合物用乙酸乙酯进行萃取(2×100mL)。将有机相用水(100mL)和盐水(100mL)进行洗涤，用硫酸镁干燥，并将其真空蒸发。将所得的油状物溶解于甲醇(1.82mL)中，并将这种溶液的等分试样(40μL)与4-甲氧基苯甲醛(40μL，0.466M甲醇溶液)混合。将所得的混合物加热至40℃加热20分钟。将溶剂真空蒸发，并将剩余的材料溶解于1，2-二氯乙烷(1mL)中。向其中加入三乙酰氧基硼氢化钠(20mg)并将所得的混合物在室温下放置2小时，在这两个时期中分别进行10分钟声处理。将该反应混合物用硅胶(500mg)过滤，并用1，2-二氯乙烷(3mL)对该柱进行洗涤。将溶剂真空蒸发，得到标题化合物(6.0mg，84％得自醛)。Ethyl (2-cyclopentyloxy-4-nitrophenyl)-carbamate (294 mg) was dissolved in ethanol (26 mL). To this was added zinc particles (1.63 g) and aqueous hydrochloric acid (5.0 mL, 2M). The resulting mixture was sonicated at room temperature for 6.5 hours and then left overnight at room temperature. To this was added saturated aqueous sodium bicarbonate (100 mL) and the mixture was extracted with ethyl acetate (2 x 100 mL). The organic phase was washed with water (100 mL) and brine (100 mL), dried over magnesium sulfate and evaporated in vacuo. The resulting oil was dissolved in methanol (1.82 mL), and an aliquot (40 μL) of this solution was mixed with 4-methoxybenzaldehyde (40 μL, 0.466M in methanol). The resulting mixture was heated to 40°C for 20 minutes. The solvent was evaporated in vacuo, and the remaining material was dissolved in 1,2-dichloroethane (1 mL). To this was added sodium triacetoxyborohydride (20 mg) and the resulting mixture was left at room temperature for 2 hours with 10 minutes of sonication during each period. The reaction mixture was filtered through silica gel (500 mg), and the cartridge was washed with 1,2-dichloroethane (3 mL). The solvent was evaporated in vacuo to give the title compound (6.0 mg, 84% from aldehyde).

LC-MS(m/z)384.1(M+)；RT＝2.40，(UV，ELSD)76％，96％。LC-MS (m/z) 384.1 (M + ); RT = 2.40, (UV, ELSD) 76%, 96%.

用相似的方式制备下面的化合物：The following compounds were prepared in a similar manner:

5b[2-环戊氧基-4-(3-氟-2-甲基苄基氨基)-苯基]-氨基甲酸乙酯5b[2-cyclopentyloxy-4-(3-fluoro-2-methylbenzylamino)-phenyl]-urethane

将该产物用制备LC-MS纯化。The product was purified by preparative LC-MS.

LC-MS(m/z)386.2(M+)；RT＝3.22，(UV，ELSD)80％，91％。LC-MS (m/z) 386.2 (M + ); RT = 3.22, (UV, ELSD) 80%, 91%.

5c[4-(3-氟-2-甲基苄基氨基)-2-苯乙氧基苯基]-氨基甲酸乙酯5c[4-(3-Fluoro-2-methylbenzylamino)-2-phenethoxyphenyl]-carbamate ethyl ester

将该产物用制备LC-MS纯化。The product was purified by preparative LC-MS.

LC-MS(in/z)422.3(M+)；RT＝3.38，(UV，ELSD)84％，91％。LC-MS (in/z) 422.3 (M + ); RT = 3.38, (UV, ELSD) 84%, 91%.

5d[2-苄氧基-4-(3-氟-2-甲基苄基氨基)-苯基]-氨基甲酸乙酯5d[2-Benzyloxy-4-(3-fluoro-2-methylbenzylamino)-phenyl]-carbamate ethyl ester

将该产物用制备LC-MS纯化。The product was purified by preparative LC-MS.

LC-MS(m/z)409.2([M+H]+)；RT＝3.30，(UV，ELSD)80％，89％。LC-MS (m/z) 409.2 ([M+H] + ); RT = 3.30, (UV, ELSD) 80%, 89%.

5e[2-苄氧基-4-(4-甲基硫烷基苄基氨基)-苯基]-氨基甲酸乙酯5e[2-Benzyloxy-4-(4-methylsulfanylbenzylamino)-phenyl]-urethane

LC-MS(m/z)422.1(M+)；RT＝2.92，(UV，ELSD)83％，89％。LC-MS (m/z) 422.1 (M + ); RT = 2.92, (UV, ELSD) 83%, 89%.

5f{4-[(苯并[b]噻吩-3-基甲基)-氨基]-2-环戊氧基苯基}-氨基甲酸乙酯5f{4-[(Benzo[b]thiophen-3-ylmethyl)-amino]-2-cyclopentyloxyphenyl}-urethane

将该产物用制备LC-MS纯化。The product was purified by preparative LC-MS.

LC-MS(m/z)411.1([M+H]+)；RT＝3.12，(UV，ELSD)79％，85％。LC-MS (m/z) 411.1 ([M+H] + ); RT = 3.12, (UV, ELSD) 79%, 85%.

5g[4-(3-氟-2-甲基苄基氨基)-2-异丙氧基苯基]-氨基甲酸乙酯5g [4-(3-fluoro-2-methylbenzylamino)-2-isopropoxyphenyl]-carbamate ethyl ester

将该产物用制备LC-MS纯化。The product was purified by preparative LC-MS.

LC-MS(m/z)361.2([M+H]+)；RT＝2.95，(UV，ELSD)77％，86％。LC-MS (m/z) 361.2 ([M+H]+); RT = 2.95, (UV, ELSD) 77%, 86%.

5h[2-苄氧基-4-(3-甲氧基苄基氨基)-苯基]-氨基甲酸乙酯5h[2-Benzyloxy-4-(3-methoxybenzylamino)-phenyl]-urethane

LC-MS(m/z)407.3([M+H]+)RT＝2.81，(UV，ELSD)76％，87％。LC-MS (m/z) 407.3 ([M+H] + ) RT = 2.81, (UV, ELSD) 76%, 87%.

5i{4-[(苯并[1，3]间二氧杂环戊烯-5-基甲基)-氨基]-2-异丙氧基苯基}-氨基甲酸乙酯5i{4-[(Benzo[1,3]dioxol-5-ylmethyl)-amino]-2-isopropoxyphenyl}-urethane

LC-MS(m/z)372.1(M+)；RT＝2.24，(UV，ELSD)76％，86％。LC-MS (m/z) 372.1 (M + ); RT = 2.24, (UV, ELSD) 76%, 86%.

实施例6Example 6

6o N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-3-环己基丙酰胺。6o N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-cyclohexylpropionamide.

方法A：向2-氯-N(4)-(5-氯-噻吩-2-基甲基)-N(4)-甲基-苯-1，4-二胺(14mg)和三乙胺(0.04mL)在乙腈(1mL)中的混合物中加入3-环己基-丙酰(proionyl)氯(0.03mL)。真空蒸发掉挥发性物质并用制备LC-MS对标题化合物进行分离。Method A: Addition of 2-chloro-N(4)-(5-chloro-thiophen-2-ylmethyl)-N(4)-methyl-benzene-1,4-diamine (14 mg) and triethylamine (0.04 mL) in acetonitrile (1 mL) was added 3-cyclohexyl-proionyl chloride (0.03 mL). The volatiles were evaporated in vacuo and the title compound was isolated by preparative LC-MS.

方法B：向2-氯-N(4)-(5-氯-噻吩-2-基甲基)-N(4)-甲基-苯-1，4-二胺(470mg，1.64mmol)和碳酸氢钠在乙腈(40mL)中的化合物中加入3-环己基-丙酰(proionyl)氯(372mg，2.13mmol)。在1小时后，将该反应混合物用水(100mL)和冰淬熄。通过过滤分离出灰色-褐色固体形式的标题化合物。收率为0.422g，60％。Method B: To 2-chloro-N(4)-(5-chloro-thiophen-2-ylmethyl)-N(4)-methyl-benzene-1,4-diamine (470mg, 1.64mmol) and Sodium bicarbonate in acetonitrile (40 mL) was added 3-cyclohexyl-proionyl chloride (372 mg, 2.13 mmol). After 1 hour, the reaction mixture was quenched with water (100 mL) and ice. The title compound was isolated by filtration as a gray-brown solid. Yield 0.422g, 60%.

LC/MS(m/z)425.4([M+H]+)；RT＝4.09，(UV，ELSD)97％，100％。1HNMR(DMSO-d6)：0.87(m，2H)，1.05-1.29(m，4H)，1.47(q，2H)，1.56-1.76(m，5H)，2.29(t，2H)，2.91(s，3H)，4.67(s，2H)，6.76(dd，1H)，6.83(d，1H)，6.88(d，1H)，6.96(d，1H)，7.27(d，1H)。LC/MS (m/z) 425.4 ([M+H] + ); RT = 4.09, (UV, ELSD) 97%, 100%. 1 HNMR (DMSO-d 6 ): 0.87 (m, 2H), 1.05-1.29 (m, 4H), 1.47 (q, 2H), 1.56-1.76 (m, 5H), 2.29 (t, 2H), 2.91 ( s, 3H), 4.67 (s, 2H), 6.76 (dd, 1H), 6.83 (d, 1H), 6.88 (d, 1H), 6.96 (d, 1H), 7.27 (d, 1H).

用方法A由相应的苯胺和适宜的酰基氯、氯甲酸酯、氨基甲酰氯、异氰酸酯、或重碳酸二-叔-丁酯(Boc2O)相似地制备下面的化合物。在酰基氯的情况中用三乙胺作为碱。在氯甲酸酯和氨基甲酰氯的情况中用吡啶作为碱。在异氰酸酯和Boc2O的情况中不使用碱。在用(4-氨基-3-氯苯基)-(5-氯-噻吩-2-基甲基)-氨基甲酸叔-丁酯作为苯胺的情况中，在蒸发后将残余物用2％苯甲醚在三氟醋酸和二氯甲烷1∶1的混合物中的溶液处理1小时并再次对其进行蒸发，然后用制备LC-MS进行处理：The following compounds were similarly prepared by Method A from the corresponding aniline and the appropriate acid chloride, chloroformate, carbamoyl chloride, isocyanate, or di-tert-butyl dicarbonate ( Boc2O ). In the case of acid chlorides triethylamine is used as base. In the case of chloroformates and carbamoyl chlorides pyridine is used as base. In the case of isocyanate and Boc2O no base is used. In the case of (4-amino-3-chlorophenyl)-(5-chloro-thiophen-2-ylmethyl)-carbamic acid tert-butyl ester as aniline, the residue was washed with 2% benzene after evaporation. A solution of methyl ether in a 1:1 mixture of trifluoroacetic acid and dichloromethane was treated for 1 h and evaporated again, then processed by preparative LC-MS:

6a N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-苯基乙酰胺。6a N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-phenylacetamide.

LC/MS(m/z)406.2([M+2]+)；RT＝3.58，(UV，ELSD)95.5％，100.0％。LC/MS (m/z) 406.2 ([M+2] + ); RT = 3.58, (UV, ELSD) 95.5%, 100.0%.

6b N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-3，3-二甲基丁酰胺。6b N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3,3-dimethylbutanamide.

LC/MS(m/z)384.1(M+)；RT＝3.72，(UV，ELSD)98.3％，100.0％。LC/MS (m/z) 384.1 (M + ); RT = 3.72, (UV, ELSD) 98.3%, 100.0%.

6c N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-3-苯基丙酰胺。6c N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-phenylpropanamide.

LC/MS(m/z)418.1(M+)；RT＝3.66，(UV，ELSD)98.8％，100.0％。LC/MS (m/z) 418.1 (M + ); RT = 3.66, (UV, ELSD) 98.8%, 100.0%.

6d N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-丁酰胺。6d N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-butanamide.

LC/MS(m/z)356.1(M+)；RT＝3.32，(UV，ELSD)99.4％，100.0％。LC/MS (m/z) 356.1 (M + ); RT = 3.32, (UV, ELSD) 99.4%, 100.0%.

6e戊酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基7-酰胺。6e Pentanoic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl 7-amide.

LC/MS(m/z)371.1(M+H]+)；RT＝3.55，(UV，ELSD)98.3％，100.0％。LC/MS (m/z) 371.1 (M+H] + ); RT = 3.55, (UV, ELSD) 98.3%, 100.0%.

6f环丙烷羧酸{2-氯-4-[(5-(氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺。6f Cyclopropanecarboxylic acid {2-chloro-4-[(5-(chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide.

LC/MS(m/z)355.0([M+H]+)；RT＝3.23，(UV，ELSD)98.6％，100.0％。LC/MS (m/z) 355.0 ([M+H] + ); RT = 3.23, (UV, ELSD) 98.6%, 100.0%.

6g环丁烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺。6 g cyclobutanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide.

LC/MS(m/z)368.1(M+)；RT＝3.46，(UV，ELSD)93.4％，98.5％。LC/MS (m/z) 368.1 (M + ); RT = 3.46, (UV, ELSD) 93.4%, 98.5%.

6h环戊烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺。6h Cyclopentanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide.

LC/MS(m/z)382.0(M+)；RT＝3.65，(UV，ELSD)95.2％，99.2％。LC/MS (m/z) 382.0 (M + ); RT = 3.65, (UV, ELSD) 95.2%, 99.2%.

6i环己烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-酰胺。6i Cyclohexanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide.

LC/MS(m/z)396.1(M+)；RT＝3.83，(UV，ELSD)97.3％，99.8％。LC/MS (m/z) 396.1 (M + ); RT = 3.83, (UV, ELSD) 97.3%, 99.8%.

6j N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-噻吩-2-基-乙酰胺。6j N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-thiophen-2-yl-acetamide.

LC/MS(m/z)412.0([M+2]+)；RT＝3.54，(UV，ELSD)79.3％，96.4％。LC/MS (m/z) 412.0 ([M+2] + ); RT = 3.54, (UV, ELSD) 79.3%, 96.4%.

6k N-(2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(3-甲氧基苯基)-乙酰胺。6k N-(2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(3-methoxyphenyl)-acetamide .

LC/MS(m/z)435.0([M+H]+)；RT＝3.54，(UV，ELSD)90.9％，100.0％。LC/MS (m/z) 435.0 ([M+H] + ); RT = 3.54, (UV, ELSD) 90.9%, 100.0%.

6l N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(4-氯-苯基)-乙酰胺。6l N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-chloro-phenyl)-acetamide.

LC/MS(m/z)438.0(M+)；RT＝3.78，(UV，ELSD)98.9％，100.0％。LC/MS (m/z) 438.0 (M + ); RT = 3.78, (UV, ELSD) 98.9%, 100.0%.

6m N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(4-甲氧基-苯基)-乙酰胺。6m N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-methoxy-phenyl)-ethyl amides.

LC/MS(m/z)436.0([M+2]+)；RT＝3.53，(UV，ELSD)92.0％，99.4％。LC/MS (m/z) 436.0 ([M+2] + ); RT = 3.53, (UV, ELSD) 92.0%, 99.4%.

6n N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(4-氟-苯基)-乙酰胺。6n N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-fluoro-phenyl)-acetamide.

LC/MS(m/z)421.9(M+)；RT＝3.58，(UV，ELSD)92.2％，100.0％。LC/MS (m/z) 421.9 (M + ); RT = 3.58, (UV, ELSD) 92.2%, 100.0%.

6p N-(2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2，2-二甲基丙酰胺。6p N-(2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2,2-dimethylpropanamide.

LC/MS(m/z)357.0([M+H]+)；RT＝3.34，(UV，ELSD)96.4％，99.5％。LC/MS (m/z) 357.0 ([M+H] + ); RT = 3.34, (UV, ELSD) 96.4%, 99.5%.

6q N-{2-氯-5-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-苯氧基乙酰胺。6q N-{2-Chloro-5-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-phenoxyacetamide.

LC/MS(m/z)406.9([M+H]+)；RT＝3.54，(UV，ELSD)93.9％，100.0％。LC/MS (m/z) 406.9 ([M+H] + ); RT = 3.54, (UV, ELSD) 93.9%, 100.0%.

6r N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-苯基乙酰胺。6r N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-phenylacetamide.

LC/MS(m/z)391.1([M+H]+)；RT＝3.29，(UV，ELSD)98.0％，100.0％。LC/MS (m/z) 391.1 ([M+H] + ); RT = 3.29, (UV, ELSD) 98.0%, 100.0%.

6s N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-3，3-二甲基丁酰胺。6s N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-3,3-dimethylbutanamide.

LC/MS(m/z)371.1([M+H]+)；RT＝3.40，(UV，ELSD)94.1％，98.1％。LC/MS (m/z) 371.1 ([M+H] + ); RT = 3.40, (UV, ELSD) 94.1%, 98.1%.

6t N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-丁酰胺。6t N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-butanamide.

LC/MS(m/z)343.0([M+H]+)；RT＝3.01，(UV，ELSD)77.8％，88.9％。LC/MS (m/z) 343.0 ([M+H] + ); RT = 3.01, (UV, ELSD) 77.8%, 88.9%.

6u戊酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺。6u valeric acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide.

LC/MS(m/z)357.1([M+H]+)；RT＝3.24，(UV，ELSD)95.7％，100.0％。LC/MS (m/z) 357.1 ([M+H] + ); RT = 3.24, (UV, ELSD) 95.7%, 100.0%.

6v环丙烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺。6v Cyclopropanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide.

LC/MS(m/z)340.8(M+)；RT＝2.93，(UV，ELSD)97.6％，100.0％。LC/MS (m/z) 340.8 (M + ); RT = 2.93, (UV, ELSD) 97.6%, 100.0%.

6w环丁烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基]-酰胺。6w Cyclobutanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl]-amide.

LC/MS(m/z)355.0([M+H]+)；RT＝3.15，(UV，ELSD)95.1％，100.0％。LC/MS (m/z) 355.0 ([M+H] + ); RT = 3.15, (UV, ELSD) 95.1%, 100.0%.

6x环戊烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺。6x cyclopentanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide.

LC/MS(m/z)368.8([M+H]+)；RT＝3.34，UV，ELSD)99.0％，100.0％。LC/MS (m/z) 368.8 ([M+H] + ); RT=3.34, UV, ELSD) 99.0%, 100.0%.

6y环己烷羧酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺。6y Cyclohexanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide.

LC/MS(m/z)384.0([M+2]+}；RT＝3.50，(UV，ELSD)98.2％，100.0％。LC/MS (m/z) 384.0 ([M+2] + }; RT = 3.50, (UV, ELSD) 98.2%, 100.0%.

6z N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-噻吩-2-基-乙酰胺。6z N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-thiophen-2-yl-acetamide.

LC/MS(m/z)397.0([M+H]+)；RT＝3.24(UV，ELSD)94.8％，100.0％。LC/MS (m/z) 397.0 ([M+H] + ); RT = 3.24 (UV, ELSD) 94.8%, 100.0%.

6aa N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-(3-甲氧基苯基)-乙酰胺。6aa N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(3-methoxyphenyl)-acetamide.

LC/MS(m/z)420.9([M+H]+)；RT＝3.26，(UV，ELSD)64.6％，99.8％。LC/MS (m/z) 420.9 ([M+H] + ); RT = 3.26, (UV, ELSD) 64.6%, 99.8%.

6ab N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-(4-氯苯基)-乙酰胺。6ab N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(4-chlorophenyl)-acetamide.

LC/MS(m/z)425.0([M+H]+)；RT＝3.50，(UV，ELSD)98.9％，100.0％。LC/MS (m/z) 425.0 ([M+H] + ); RT = 3.50, (UV, ELSD) 98.9%, 100.0%.

6ac N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-(4-甲氧基苯基)-乙酰胺。6ac N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(4-methoxyphenyl)-acetamide.

LC/MS(m/z)421.2([M+H]+)；RT＝3.24，(UV，ELSD)95.3％，99.6％。LC/MS (m/z) 421.2 ([M+H] + ); RT = 3.24, (UV, ELSD) 95.3%, 99.6%.

6ad N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-2-(4-氟苯基)-乙酰胺。6ad N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(4-fluorophenyl)-acetamide.

LC/MS(m/z)409.0([M+H]+)；RT＝3.31，(UV，ELSD)97.2％，100.0％。LC/MS (m/z) 409.0 ([M+H] + ); RT = 3.31, (UV, ELSD) 97.2%, 100.0%.

6ae 2，3-二氢-苯并[1，4]二噁烯-6-甲酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基J-苯基)-酰胺。6ae 2,3-dihydro-benzo[1,4]dioxene-6-carboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino (J-phenyl) - amides.

LC/MS(m/z)434.9([M+H]+)；RT＝3.21，(UV，ELSD)92.7％，100.0％。LC/MS (m/z) 434.9 ([M+H] + ); RT = 3.21, (UV, ELSD) 92.7%, 100.0%.

6af 2，3-二氢-苯并呋喃-5-甲酸{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-酰胺。6af 2,3-Dihydro-benzofuran-5-carboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide.

LC/MS(m/z)419.3([M+H]+)；RT＝3.26，(UV，ELSD)81.6％，94.8％。LC/MS (m/z) 419.3 ([M+H] + ); RT = 3.26, (UV, ELSD) 81.6%, 94.8%.

6ag N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-氨基]-苯基}-3-环己基丙酰胺。6ag N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-3-cyclohexylpropionamide.

LC/MS(m/z)411.1([M+H]+)；RT＝3.89，(UV，ELSD)95.3％，99.5％。LC/MS (m/z) 411.1 ([M+H] + ); RT = 3.89, (UV, ELSD) 95.3%, 99.5%.

6ah N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-2，2二甲基丙酰胺。6ah N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-2,2-dimethylpropanamide.

LC/MS(m/z)350.1(M+)；RT＝2.98，(UV，ELSD)91.8％，99.1％。LC/MS (m/z) 350.1 (M + ); RT = 2.98, (UV, ELSD) 91.8%, 99.1%.

6ai N-{4-[(5-氯-噻吩-2-基甲基)-(甲基氨基]-2-甲基-苯基}-2-苯基乙酰胺。6ai N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methylamino]-2-methyl-phenyl}-2-phenylacetamide.

LC/MS(m/z)384.1(M；RT＝3.04，(UV，ELSD)95.8％，100.0％。LC/MS (m/z) 384.1 (M; RT = 3.04, (UV, ELSD) 95.8%, 100.0%.

6aj N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-3，3-二甲基丁酰胺。6aj N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-3,3-dimethylbutanamide.

LC/MS(m/z)364.1(M+)；RT＝3.10，(UV，ELSD)93.0％，99.7％。LC/MS (m/z) 364.1 (M + ); RT = 3.10, (UV, ELSD) 93.0%, 99.7%.

6ak N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-3-苯基丙酰胺。6ak N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-3-phenylpropanamide.

LC/MS(rn/z)399.1([M+H]+)；RT＝3.12，(UV，ELSD)98.2％，99.9％。LC/MS (rn/z) 399.1 ([M+H] + ); RT = 3.12, (UV, ELSD) 98.2%, 99.9%.

6al N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-丁酰胺。6al N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-butanamide.

LC/MS(m/z)337.3([M+H]+)；RT＝2.68，(UV，ELSD)92.5％，99.7％。LC/MS (m/z) 337.3 ([M+H] + ); RT = 2.68, (UV, ELSD) 92.5%, 99.7%.

6am 2，2，2-三氯-N-(4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基}-乙酰胺。6am 2,2,2-Trichloro-N-(4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-acetamide.

LC/MS(m/z)411.9([M+H]+)；RT＝3.65，(UV，ELSD)97.3％，100.0％。LC/MS (m/z) 411.9 ([M+H] + ); RT = 3.65, (UV, ELSD) 97.3%, 100.0%.

6an环丙烷羧酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基-苯基)-酰胺。6an Cyclopropanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl)-amide.

LC/MS(m/z)335.1([M+H]+)；RT＝2.58，(UV，ELSD)86.4％，97.8％。LC/MS (m/z) 335.1 ([M+H] + ); RT = 2.58, (UV, ELSD) 86.4%, 97.8%.

6ao环丁烷羧酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-酰胺。6ao Cyclobutanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-amide.

LC/MS(m/z)348.0(M+)；RT＝2.79，(UV，ELSD)95.4％，100.0％。LC/MS (m/z) 348.0 (M + ); RT = 2.79, (UV, ELSD) 95.4%, 100.0%.

6ap环戊烷羧酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-酰胺。6ap Cyclopentanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-amide.

LC/MS(m/z)363.2([M+H]+)；RT＝2.99，(UV，ELSD)97.7％，99.9％。LC/MS (m/z) 363.2 ([M+H] + ); RT = 2.99, (UV, ELSD) 97.7%, 99.9%.

6aq环己烷羧酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-酰胺。6aq Cyclohexanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-amide.

LC/MS(m/z)377.1([M+H]+)；RT＝3.16，(UV，ELSD)88.0％，97.5％。LC/MS (m/z) 377.1 ([M+H] + ); RT = 3.16, (UV, ELSD) 88.0%, 97.5%.

6ar N-(4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-2-噻吩-2-基-乙酰胺。6ar N-(4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-thiophen-2-yl-acetamide.

LC/MS(m/z)390.0(M+)；RT＝3.02，(UV，ELSD)97.2％，99.9％。LC/MS (m/z) 390.0 (M + ); RT = 3.02, (UV, ELSD) 97.2%, 99.9%.

6as N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-2-(3-甲氧基苯基)-乙酰胺。6as N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-(3-methoxyphenyl)-acetamide .

LC/MS(m/z)416.0([M+2]+)；RT＝3.03，(UV，ELSD)92.9％，100.0％。LC/MS (m/z) 416.0 ([M+2] + ); RT = 3.03, (UV, ELSD) 92.9%, 100.0%.

6at N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-丙酰胺酸甲酯。6at N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-propionamic acid methyl ester.

LC/MS(m/z)366.1(M+)；RT＝2.53，(UV，ELSD)94.5％，100.0％。LC/MS (m/z) 366.1 (M + ); RT = 2.53, (UV, ELSD) 94.5%, 100.0%.

6au 2-(4-氯苯基)-N-{4-[(5-氯-噻吩-2-基甲基-(甲基)氨基]-2-甲基苯基}-乙酰胺。6au 2-(4-Chlorophenyl)-N-{4-[(5-chloro-thiophen-2-ylmethyl-(methyl)amino]-2-methylphenyl}-acetamide.

LC/MS(m/z)418.1(M+)；RT＝3.31，(UV，ELSD)97.3％，99.9％。LC/MS (m/z) 418.1 (M + ); RT = 3.31, (UV, ELSD) 97.3%, 99.9%.

6av N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-2-(4-甲氧基苯基)-乙酰胺。6av N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-(4-methoxyphenyl)-acetamide .

LC/MS(m/z)415.2([M+H]+)；RT＝2.99，(UV，ELSD)87.8％，98.1％。LC/MS (m/z) 415.2 ([M+H] + ); RT = 2.99, (UV, ELSD) 87.8%, 98.1%.

6aw N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-2-(4-氟苯基)-乙酰胺。6aw N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-(4-fluorophenyl)-acetamide.

LC/MS(m/z)403.2([M+H]+)；RT＝3.10，(UV，ELSD)94.5％，99.9％。LC/MS (m/z) 403.2 ([M+H] + ); RT = 3.10, (UV, ELSD) 94.5%, 99.9%.

6ax N-{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-3-环己基丙酰胺。6ax N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-3-cyclohexylpropionamide.

LC/MS(m/z)405.1([M+H]+)；RT＝3.61，(UV，ELSD)92.6％，98.9％。LC/MS (m/z) 405.1 ([M+H] + ); RT = 3.61, (UV, ELSD) 92.6%, 98.9%.

6ba{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸苯酯。6ba{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid phenyl ester.

LC/MS(m/z)406.2(M+)；RT＝3.78，(UV，ELSD)96.3％，99.4％。LC/MS (m/z) 406.2 (M + ); RT = 3.78, (UV, ELSD) 96.3%, 99.4%.

6bb{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸苄酯。6bb {2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid benzyl ester.

LC/MS(m/z)422.1([M+2]+)；RT＝3.91，(UV，ELSD)92.7％，99.3％。LC/MS (m/z) 422.1 ([M+2] + ); RT = 3.91, (UV, ELSD) 92.7%, 99.3%.

6bc{2-氯-4[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸异丁酯。6bc {2-Chloro-4[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid isobutyl ester.

LC/MS(m/z)388.1([M+2]+)；RT＝3.99，(UV，ELSD)99.0％，100.0％。LC/MS (m/z) 388.1 ([M+2] + ); RT = 3.99, (UV, ELSD) 99.0%, 100.0%.

6bd{2-氯-4[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丁酯。6bd{Butyl 2-chloro-4[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamate.

LC/MS(m/z)386.0(M+)；RT＝4.03，(UV，ELSD)97.1％，99.9％。LC/MS (m/z) 386.0 (M + ); RT = 4.03, (UV, ELSD) 97.1%, 99.9%.

6be{2-氯-4[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸己酯。6be {2-Chloro-4[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-hexylcarbamate.

LC/MS(m/z)415.9([M+2]+)；RT＝4.44，(UV，ELSD)91.7％，98.9％。LC/MS (m/z) 415.9 ([M+2] + ); RT = 4.44, (UV, ELSD) 91.7%, 98.9%.

6bf 2-氯-4-(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基)-氨基甲酸4-硝基苄酯。6bf 4-nitrobenzyl 2-chloro-4-(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl)-carbamate.

LC/MS(m/z)465.0(M+)；RT＝3.80，(UV，ELSD)91.7％，97.9％。LC/MS (m/z) 465.0 (M + ); RT = 3.80, (UV, ELSD) 91.7%, 97.9%.

6bg{2-氯-4[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丁-3-烯酯。6bg {2-Chloro-4[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamate but-3-enyl ester.

LC/MS(m/z)383.9(M+)；RT＝3.82，(UV，ELSD)93.9％，99.6％。LC/MS (m/z) 383.9 (M + ); RT = 3.82, (UV, ELSD) 93.9%, 99.6%.

6bh{2-氯-4[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸丁-2-炔酯。6bh {2-Chloro-4[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid but-2-ynyl ester.

LC/MS(m/z)384.0([M+2]+)；RT＝3.61，(UV，ELSD)76.3％，99.0％。LC/MS (m/z) 384.0 ([M+2] + ); RT = 3.61, (UV, ELSD) 76.3%, 99.0%.

6bi{2-氯-4[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸2，2-二甲基丙酯。6bi{2-Chloro-4[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 2,2-dimethylpropyl ester.

LC/MS(m/z)399.9(M+)；RT＝4.11，(UV，ELSD)98.8％，99.6％。LC/MS (m/z) 399.9 (M + ); RT = 4.11, (UV, ELSD) 98.8%, 99.6%.

6bj{2-氯-4[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸2-氯苄酯。6bj {2-Chloro-4[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 2-chlorobenzyl ester.

LC/MS(m/z)453.9(M+)；RT＝4.12，(UV，ELSD)97.5％，99.8％。LC/MS (m/z) 453.9 (M + ); RT = 4.12, (UV, ELSD) 97.5%, 99.8%.

6bk{2-氯-4[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸3-氯丙酯。6bk {2-Chloro-4[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 3-chloropropyl ester.

LC/MS(m/z)407.9([M+2]+)；RT＝3.72，(UV，ELSD)88.7％，97.5％。LC/MS (m/z) 407.9 ([M+2] + ); RT = 3.72, (UV, ELSD) 88.7%, 97.5%.

6bl{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-氨基甲酸2-苄氧基乙酯。6bl {2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 2-benzyloxyethyl ester.

LC/MS(m/z)464.0(M+)；RT＝3.86，(UV，ELSD)89.1％，98.7％。LC/MS (m/z) 464.0 (M + ); RT = 3.86, (UV, ELSD) 89.1%, 98.7%.

6bm 3-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-1-甲基-1-丙基-脲。6bm 3-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-1-methyl-1-propyl-urea.

LC/MS(m/z)388.1([M+3]+)；RT＝3.38，(UV，ELSD)86.0％，99.5％。LC/MS (m/z) 388.1 ([M+3] + ); RT = 3.38, (UV, ELSD) 86.0%, 99.5%.

6bo 1-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-3-(2-氟苯基)-脲。6bo 1-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-(2-fluorophenyl)-urea.

LC/MS(m/z)425.0([M+2]+)；RT＝3.65，(UV，ELSD)94.9％，99.9％。LC/MS (m/z) 425.0 ([M+2] + ); RT = 3.65, (UV, ELSD) 94.9%, 99.9%.

实施例7Example 7

7a N-(4-{[5-(4-氯苯氧基)-1，3-二甲基-1H-吡唑-4-基甲基]-氨基}-2-甲基苯基)-2，2-二甲基丙酰胺。7a N-(4-{[5-(4-chlorophenoxy)-1,3-dimethyl-1H-pyrazol-4-ylmethyl]-amino}-2-methylphenyl)- 2,2-Dimethylpropanamide.

将N-(4-氨基-2-甲基苯基)-2，2-二甲基丙酰胺(300mg，1.45mmol)和5-(4-氯苯氧基)-1，3-二甲基-1H-吡唑-4-甲醛(360mg，1.45mmol)在乙腈(4mL)中的混合物在微波辐射下在170℃下加热和搅拌20分钟。将所得的反应混合物小心加入到氰基硼氢化钠(0.36g)在甲醇中的溶液中，然后向其中加入醋酸(1mL)。在60分钟后，将其在乙酸乙酯和饱和碳酸氢钠水溶液之间进行分配并对有机层进行蒸发。用SiO2闪柱色谱对标题化合物进行分离，用庚烷-乙酸乙酯进行洗脱，然后用庚烷使之从乙酸乙酯中沉淀。收率为112mg，18％。LC/MS-TOF(m/z)441；RT＝2.34，(UV，ELSD)98％，100％。1H NMR(DMSO-d6)：1.18(s，9H)，1.96(s，3H)，2.15(s，3H)，3.47(s，3H)，3.75(d，2H)，5.4(t，1H，NH)，6.29(dd，1H)，6.33(d，1H)，6.24(d，1H)，6.99(d，2H)，7.41(d，2H)，8.58(s，1H，NH)。N-(4-amino-2-methylphenyl)-2,2-dimethylpropanamide (300mg, 1.45mmol) and 5-(4-chlorophenoxy)-1,3-dimethyl - A mixture of 1H-pyrazole-4-carbaldehyde (360 mg, 1.45 mmol) in acetonitrile (4 mL) was heated and stirred at 170° C. for 20 minutes under microwave irradiation. The resulting reaction mixture was carefully added to a solution of sodium cyanoborohydride (0.36 g) in methanol, to which was then added acetic acid (1 mL). After 60 minutes, it was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate and the organic layer was evaporated. The title compound was isolated by flash chromatography on SiO2 , eluting with heptane-ethyl acetate, and then precipitated from ethyl acetate with heptane. Yield 112mg, 18%. LC/MS-TOF (m/z) 441; RT = 2.34, (UV, ELSD) 98%, 100%. 1 H NMR (DMSO-d 6 ): 1.18(s, 9H), 1.96(s, 3H), 2.15(s, 3H), 3.47(s, 3H), 3.75(d, 2H), 5.4(t, 1H , NH), 6.29 (dd, 1H), 6.33 (d, 1H), 6.24 (d, 1H), 6.99 (d, 2H), 7.41 (d, 2H), 8.58 (s, 1H, NH).

由相应的苯胺和醛相似地制备下面的化合物：The following compounds were prepared analogously from the corresponding anilines and aldehydes:

7b 2，2-二甲基-N-{2-甲基-4-[(6-苯氧基吡啶-3-基甲基)-氨基]-苯基}-丙酰胺。7b 2,2-Dimethyl-N-{2-methyl-4-[(6-phenoxypyridin-3-ylmethyl)-amino]-phenyl}-propionamide.

LC/MS-TOF(m/z)390；RT＝2.54，(L1V，ELSD)90％，100％。LC/MS-TOF (m/z) 390; RT = 2.54, (L1V, ELSD) 90%, 100%.

7c 2，2-二甲基-N-{2-甲基-4-[(3-甲基-5-苯基异噁唑-4-基甲基)-氨基]-苯基}-丙酰胺。7c 2,2-Dimethyl-N-{2-methyl-4-[(3-methyl-5-phenylisoxazol-4-ylmethyl)-amino]-phenyl}-propionamide .

LC/MS-TOF(m/z)378；RT＝2.82，(UV，ELSD)97％，100％。1HNMR(DMSO-d6)：1.19(s，9H)，1.96(s，3H)，2.3(s，3H)，4.11(d，2H)，5.85(t，1H，NH)，6.42(overlappingm，2H)，6.79(d，1H)，7.55(m，3H)，7.72(d，2H)，8.61(s，1H，NH)。LC/MS-TOF (m/z) 378; RT = 2.82, (UV, ELSD) 97%, 100%. 1 HNMR (DMSO-d 6 ): 1.19 (s, 9H), 1.96 (s, 3H), 2.3 (s, 3H), 4.11 (d, 2H), 5.85 (t, 1H, NH), 6.42 (overlappingm, 2H), 6.79 (d, 1H), 7.55 (m, 3H), 7.72 (d, 2H), 8.61 (s, 1H, NH).

7d 2-(4-氟苯基)-N-{2-甲基-4-[(6-三氟甲基吡啶-3-基甲基)-氨基]-苯基}-乙酰胺。7d 2-(4-Fluorophenyl)-N-{2-methyl-4-[(6-trifluoromethylpyridin-3-ylmethyl)-amino]-phenyl}-acetamide.

LC/MS-TOF(m/z)418.4([M+H]+)；RT＝2.75，(UV，ELSD)99％，100％。1H NMR(DMSO-d6)：1.98(s，3H)，3.54(s，2H)，4.39(d，2H)，6.28(t，1H，NH)，6.36(dd，1H)，6.43(d，1H)，6.91(d，1H)，7.14(t，2H)，7.35(dd，2H)，7.85(d，1H)，7.99(dd，1H)，8.74(d，1H)，9.21(s，1H，NH)。LC/MS-TOF (m/z) 418.4 ([M+H] + ); RT = 2.75, (UV, ELSD) 99%, 100%. 1 H NMR (DMSO-d 6 ): 1.98(s, 3H), 3.54(s, 2H), 4.39(d, 2H), 6.28(t, 1H, NH), 6.36(dd, 1H), 6.43(d , 1H), 6.91(d, 1H), 7.14(t, 2H), 7.35(dd, 2H), 7.85(d, 1H), 7.99(dd, 1H), 8.74(d, 1H), 9.21(s, 1H, NH).

7e 3，3-二甲基-N-{2-甲基-4-[(6-三氟甲基吡啶-3-基甲基)-氨基]-苯基}-丁酰胺。7e 3,3-Dimethyl-N-{2-methyl-4-[(6-trifluoromethylpyridin-3-ylmethyl)-amino]-phenyl}-butanamide.

LC/MS-TOF(m/z)380.5([M+H]+)；RT＝2.75，(UV，ELSD)97％，99％。LC/MS-TOF (m/z) 380.5 ([M+H] + ); RT = 2.75, (UV, ELSD) 97%, 99%.

7f 2-(4-氟苯基)-N-{2-甲基-4-[(6-p-甲苯氧基吡啶-3-基甲基)-氨基]-苯基)-乙酰胺。7f 2-(4-Fluorophenyl)-N-{2-methyl-4-[(6-p-tolyloxypyridin-3-ylmethyl)-amino]-phenyl)-acetamide.

LC/MS(m/z)456.2([M+H]+)；RT＝2.79，(UV，ELSD)82.5％，99.8％。LC/MS (m/z) 456.2 ([M+H] + ); RT = 2.79, (UV, ELSD) 82.5%, 99.8%.

7g 3，3-二甲基-N-{2-甲基-4-[(6-p-甲苯氧基吡啶-3-基甲基)-氨基]-苯基}-丁酰胺。7 g 3,3-Dimethyl-N-{2-methyl-4-[(6-p-tolyloxypyridin-3-ylmethyl)-amino]-phenyl}-butanamide.

LC/MS(m/z)418.3([M+H]+)；RT＝2.75，(UV，ELSD)62％，93％。LC/MS (m/z) 418.3 ([M+H] + ); RT = 2.75, (UV, ELSD) 62%, 93%.

7h N-(4-{[6-(4-氰基苯氧基)-吡啶-3-基甲基]-氨基}-2-甲基苯基)-2-(4-氟苯基)-乙酰胺。7h N-(4-{[6-(4-cyanophenoxy)-pyridin-3-ylmethyl]-amino}-2-methylphenyl)-2-(4-fluorophenyl)- acetamide.

LC/MS(m/z)467.2([M+H]+)；RT＝2.65，(UV，ELSD)72％，96％。LC/MS (m/z) 467.2 ([M+H] + ); RT = 2.65, (UV, ELSD) 72%, 96%.

7i N-{4-[(6-氯吡啶-3-基甲基)-氨基]-2-甲基苯基}-2-(4-氟苯基)-乙酰胺.7i N-{4-[(6-chloropyridin-3-ylmethyl)-amino]-2-methylphenyl}-2-(4-fluorophenyl)-acetamide.

LC/MS(m/z)384.1([M+H)+)；RT＝2.46，(UV，ELSD)87％，99％。LC/MS (m/z) 384.1 ([M+H)+); RT = 2.46, (UV, ELSD) 87%, 99%.

7j 2-(4-氟苯基)-N-{2-甲基-4-[(4-甲基-2-苯基嘧啶-5-基甲基)-氨基]-苯基}-乙酰胺。7j 2-(4-fluorophenyl)-N-{2-methyl-4-[(4-methyl-2-phenylpyrimidin-5-ylmethyl)-amino]-phenyl}-acetamide .

LC/MS(m/z)441.4([M+H]+)；RT＝2.97，(UV，ELSD)90％，100％。LC/MS (m/z) 441.4 ([M+H] + ); RT = 2.97, (UV, ELSD) 90%, 100%.

7k 3，3-二甲基-N-{2-甲基-4-[(2-苯基嘧啶-5-基甲基)-氨基]-苯基}-丁酰胺。7k 3,3-Dimethyl-N-{2-methyl-4-[(2-phenylpyrimidin-5-ylmethyl)-amino]-phenyl}-butanamide.

LC/MS-TOF(m/z)389.6([M+H]+)；RT＝2.83，(UV，ELSD)89％，95％。LC/MS-TOF (m/z) 389.6 ([M+H] + ); RT = 2.83, (UV, ELSD) 89%, 95%.

实施例8Example 8

8a{4-[(5-二甲基氨基-3-甲基-苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯8a{4-[(5-Dimethylamino-3-methyl-benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester

将(4-氨基-2-甲基苯基)-氨基甲酸丙酯(21mg，0.10mmol)和5-二甲基氨基-3-甲基-苯并[b]噻吩-2-甲醛(26mg，0.12mmol)在乙腈(0.5mL)中的溶液用Personal Chemistry Smith Syntesizer微波装置在170℃下加热2分钟。在冷却至室温后，向其中加入氰基硼氢化钠(25mg，0.40mmol)在甲醇(0.1mL)中的溶液，然后加入醋酸(50μL)并将该混合物搅拌30分钟。将其在饱和碳酸氢钠水溶液(10mL)和乙酸乙酯(10mL)之间进行分配并将有机层用硫酸钠进行干燥并对其进行蒸发。制备LC-MS提供了标题化合物(32mg，收率为77％)。(4-Amino-2-methylphenyl)-propyl carbamate (21 mg, 0.10 mmol) and 5-dimethylamino-3-methyl-benzo[b]thiophene-2-carbaldehyde (26 mg, A solution of 0.12 mmol) in acetonitrile (0.5 mL) was heated at 170° C. for 2 minutes using a Personal Chemistry Smith Syntesizer microwave unit. After cooling to room temperature, a solution of sodium cyanoborohydride (25 mg, 0.40 mmol) in methanol (0.1 mL) was added thereto, followed by acetic acid (50 μL) and the mixture was stirred for 30 minutes. It was partitioned between saturated aqueous sodium bicarbonate (10 mL) and ethyl acetate (10 mL) and the organic layer was dried over sodium sulfate and evaporated. Preparative LC-MS provided the title compound (32 mg, 77% yield).

LC/MS-TOF(m/z)412.4([M+H]+)；RT＝2.02，(UV，ELSD)81％，97％。LC/MS-TOF (m/z) 412.4 ([M+H] + ); RT = 2.02, (UV, ELSD) 81%, 97%.

由适宜的苯胺和醛相似地制备下面的化合物：The following compounds are similarly prepared from the appropriate aniline and aldehyde:

8b[4-(3-氟-4-三氟甲基-苄基氨基)-2-甲基苯基]-氨基甲酸乙酯8b[4-(3-fluoro-4-trifluoromethyl-benzylamino)-2-methylphenyl]-ethyl carbamate

LC/MS(m/z)371.2([M+H]+)；RT＝3.10，(UV，ELSD)83％，96％。LC/MS (m/z) 371.2 ([M+H] + ); RT = 3.10, (UV, ELSD) 83%, 96%.

8c[4-(4-氯-苄基氨基)-2-甲基苯基]-氨基甲酸乙酯8c[4-(4-Chloro-benzylamino)-2-methylphenyl]-carbamate ethyl ester

LC/MS(m/z)319.0([M+H]+)；RT＝2.57，(UV，ELSD)79％，95％。LC/MS (m/z) 319.0 ([M+H] + ); RT = 2.57, (UV, ELSD) 79%, 95%.

8d{4-[(6＝甲氧基-苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯8d{4-[(6=methoxy-benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamate propyl ester

LC/MS-TOF(m/z)384.4(M+)；RT＝3.07，(UV，ELSD)97％，94％。LC/MS-TOF (m/z) 384.4 (M + ); RT = 3.07, (UV, ELSD) 97%, 94%.

8e{4-[(7-二甲基氨基-苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸丙酯8e{4-[(7-Dimethylamino-benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester

LC/MS-TOF(m/z)398.4([M+H]+)；RT＝2.64，(UV，ELSD)97％，100％。LC/MS-TOF (m/z) 398.4 ([M+H] + ); RT = 2.64, (UV, ELSD) 97%, 100%.

8f{4-[(6-甲氧基-苯并[b]噻吩-2-基甲基)-氨基]-2-甲基苯基}-氨基甲酸乙酯8f {4-[(6-methoxy-benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-urethane

LC/MS-TOF(m/z)370.4(M+)；RT＝2.79，(LW，ELSD)98％，99％。LC/MS-TOF (m/z) 370.4 (M + ); RT = 2.79, (LW, ELSD) 98%, 99%.

8g 4-[(3-甲基-4-丙氧基羰基氨基-苯基氨基)-甲基]-苯甲酸甲酯8g 4-[(3-Methyl-4-propoxycarbonylamino-phenylamino)-methyl]-benzoic acid methyl ester

LC/MS(m/z)356.1(NI)；RT＝2.52，(UV，ELSD)80％，100％。LC/MS (m/z) 356.1 (NI); RT = 2.52, (UV, ELSD) 80%, 100%.

实施例9Example 9

9a N-[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-丁酰胺9a N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-butanamide

在0℃下，向(4-氨基-3-甲基苯基)-(4-三氟甲基-苄基)-氨基甲酸叔-丁酯(500mg，1.31mmol)在无水四氢呋喃(10mL)中的溶液中加入吡啶(159μL，1.97mmol)，然后向其中滴加丁酰氯(164μL，1.58mmol)。在5分钟后，使该反应混合物加温至室温并将其继续搅拌1小时。然后，将该反应混合物用乙酸乙酯稀释，用2N HCl、和碳酸氢钠水溶液(两次)、和盐水进行洗涤，然后用硫酸镁干燥。将溶剂真空蒸发并将残余物溶解于1∶1的二氯甲烷和三氟醋酸混合物中。在30分钟后，将该混合物在室温下蒸发至干燥，将残余物溶解于乙酸乙酯(10mL)中，将该溶液用饱和碳酸氢钠水溶液洗涤两次，用水洗涤两次，然后用硫酸钠进行干燥。蒸发掉溶剂并将残余物用乙酸乙酯∶庚烷进行重结晶，得到无色固体形式的标题化合物(226mg，49％)。To (4-amino-3-methylphenyl)-(4-trifluoromethyl-benzyl)-carbamic acid tert-butyl ester (500 mg, 1.31 mmol) in anhydrous tetrahydrofuran (10 mL) at 0 °C Pyridine (159 μL, 1.97 mmol) was added to the solution in , and then butyryl chloride (164 μL, 1.58 mmol) was added dropwise thereto. After 5 minutes, the reaction mixture was allowed to warm to room temperature and stirring was continued for 1 hour. The reaction mixture was then diluted with ethyl acetate, washed with 2N HCl, and aqueous sodium bicarbonate (twice), and brine, then dried over magnesium sulfate. The solvent was evaporated in vacuo and the residue was dissolved in a 1:1 mixture of dichloromethane and trifluoroacetic acid. After 30 minutes, the mixture was evaporated to dryness at room temperature, the residue was dissolved in ethyl acetate (10 mL), the solution was washed twice with saturated aqueous sodium bicarbonate solution, twice with water, then with sodium sulfate to dry. The solvent was evaporated and the residue was recrystallized from ethyl acetate:heptane to give the title compound (226 mg, 49%) as a colorless solid.

1H NMR(DMSO-d6)：0.90(t，3H)，1.58(sextet，2H)，2.01(s，3H)，2.19(t，2H)，4.35(d，2H)，6.24(t，1H)，6.32(dd，1H)，6.41(d，1H)，6.87(d，1H)，7.55(d，2H)，7.67(d，2H)，8.91(s，1H).LC/MS(m/z)350.2(M+)；RT＝2.77，(UV，ELSD)95％，100％。 1 H NMR (DMSO-d 6 ): 0.90(t, 3H), 1.58(sextet, 2H), 2.01(s, 3H), 2.19(t, 2H), 4.35(d, 2H), 6.24(t, 1H ), 6.32(dd, 1H), 6.41(d, 1H), 6.87(d, 1H), 7.55(d, 2H), 7.67(d, 2H), 8.91(s, 1H).LC/MS(m/ z) 350.2 (M + ); RT = 2.77, (UV, ELSD) 95%, 100%.

类似地制备下面的化合物：The following compounds were prepared analogously:

9b[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-氨基甲酸乙酯9b[2-Methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-urethane

收率：254mg(55％)。Yield: 254 mg (55%).

LC/MS(m/z)353.2([M+H]+)；RT＝2.93，(W1，ELSD)97％，100％。LC/MS (m/z) 353.2 ([M+H] + ); RT = 2.93, (W1, ELSD) 97%, 100%.

1H NMR(DMSO-d6)：1.19(br.s，3H)，2.03(s，3H)，4.02(q，2H)，4.35(s，2H)，6.29(br.s，1H)，6.33(dd，1H)，6.41(d，1H)，6.86(br.d，1H)，7.55(d，2H)，7.67(d，2H)，8.39(br.s，1H)。 1 H NMR (DMSO-d 6 ): 1.19 (br.s, 3H), 2.03 (s, 3H), 4.02 (q, 2H), 4.35 (s, 2H), 6.29 (br.s, 1H), 6.33 (dd, 1H), 6.41 (d, 1H), 6.86 (br.d, 1H), 7.55 (d, 2H), 7.67 (d, 2H), 8.39 (br.s, 1H).

实施例10Example 10

10a N-[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-2-哌啶-1-基-乙酰胺10a N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-piperidin-1-yl-acetamide

向(4-氨基-3-甲基苯基)-(4-三氟甲基-苄基)-氨基甲酸叔-丁酯(15.2mg，40μmol)在DMF(100μL)中的溶液中加入O-(7-氮杂苯并三唑-1-基)-N，N，N′，N′-四甲基脲鎓六氟磷酸盐(HATU，27.4mg，72μmol)在DMF(100μL)中的溶液，然后向其中加入i-PR2NEt(25μL，144μmol)和哌啶-1-基-醋酸(8.6mg，60μmol)。将所得的混合物在室温下振荡3小时，其后，将其用乙酸乙酯(10mL)稀释，用饱和氯化铵水溶液进行洗涤(2×10mL)，用硫酸钠进行干燥，并将其进行蒸发。将残余物在FlashMaster系统上进行纯化(二氧化硅，用庚烷/乙酸乙酯混合物进行洗脱)，得到白色固体形式的[3-甲基-4-(2-哌啶-1-基-乙酰基氨基)-苯基]-(4-三氟甲基苄基)-氨基甲酸叔-丁酯(10.7mg，53％)。将其溶解于二氯甲烷(200μL)和三氟醋酸(200μL)中，并将该溶液在室温下放置30分钟，其后，蒸发掉挥发性物质并将残余物在0.1mmHg和+40℃下真空干燥1小时。以定量的收率得到黄色半固体形式的标题化合物的三氟醋酸加成盐。To a solution of (4-amino-3-methylphenyl)-(4-trifluoromethyl-benzyl)-carbamic acid tert-butyl ester (15.2 mg, 40 μmol) in DMF (100 μL) was added O- Solution of (7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU, 27.4 mg, 72 μmol) in DMF (100 μL) , and then i-PR 2 NEt (25 μL, 144 μmol) and piperidin-1-yl-acetic acid (8.6 mg, 60 μmol) were added thereto. The resulting mixture was shaken at room temperature for 3 hours, after which it was diluted with ethyl acetate (10 mL), washed with saturated aqueous ammonium chloride (2 x 10 mL), dried over sodium sulfate, and evaporated . The residue was purified on a FlashMaster system (silica, eluting with a heptane/ethyl acetate mixture) to give [3-methyl-4-(2-piperidin-1-yl- Acetylamino)-phenyl]-(4-trifluoromethylbenzyl)-carbamic acid tert-butyl ester (10.7 mg, 53%). It was dissolved in dichloromethane (200 μL) and trifluoroacetic acid (200 μL), and the solution was left at room temperature for 30 minutes, after which, the volatile substances were evaporated and the residue was heated at 0.1 mmHg and +40° C. Vacuum dry for 1 hour. The trifluoroacetic acid addition salt of the title compound was obtained in quantitative yield as a yellow semisolid.

LC/MS-TOF(m/z)406.4([M+H]+)；RT＝2.02，(UV，ELSD)99％，98％。LC/MS-TOF (m/z) 406.4 ([M+H] + ); RT = 2.02, (UV, ELSD) 99%, 98%.

由苯胺和羧酸相似地制备下面的化合物：The following compounds are similarly prepared from aniline and carboxylic acid:

10b N-[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-2-吡咯烷-1-基-乙酰胺10b N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-pyrrolidin-1-yl-acetamide

LC/MS-TOF(m/z)392.3([M+H]+)，RT＝2.04，(UV，ELSD)98％，99％。LC/MS-TOF (m/z) 392.3 ([M+H] + ), RT=2.04, (UV, ELSD) 98%, 99%.

10c N-[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-2-吗啉-4-基-乙酰胺10c N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-morpholin-4-yl-acetamide

LC/MS-TOF(m/z)408.3([M+H]+)；RT＝1.98，(UV，ELSD)99％，100％。LC/MS-TOF (m/z) 408.3 ([M+H] + ); RT = 1.98, (UV, ELSD) 99%, 100%.

10d(S)-2-氨基-4-甲基-戊酸[2-甲基-4-(4-三氟甲基苄基氨基)-苯基]-酰胺10d(S)-2-Amino-4-methyl-pentanoic acid [2-methyl-4-(4-trifluoromethylbenzylamino)-phenyl]-amide

LC/MS-TOF(m/z)394([M+H]+)；RT＝2.12，(UV，ELSD)75％，73％。LC/MS-TOF (m/z) 394 ([M+H] + ); RT = 2.12, (UV, ELSD) 75%, 73%.

10e(R)-2-氨基-4-甲基-戊酸[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-酰胺10e(R)-2-Amino-4-methyl-pentanoic acid [2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-amide

LC/MS-TOF(m/z)394([M+H]+)；RT＝2.29，(UV，ELSD)89％，100％。LC/MS-TOF (m/z) 394 ([M+H] + ); RT = 2.29, (UV, ELSD) 89%, 100%.

10f 1-氨基-环丙烷羧酸[2-甲基-4-(4-三氟甲基-苄基氨基)-苯基]-酰胺10f 1-Amino-cyclopropanecarboxylic acid [2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-amide

LC/MS-TOF(m/z)365；RT＝1.98，(UV，ELSD)94％，89％。LC/MS-TOF (m/z) 365; RT = 1.98, (UV, ELSD) 94%, 89%.

实施例11 戊酸{4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-2-甲基苯基}-酰胺Example 11 Valeric acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-amide

向N(4)-(5-氯-噻吩-2-基甲基)-2，N(4)-二甲基-苯-1，4-二胺(54mg，0.20mmol)和三乙胺(84L，0.60mmol)在无水四氢呋喃(1mL)中的溶液中加入戊酰氯(36，L，0.30mmol)并将该混合物在室温下搅拌1小时，其后，将其在饱和碳酸氢钠水溶液(5mL)和乙酸乙酯(5mL)之间进行分配。将有机层用硫酸钠进行干燥，蒸发掉挥发性物质，将残余物在FlashMaster系统上进行纯化(二氧化硅，用庚烷/乙酸乙酯混合物进行洗脱)，得到白色固体形式的标题化合物(61mg，86％)。To N(4)-(5-chloro-thiophen-2-ylmethyl)-2,N(4)-dimethyl-benzene-1,4-diamine (54 mg, 0.20 mmol) and triethylamine ( 84 L, 0.60 mmol) in anhydrous tetrahydrofuran (1 mL) was added valeryl chloride (36, L, 0.30 mmol) and the mixture was stirred at room temperature for 1 hour, after which it was dissolved in saturated aqueous sodium bicarbonate ( 5 mL) and ethyl acetate (5 mL). The organic layer was dried over sodium sulfate, the volatiles were evaporated and the residue was purified on a FlashMaster system (silica, eluting with a heptane/ethyl acetate mixture) to give the title compound as a white solid ( 61 mg, 86%).

LC/MS(m/z)351.3([M+H]+)；RT＝3.06，(UV，ELSD)100％，99％。LC/MS (m/z) 351.3 ([M+H] + ); RT = 3.06, (UV, ELSD) 100%, 99%.

实施例12Example 12

12a {2-苄氧基-4-[(4-氟苄基)-(甲基)氨基]-苯基}-硫代氨基甲酸S-乙酯12a {2-Benzyloxy-4-[(4-fluorobenzyl)-(methyl)amino]-phenyl}-thiocarbamic acid S-ethyl ester

将(3-苄氧基-4-硝基苯基)(4-氟苄基)甲基胺(50mg)溶解于四氢呋喃(2mL)中。向其中加入醋酸(0.1mL)和锌粉(200mg)并将所得的混合物声处理1小时。向其中加入另外的锌粉(100mg)并继续进行1小时声处理。将该反应混合物用二氧化硅过滤(500mg)并将其蒸发至干燥。向其中加入1，2-二氯乙烷(1mL)，然后向其中加入双光气(0.03mL)。将该反应混合物在室温下放置15分钟，然后将其加热至80℃加热3小时。在冷却至室温后，向其中加入三乙胺(0.12mL)。将所得混合物的等分试样(四分之一)与硫代乙醇(0.026mL)进行混合并将所得的混合物在室温下振荡一整夜。将该混合物蒸发至干燥，将其溶解于二甲基亚砜(0.2mL)中并用制备LC-MS对其进行处理，得到7.6mg标题化合物。收率：52％。(3-Benzyloxy-4-nitrophenyl)(4-fluorobenzyl)methylamine (50 mg) was dissolved in tetrahydrofuran (2 mL). To this was added acetic acid (0.1 mL) and zinc powder (200 mg) and the resulting mixture was sonicated for 1 hour. Additional zinc powder (100 mg) was added and sonication continued for 1 hour. The reaction mixture was filtered through silica (500 mg) and evaporated to dryness. 1,2-Dichloroethane (1 mL) was added thereto, and then diphosgene (0.03 mL) was added thereto. The reaction mixture was left at room temperature for 15 minutes, then it was heated to 80° C. for 3 hours. After cooling to room temperature, triethylamine (0.12 mL) was added thereto. An aliquot (one quarter) of the resulting mixture was mixed with thioethanol (0.026 mL) and the resulting mixture was shaken overnight at room temperature. The mixture was evaporated to dryness, dissolved in dimethyl sulfoxide (0.2 mL) and processed by preparative LC-MS to afford 7.6 mg of the title compound. Yield: 52%.

LC-MS(m/z)425.2([M+H]+)；RT＝3.35，(UV，ELSD)95％，99％。LC-MS (m/z) 425.2 ([M+H] + ); RT = 3.35, (UV, ELSD) 95%, 99%.

由适宜的硝基化合物和亲核试剂相似地制备下面的化合物：The following compounds were similarly prepared from the appropriate nitro compound and nucleophile:

12b{2-环戊氧基-4-[(4-氟苄基)-(甲基)氨基]-苯基}-硫代氨基甲酸S-乙酯12b{2-Cyclopentyloxy-4-[(4-fluorobenzyl)-(methyl)amino]-phenyl}-thiocarbamic acid S-ethyl ester

LC-MS(m/z)403.1([M+H]+)；RT＝3.30，(UV，ELSD)99％，100％。LC-MS (m/z) 403.1 ([M+H] + ); RT = 3.30, (UV, ELSD) 99%, 100%.

12c 1-{2-环戊氧基-4-[(4-氟苄基)-(甲基)氨基]-苯基}-3-乙基-脲12c 1-{2-cyclopentyloxy-4-[(4-fluorobenzyl)-(methyl)amino]-phenyl}-3-ethyl-urea

用乙胺代替硫代乙醇。Ethylamine was used instead of thioethanol.

LC-MS(m/z)386.2([M+H]+)；RT＝2.08，(UV，ELS9)97％，100％。LC-MS (m/z) 386.2 ([M+H] + ); RT = 2.08, (UV, ELS9) 97%, 100%.

实施例13Example 13

13a N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(4氯苯基)-乙酰胺13a N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4 chlorophenyl)-acetamide

将2-氯-N(4)-(5-氯-噻吩-2-基甲基)-N(4)-甲基-苯-1，4-二胺(100mg)加入到位于橡胶盖的玻璃小瓶中的4-氯苯基乙酰氯(69mg)在无水乙腈(2mL)中的溶液中。将该反应混合物在微波装置中加热至150℃加热15分钟。将该反应混合物倾倒到饱和碳酸氢钠水溶液(5mL)中并用乙酸乙酯(5mL)进行萃取。将有机相用水(5mL)和盐水(5mL)进行洗涤，用硫酸钠进行干燥，过滤并将其蒸发至干燥。将该粗品用闪柱色谱纯化(用庚烷/乙酸乙酯梯度洗脱)，得到25.2mg标题化合物。收率：16％。2-Chloro-N(4)-(5-chloro-thiophen-2-ylmethyl)-N(4)-methyl-benzene-1,4-diamine (100 mg) was added to the glass A solution of 4-chlorophenylacetyl chloride (69 mg) in anhydrous acetonitrile (2 mL) in a vial. The reaction mixture was heated to 150° C. for 15 minutes in a microwave apparatus. The reaction mixture was poured into saturated aqueous sodium bicarbonate (5 mL) and extracted with ethyl acetate (5 mL). The organic phase was washed with water (5 mL) and brine (5 mL), dried over sodium sulfate, filtered and evaporated to dryness. The crude product was purified by flash column chromatography (gradient elution with heptane/ethyl acetate) to afford 25.2 mg of the title compound. Yield: 16%.

LC-MS(m/z)441.2([M+2]+)；RT＝3.83，(UV，ELSD)91％，99％。LC-MS (m/z) 441.2 ([M+2] + ); RT = 3.83, (UV, ELSD) 91%, 99%.

类似地制备下面的化合物(2-苯基丙酰氯是通过将2-苯基丙酸在亚硫酰氯中进行加热，随后蒸发来进行制备的)：The following compounds were prepared analogously (2-phenylpropanoyl chloride was prepared by heating 2-phenylpropanoic acid in thionyl chloride followed by evaporation):

13b N-{2-氯-4-[(5-氯-噻吩-2-基甲基)-(甲基)氨基]-苯基}-2-(4-氯苯基)-丙酰胺13b N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-chlorophenyl)-propionamide

LC-MS(m/z)453.0(M+)；RT＝4.01，(UV，ELSD)91％，99％。LC-MS (m/z) 453.0 (M + ); RT = 4.01, (UV, ELSD) 91%, 99%.

实施例14Example 14

14a{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-碘苯基}-氨基甲酸乙酯。14a {4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-iodophenyl}-carbamate ethyl ester.

将(4-氨基-2-碘苯基)-氨基甲酸乙酯(2.3g)和5-氯-噻吩-2-甲醛(1.15g)溶解于甲醇(8mL)中并将其在密封的玻璃管中在微波辐射线加热至130℃加热3分钟。在冷却至室温后，向其中加入氰基硼氢化钠(4.7g)在甲醇(10mL)中的溶液并将所得的混合物在密封的玻璃管中在微波辐射下加热至130℃加热5分钟。在冷却至室温后，将该混合物倾倒到水(50mL)中并用乙酸乙酯(50mL)进行萃取。将水相用乙酸乙酯(50mL)进行萃取并将所合并的有机相用水(80mL两次)和盐水(80mL两次)进行洗涤。将有机相用硫酸镁干燥，过滤并在真空下除去溶剂。将所得的油状物用闪柱色谱纯化(硅胶，用庚烷/乙酸乙酯梯度洗脱)。将所得产物由二噁烷/水冻干，得到橙色固体形式的标题化合物(2g，63％)。(4-Amino-2-iodophenyl)-ethylcarbamate (2.3 g) and 5-chloro-thiophene-2-carbaldehyde (1.15 g) were dissolved in methanol (8 mL) and placed in a sealed glass tube In the microwave radiation heating to 130 ℃ heating for 3 minutes. After cooling to room temperature, a solution of sodium cyanoborohydride (4.7 g) in methanol (10 mL) was added thereto and the resulting mixture was heated to 130° C. under microwave irradiation for 5 minutes in a sealed glass tube. After cooling to room temperature, the mixture was poured into water (50 mL) and extracted with ethyl acetate (50 mL). The aqueous phase was extracted with ethyl acetate (50 mL) and the combined organic phases were washed with water (twice 80 mL) and brine (twice 80 mL). The organic phase was dried over magnesium sulfate, filtered and the solvent was removed under vacuum. The resulting oil was purified by flash column chromatography (silica gel, gradient elution with heptane/ethyl acetate). The resulting product was lyophilized from dioxane/water to afford the title compound (2 g, 63%) as an orange solid.

1H NMR(CDCl3)：1.31(t，3H)，4.02(b，1H)，4.21(q，2H)，4.35(d，2H)，6.53(b，1H)，6.63(dd，1H)，6.75(s，2H)，7.06(d，1H)，7.63(bs，1H)。 1 H NMR (CDCl 3 ): 1.31(t, 3H), 4.02(b, 1H), 4.21(q, 2H), 4.35(d, 2H), 6.53(b, 1H), 6.63(dd, 1H), 6.75 (s, 2H), 7.06 (d, 1H), 7.63 (bs, 1H).

类似地制备下面的化合物：The following compounds were prepared analogously:

14b N-{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-碘苯基}-2-(4-氟苯基)-乙酰胺。14b N-{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-iodophenyl}-2-(4-fluorophenyl)-acetamide.

1H NMR(CDCl3)：3.72(s，2H)，4.01(b9 1H)，4.35(d，2H)，6.62(dd，1H)，6.75(s，2H)，7.00(d，1H)，7.09-7.12(m，3H)，7.35(dd，2H)，7.85(d，1H)。 1 H NMR (CDCl 3 ): 3.72(s, 2H), 4.01(b9 1H), 4.35(d, 2H), 6.62(dd, 1H), 6.75(s, 2H), 7.00(d, 1H), 7.09 -7.12 (m, 3H), 7.35 (dd, 2H), 7.85 (d, 1H).

实施例15Example 15

N-{5-[(5-氯-噻吩-2-基甲基)-氨基]-4′-二甲基氨基-联苯-2-基}-2-(4-氟苯基)-乙酰胺。N-{5-[(5-chloro-thiophen-2-ylmethyl)-amino]-4'-dimethylamino-biphenyl-2-yl}-2-(4-fluorophenyl)-ethyl amides.

将{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-碘苯基}-氨基甲酸乙酯(270mg)、4-二甲基氨基苯基硼酸(445mg)、和醋酸钯(II)(约10mg)混悬于丙酮(5mL)中。向其中加入碳酸钾(0.54mL，5M水溶液)并将该混合物在密封的玻璃管中在微波合成器中在125℃下加热10分钟。在冷却至室温后，t将有机相分离出来，将其在硅胶上蒸发，并将其用闪柱色谱处理三次(用庚烷/乙酸乙酯梯度洗脱)。将所得的固体用乙腈重结晶三次，得到38mg无色固体形式的标题化合物。将所合并的母液在硅胶上蒸发并将其用闪柱色谱进行处理。将所得的产物用甲醇重结晶，得到第二个产量(12mg)，将其与第一次产量合并，一共得到50mg(19％)标题化合物。{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-iodophenyl}-carbamic acid ethyl ester (270mg), 4-dimethylaminophenylboronic acid (445mg), and palladium(II) acetate (about 10 mg) were suspended in acetone (5 mL). Potassium carbonate (0.54 mL, 5M in water) was added and the mixture was heated in a sealed glass tube at 125° C. for 10 minutes in a microwave synthesizer. After cooling to room temperature, the organic phase was separated, evaporated on silica gel and flash-chromatographed three times (gradient elution with heptane/ethyl acetate). The resulting solid was recrystallized three times from acetonitrile to obtain 38 mg of the title compound as a colorless solid. The combined mother liquors were evaporated on silica gel and subjected to flash chromatography. The resulting product was recrystallized from methanol to give a second yield (12 mg) which was combined with the first yield to give a total of 50 mg (19%) of the title compound.

1H NMR(DMSO-d6)：2.91(s，6H)，3.44(s，2H)，4.39(d，2H)，6.32(t，1H)，6.51(dd，2H)，6.61(d，2H)，6.93(dd，2H)，7.02-7.04(m，3H)，7.07-7.10(m，2H)，7.22-7.23(m，2H)，9.01(s，1H)。 1 H NMR (DMSO-d 6 ): 2.91(s, 6H), 3.44(s, 2H), 4.39(d, 2H), 6.32(t, 1H), 6.51(dd, 2H), 6.61(d, 2H ), 6.93 (dd, 2H), 7.02-7.04 (m, 3H), 7.07-7.10 (m, 2H), 7.22-7.23 (m, 2H), 9.01 (s, 1H).

LC-MS(m/z)494.2(M+)；RT＝2.50，(UV，ELSD)95％，99％。LC-MS (m/z) 494.2 (M + ); RT = 2.50, (UV, ELSD) 95%, 99%.

实施例16Example 16

16a {4-[(5-氯-噻吩-2-基甲基)-氨基j-2-喹啉-3-基-苯基}-氨基甲酸乙酯16a {4-[(5-Chloro-thiophen-2-ylmethyl)-amino-2-quinolin-3-yl-phenyl}-urethane

将{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-碘苯基}-氨基甲酸乙酯(15mg)、3-喹啉硼酸(29.7mg)、醋酸钯(II)(约1mg)、碳酸钾(0.035mL，5M水溶液)、和丙酮(2mL)进行混合并将其在密封的管中在微波合成器中在125℃下加热10分钟，将该反应混合物用乙酸乙酯(4mL)进行萃取，将有机相用水(2×2mL)和盐水(2×2mL)进行洗涤，用硫酸镁干燥，过滤。在真空下除去溶剂，将粗品用制备LC-MS纯化。将所收集的级分真空蒸发，将其重新溶解于乙酸乙酯(5mL)中，将有机相用饱和碳酸氢钠水溶液(3mL)、水(3mL)和盐水(2×2mL)进行洗涤。将有机相用硫酸镁干燥，过滤并在真空下除去溶剂，得到标题化合物(5mg，33％)。{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-iodophenyl}-carbamic acid ethyl ester (15 mg), 3-quinolineboronic acid (29.7 mg), palladium acetate ( II) (ca. 1 mg), potassium carbonate (0.035 mL, 5M in water), and acetone (2 mL) were mixed and heated in a sealed tube at 125° C. for 10 minutes in a microwave synthesizer, and the reaction mixture was washed with Extracted with ethyl acetate (4 mL), the organic phase was washed with water (2 x 2 mL) and brine (2 x 2 mL), dried over magnesium sulfate and filtered. The solvent was removed under vacuum and the crude product was purified by preparative LC-MS. The collected fractions were evaporated in vacuo, redissolved in ethyl acetate (5 mL), and the organic phase was washed with saturated aqueous sodium bicarbonate (3 mL), water (3 mL) and brine (2 x 2 mL). The organic phase was dried over magnesium sulfate, filtered and the solvent was removed in vacuo to give the title compound (5 mg, 33%).

LC-MS(m/z)438.0([M+H]+)；RT＝2.32，(UV，ELSD)89％，100％。LC-MS (m/z) 438.0 ([M+H] + ); RT = 2.32, (UV, ELSD) 89%, 100%.

相似地制备下面的化合物：The following compounds were similarly prepared:

16b{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-吡啶-3-基-苯基}-氨基甲酸乙酯16b{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-pyridin-3-yl-phenyl}-urethane

LC-MS(m/z)388.2([M+H]+)；RT＝2.01，(UV，ELSD)97％，100％。LC-MS (m/z) 388.2 ([M+H] + ); RT = 2.01, (UV, ELSD) 97%, 100%.

16c {4-[(5-氯-噻吩-2-基甲基)-氨基]-2-吡啶-4-基-苯基}-氨基甲酸乙酯16c {4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-pyridin-4-yl-phenyl}-urethane

LC-MS(m/z)388.1([M+H]+)；RT＝1.95，(UV，ELSD)98％，100％。LC-MS (m/z) 388.1 ([M+H] + ); RT = 1.95, (UV, ELSD) 98%, 100%.

16d[4-[(5-氯-噻吩-2-基甲基)-氨基]-2-(6-甲氧基吡啶-3-基)-苯基]-氨基甲酸乙酯16d[4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-(6-methoxypyridin-3-yl)-phenyl]-urethane

LC-MS(m/z)418.3([M+H]+)；RT＝2.37，(UV，ELSD)79％，100％。LC-MS (m/z) 418.3 ([M+H] + ); RT = 2.37, (UV, ELSD) 79%, 100%.

16e{4-[(5-氯-噻吩-2-基甲基)-氨基]-2-喹啉-5-基-苯基}-氨基甲酸乙酯16e{4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-quinolin-5-yl-phenyl}-urethane

LC-MS(m/z)430.8([M+H]+)；RT＝2.13，(UV，ELSD)79％，99％。LC-MS (m/z) 430.8 ([M+H] + ); RT = 2.13, (UV, ELSD) 79%, 99%.

体外和体内试验In vitro and in vivo tests

已经对本发明的化合物进行了试验并且其在-种或多种下面的模型中表现出了作用。Compounds of the invention have been tested and shown to be effective in one or more of the following models.

通过KCNQ2通道的相对外向流量Relative outward flux through KCNQ2 channels

其对-种用于对本发明的化合物进行评估的KCNQ2筛选方案进行了举例说明。这种试验测量了通过KCNQ2通道的相对外向流量，并且其是在具有下述改变的情况下根据Tang等人(Tang W.等人，J.Biomol.Scree77.2001，6，325-331)所述的用于hERG钾通道的方法来进行的。It exemplifies a KCNQ2 screening protocol for evaluating compounds of the invention. This assay measures the relative outward flux through the KCNQ2 channel and is based on Tang et al. (Tang W. et al., J.Biomol.Scree77.2001, 6, 325-331) with the This was done as described for the hERG potassium channel.

在实验当天，将足够数目的稳定表达电压-门控KCNQ2通道的CHO细胞以足以产生单-融合层的密度进行涂镀。在试验前-天将这些细胞进行接种并将其用1μCi/ml[86Rb]负载一整夜。在实验的当天，将这些细胞用包含HBSS-的缓冲剂进行洗涤。将这些细胞用药物预培养30分钟并在再连续存在30分钟药物的情况下用15mM KCl的次最大浓度刺激该86Rb+外向流量。在培养适宜的时期后，取出上清液并将其在液体闪烁计数器(Tricarb)中进行计数。将细胞用2mM NaOH溶解并对86Rb+数量进行计数。计算相对外向流量((CPM上清液/(CPM上清液+CPM细胞))C化合物/(CPM上清液/(CPM上清液+CPM细胞))15nM KCl)*100-100。On the day of the experiment, sufficient numbers of CHO cells stably expressing voltage-gated KCNQ2 channels were plated at a density sufficient to generate mono-confluent layers. These cells were plated one day before the assay and loaded with 1 μCi/ml [ 86 Rb] overnight. On the day of the experiment, the cells were washed with HBSS-containing buffer. The cells were pre-incubated with drug for 30 minutes and the 86 Rb + efflux was stimulated with a submaximal concentration of 15 mM KCl in the presence of drug for another 30 minutes. After an appropriate period of incubation, the supernatant was removed and counted in a liquid scintillation counter (Tricarb). Cells were lysed with 2mM NaOH and the number of86Rb + was counted. Relative outward flux was calculated ((CPM supernatant /(CPM supernatant +CPM cells ))C compound /(CPM supernatant /(CPM supernatant +CPM cells )) 15nM KCl )*100-100.

本发明的化合物具有小于20000nM的EC50，其EC50在大多数情况中小于2000nM并且在许多情况中小于200nM。因此，认为本发明的化合物可用于治疗与KCNQ族钾通道有关的疾病。The compounds of the invention have an EC50 of less than 20000 nM, with an EC50 of less than 2000 nM in most cases and less than 200 nM in many cases. Accordingly, the compounds of the present invention are considered useful in the treatment of diseases associated with the KCNQ family of potassium channels.

电生理学膜片箝记录。Electrophysiological patch clamp recordings.

用常规的膜片箝记录技术在全细胞膜片箝构型中记录得自哺乳动物CHO细胞的电压-活化的KCNQ2电流(Hamill OP等人，Pflgers Arch1981；391：85-100)。使具有稳定表达的电压活化的KCNQ2通道的细胞在CO2培育器中在正常的细胞培养条件下进行生长并在涂镀后1-7天用其进行电生理学记录。通过将电压以5-20mV的增量(或者用斜坡方案(ramp protocol))从-100mV至-40mV的膜保持电位逐步增加至+80mV来激活KCNQ2钾通道(Tatulian L等人，J Neuroscience2001；21(15)：5535-5545)。在该电压-活化的KCNQ2电流的各种参数的基础上对这些化合物所诱导的电生理学作用进行评估。尤其是对其对该电流的活化阈值和对所诱导的最大电流的作用进行了研究。Voltage-activated KCNQ2 currents from mammalian CHO cells were recorded in a whole-cell patch-clamp configuration using conventional patch-clamp recording techniques (Hamill OP et al., Pflgers Arch 1981; 391:85-100). Cells with stably expressed voltage-activated KCNQ2 channels were grown under normal cell culture conditions in a CO 2 incubator and used for electrophysiological recordings 1-7 days after plating. The KCNQ2 potassium channel was activated by stepwise increasing the voltage in 5-20 mV increments (or with a ramp protocol) from a membrane holding potential of -100 mV to -40 mV to +80 mV (Tatulian L et al., J Neuroscience 2001; 21 (15): 5535-5545). The electrophysiological effects induced by these compounds were evaluated on the basis of various parameters of the voltage-activated KCNQ2 current. In particular, its activation threshold for this current and its effect on the maximum current induced was investigated.

已经在这种试验中对一些本发明的化合物进行了研究。认为该活化阈值左移或者所诱导的最大钾电流增加降低了神经元网络中的活性，从而使得这些化合物可用于神经元活性增加的疾病如癫痫。Several compounds of the invention have been studied in this assay. A leftward shift of this activation threshold or an induced increase in maximal potassium current is believed to reduce activity in neuronal networks, making these compounds useful in diseases in which neuronal activity is increased, such as epilepsy.

最大电休克max electric shock

本试验是在雄性小鼠组中用角膜电极进行的，在本试验中，给予0.4秒26mA的矩形波电流以诱导特征为后肢强直性伸展的惊厥(Wlaz等人，Epilepsy Research 1998，30，219-229)。The test was carried out with corneal electrodes in groups of male mice, in which a rectangular wave current of 26 mA was administered for 0.4 s to induce convulsions characterized by tonic extension of the hind limbs (Wlaz et al., Epilepsy Research 1998, 30, 219 -229).

毛果芸香碱诱导的癫痫发作Pilocarpine-induced seizures

毛果芸香碱诱导的癫痫发作是通过给雄性小鼠腹膜内注射毛果芸香碱(250mg/kg)来诱导的，并且对30分钟内导致姿势丧失的癫痫发作活性进行观察(Starr等人，PharmacologyBioclaemistny andBehavior 1993，45，321-325)Pilocarpine-induced seizures were induced by intraperitoneal injection of pilocarpine (250 mg/kg) into male mice and seizure activity leading to postural loss was observed within 30 min (Starr et al., Pharmacology Bioclaemistny and Behavior 1993, 45, 321 -325)

电癫痫发作-阈值试验Electrical Seizure-Threshold Test

用该往复方法(up-and-down method)的变型(Kimball等人，Radiation Research 1957，1-12)来测定诱导作为对雄性小鼠角膜电休克的响应的后肢强直性伸展的阈值中值。各组的第一只小鼠在14mA(0.4s，50Hz)下得到电休克并就其癫痫发作活性进行观察。如果观察到癫痫发作，则将下一只小鼠的电流降低1mA，但是，如果没有观察到癫痫发作，则将其电流增加1mA。对治疗组的15只小鼠都重复这种操作。A variation of this up-and-down method (Kimball et al., Radiation Research 1957, 1-12) was used to determine the median threshold for inducing tonic extension of the hindlimb in response to corneal electroshock in male mice. The first mouse of each group was electroshocked at 14 mA (0.4 s, 50 Hz) and observed for its seizure activity. If a seizure is observed, reduce the current to the next mouse by 1 mA, however, if no seizure is observed, increase its current by 1 mA. This operation was repeated for all 15 mice in the treatment group.

化学癫痫发作-阈值试验Chemical Seizure-Threshold Test

通过定时向各组雄性小鼠侧面尾静脉中输入戊四唑(5mg/ml，速率为0.5ml/分钟)来测定诱导阵挛性惊厥所需戊四唑的剂量阈值(Nutt等人，J Pharmacy and Pharmacology，1986，38，697-698)。The dose threshold of pentylenetetrazole needed to induce clonic convulsions was determined by timed infusion of pentylenetetrazole (5 mg/ml at a rate of 0.5 ml/min) into the lateral tail vein of male mice in each group (Nutt et al., J Pharmacy and Pharmacology, 1986, 38, 697-698).

扁桃体兴奋tonsil excitement

给大鼠进行手术，将三极电极植入到其背外侧扁桃体中。在手术后，使该动物恢复，然后使各组大鼠接受各种剂量的试验化合物或该药物的基质。在3-5周内，在每天+25μA的放电阈值后开始对动物进行刺激，并且注意各诱因癫痫发作的严重程度、癫痫发作的持续时间、和放电后电的持续时间。(Racine.Electroephalography andClinical Neurophysiology 1972，32，281-294)。Rats were operated on to have tripolar electrodes implanted in their dorsolateral tonsils. After surgery, the animals are allowed to recover, and groups of rats are then given various doses of the test compound or vehicle for the drug. Over a period of 3-5 weeks, animals were stimulated after a discharge threshold of +25 μA per day, and the severity of seizures, duration of seizures, and duration of post-discharge shocks were noted for each trigger. (Racine. Electroephalography and Clinical Neurophysiology 1972, 32, 281-294).

副作用side effect

通过测量小鼠仍然留在该rotarod装置上的时间来测量中枢神经系统副作用(Capacio等人，Drug and Chemical Toxicology 1992，15，177-201)；或者通过对越过试验笼子的红外光束的数目进行计数而测量其运动活性来对中枢神经系统副作用进行测定((Watson等人，Neuropharmacology 1997，36，1369-1375)。通过直肠探针或被植入的能测量温度的无线电遥测术发射器来测定所说化合物对动物核体温度的降温作用(Keeney等人，Physiology and Behaviour 2001，74，177-184。CNS side effects were measured by measuring the time the mouse remained on the rotarod device (Capacio et al., Drug and Chemical Toxicology 1992, 15, 177-201); or by counting the number of infrared beams passed over the test cage Central nervous system side effects are measured by measuring their locomotor activity ((Watson et al., Neuropharmacology 1997, 36, 1369-1375). All are measured by a rectal probe or implanted radiotelemetry transmitter capable of measuring temperature. Said the cooling effect of the compound on the temperature of animal nuclear body (Keeney et al., Physiology and Behavior 2001, 74, 177-184.

药动学Pharmacokinetics

通过i.v.和p.o.给药于Spraque Dawley大鼠，其后在20小时内取血样来测定所说化合物的药动学性质。血浆浓度是用LC/MS/MS来进行测定的。The pharmacokinetic properties of the compounds were determined by i.v. and p.o. administration to Spraque Dawley rats, after which blood samples were taken within 20 hours. Plasma concentrations were determined by LC/MS/MS.

Claims (36)

1. substituted general formula I right-diamino benzene derivant or its salt
Wherein
S is 0 or 1;
U is O, S, SO 2, SONR 11, CO-O or CONR 11Wherein
R 11Be selected from hydrogen, C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base, C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base; Or
R 2And R 11Form a kind of 1,2 or 3 saturated or undersaturated ring of other heteroatomic 5-8 person that randomly comprises together with its nitrogen-atoms that is attached thereto;
Q is 0 or 1;
X is CO or SO 2Prerequisite be when X be SO 2The time q be 0;
Z is O or S;
R 1Be selected from hydrogen, C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base, C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, acyl group, hydroxyl-C 1-6-alkane (alkene/alkynes) base, hydroxyl-C 3-8-cycloalkanes (alkene) base, hydroxyl-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, halo-C 1-6-alkane (alkene/alkynes) base, halo-C 3-8-cycloalkanes (alkene) base, halo-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, cyano group-C 1-6-alkane (alkene/alkynes) base, cyano group-C 3-8-cycloalkanes (alkene) base and cyano group-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base;
R 2Be selected from hydrogen, C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base, C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, Ar, Ar-C 1-6-alkane (alkene/alkynes) base, Ar-C 3-8-cycloalkanes (alkene) base, Ar-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, acyl group, hydroxyl-C 1-6-alkane (alkene/alkynes) base, hydroxyl-C 3-8-cycloalkanes (alkene) base, hydroxyl-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, halogen, halo-C 1-6-alkane (alkene/alkynes) base, halo-C 3-8-cycloalkanes (alkene) base, halo-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, cyano group, cyano group-C 1-6-alkane (alkene/alkynes) base, cyano group-C 3-8-cycloalkanes (alkene) base, cyano group-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, NR 10R 10 '-C 1-6-alkane (alkene/alkynes) base, NR 10R 10 '-C 3-8-cycloalkanes (alkene) base and NR 10R 10 '-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base; Wherein
R 10And R 10 'Be independently selected from hydrogen, C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base, C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, hydroxyl-C 1-6-alkane (alkene/alkynes) base, hydroxyl-C 3-8-cycloalkanes (alkene) base, hydroxyl-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, halo-C 1-6-alkane (alkene/alkynes) base, halo-C 3-8-cycloalkanes (alkene) base, halo-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, cyano group-C 1-6-alkane (alkene/alkynes) base, cyano group-C 3-8-cycloalkanes (alkene) base and cyano group-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, or
R 10And R 10 'Form a kind of 1,2 or 3 saturated or undersaturated ring of other heteroatomic 5-8 person that randomly comprises together with its nitrogen-atoms that is attached thereto;
Prerequisite is R 2When being halogen or cyano group, s is 0; With
Prerequisite be when s be 1 and R 2U is O or S when being hydrogen atom or acyl group;
R 3Be selected from C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base, heterocycle alkane (alkene) base, C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, C 1-6-alkane (alkene/alkynes) base-C 3-8-cycloalkanes (alkene) base, C 1-6-alkane (alkene/alkynes) base-heterocycle alkane (alkene) base, heterocycle alkane (alkene) base-C 1-6-alkane (alkene/alkynes) base, Ar, Ar-C 1-6-alkane (alkene/alkynes) base, Ar-C 3-8-cycloalkanes (alkene) base, Ar-heterocycle alkane (alkene) base, Ar-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, Ar-C 1-6-alkane (alkene/alkynes) base-C 3-8-cycloalkanes (alkene) base, Ar-C 1-6-alkane (alkene/alkynes) base-heterocycle alkane (alkene) base, C 1-6-alkane (alkene/alkynes) oxygen base-C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) oxygen base-C 1-6-alkane (alkene/alkynes) base, C 1-6-alkane (alkene/alkynes) oxygen base-C 3-8-cycloalkanes (alkene) base, C 1-6-alkane (alkene/alkynes) oxygen base-heterocycle alkane (alkene) base, Ar-oxygen base-C 1-6-alkane (alkene/alkynes) base, Ar-C 1-6-alkane (alkene/alkynes) oxygen base-C 1-6-alkane (alkene/alkynes) base, C 1-6-alkane (alkene/alkynes) oxygen base-carbonyl-C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) oxygen base-carbonyl-C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) oxygen base-carbonyl-C 1-6-alkane (alkene/alkynes) base, hydroxyl-C 1-6-alkane (alkene/alkynes) base, hydroxyl-C 3-8-cycloalkanes (alkene) base, hydroxyl-heterocycle alkane (alkene) base, hydroxyl-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, hydroxyl-C 1-6-alkane (alkene/alkynes) base-C 3-8-cycloalkanes (alkene) base, hydroxyl-C 1-6-alkane (alkene/alkynes) base-heterocycle alkane (alkene) base, halo-C 1-6-alkane (alkene/alkynes) base, halo-C 3-8-cycloalkanes (alkene) base, halo-heterocycle alkane (alkene) base, halo-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, halo-C 1-6-alkane (alkene/alkynes) base-C 3-8-cycloalkanes (alkene) base, halo-C 1-6-alkane (alkene/alkynes) base-heterocycle alkane (alkene) base, halo-C 1-6-alkane (alkene/alkynes) base-Ar, halo-C 3-8The basic Ar of-cycloalkanes (alkene), halo-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base-Ar, halo-C 1-6-alkane (alkene/alkynes) base-C 3-8-cycloalkanes (alkene) base-Ar, cyano group-C 1-6-alkane (alkene/alkynes) base, cyano group-C 3-8-cycloalkanes (alkene) base, cyano group-heterocycle alkane (alkene) base, cyano group-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, cyano group-C 1-6-alkane (alkene/alkynes) base-C 3-8-cycloalkanes (alkene) base, cyano group-C 1-6-alkane (alkene/alkynes) base-heterocycle alkane (alkene) base, acyl group-C 1-6-alkane (alkene/alkynes) base, acyl group-C 3-8-cycloalkanes (alkene) base, acyl group-heterocycle alkane (alkene) base, acyl group-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, acyl group-C 1-6-alkane (alkene/alkynes) base-C 3-8-cycloalkanes (alkene) base, acyl group-C 1-6-alkane (alkene/alkynes) base-heterocycle alkane (alkene) base, NR 12R 12 ', substituted NR randomly 12R 12 '-C 1-6-alkane (alkene/alkynes) base, substituted NR randomly 12R 12 '-C 3-8-cycloalkanes (alkene) base, substituted NR randomly 12R 12 '-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base; Wherein
R 12And R 12 'Be independently selected from hydrogen, C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base, C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, Ar, Ar-C 1-6-alkane (alkene/alkynes) base, Ar-C 3-8-cycloalkanes (alkene) base, Ar-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, Ar-heterocycle alkane (alkene) base, Ar-oxygen base-C 1-6-alkane (alkene/alkynes) base, Ar-oxygen base-C 3-8-cycloalkanes (alkene) base, Ar-oxygen base C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, Ar-oxygen base-heterocycle alkane (alkene) base, hydroxyl-C 1-6-alkane (alkene/alkynes) base, hydroxyl-C 3-8-cycloalkanes (alkene) base, hydroxyl-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, halo-C 1-6-alkane (alkene/alkynes) base, halo-C 3-8-cycloalkanes (alkene) base, halo-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, cyano group-C 1-6-alkane (alkene/alkynes) base, cyano group-C 3-8-cycloalkanes (alkene) base and cyano group-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, or
R 12And R 12 'Form a kind of 1,2 or 3 saturated or undersaturated ring of other heteroatomic 5-8 person that randomly comprises together with its nitrogen-atoms that is attached thereto;
With
The group of Y expression XXIV, XXV, XXVI, XXVII, XXVIII, XXXI or XXXXII:
Figure A2004800075070005C1
Or
Figure A2004800075070005C2
Wherein
This line is represented a kind of group shown in the Y to be connected to key on this carbon atom;
W is O or S;
V is N, C or CH;
T is N, NH or O;
A is 0,1,2 or 3;
B is 0,1,2,3 or 4;
C is 0 or 1;
D is 0,1,2 or 3;
E is 0,1 or 2;
F is 0,1,2,3,4 or 5;
G is 0,1,2,3 or 4;
H is 0,1,2 or 3;
J is 0,1 or 2;
K is 0,1,2 or 3; With
Each R 5Be independently selected from a C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base, C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, Ar, Ar-C 1-6-alkane (alkene/alkynes) base, Ar-C 3-8-cycloalkanes (alkene) base, Ar-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, Ar-oxygen base, Ar-oxygen base-C 1-6-alkane (alkene/alkynes) base, Ar-oxygen base-C 3-8-cycloalkanes (alkene) base, C 1-6-alkane (alkene/alkynes) base-heterocycle alkane (alkene) base, Ar-oxygen base-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, acyl group, C 1-6-alkane (alkene/alkynes) oxygen base, C 3-8-cycloalkanes (alkene) oxygen base, C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) oxygen base, C 1-6-alkane (alkene/alkynes) oxygen base-carbonyl, halogen, halo-C 1-6-alkane (alkene/alkynes) base, halo-C 3-8-cycloalkanes (alkene) base, halo-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base ,-CO-NR 6R 6 ', cyano group, cyano group-C 1-6-alkane (alkene/alkynes) base, cyano group-C 3-8-cycloalkanes (alkene) base, cyano group-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, NR 7R 7 ', S-R 8And SO 2R 8, or
Two R that adjoin 5Form a kind of one or two heteroatomic 5-8 person's ring that comprises with this aromatic group;
R 6And R 6 'Be independently selected from hydrogen, C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base, C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base and Ar;
R 7And R 7 'Be independently selected from hydrogen, C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base, C 3-8Cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, Ar, heterocycle alkane (alkene) base-C 1-6-alkane (alkene/alkynes) base, heterocycle alkane (alkene) base-C 3-8-cycloalkanes (alkene) base, heterocycle alkane (alkene) base-C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, heterocycle alkane (alkene) base-Ar and acyl group; Or
R 7And R 7 'Form a kind of 1,2 or 3 saturated or undersaturated ring of other heteroatomic 5-8 person that randomly comprises together with its nitrogen-atoms that is attached thereto; With
R 8Be selected from hydrogen, C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base, C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, Ar and-NR 9R 9 'R wherein 9And R 9 'Be independently selected from hydrogen, C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base and C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base.
2. chemical compound as claimed in claim 1, wherein R 1Be C 1-6-alkane (alkene/alkynes) base or hydrogen atom.
3. as any described chemical compound among the claim 1-2, wherein s is 0.
4. as any described chemical compound among the claim 1-2, wherein s is 1.
5. chemical compound as claimed in claim 4, wherein U is an oxygen atom.
6. as any described chemical compound, wherein a R among the claim 1-5 2Be selected from hydrogen, C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base, Ar, Ar-C 1-6-alkane (alkene/alkynes) base, halogen, halo-C 1-6-alkane (alkene/alkynes) base and cyano group;
Prerequisite is to work as R 2When being halogen or cyano group, s is 0; With
Prerequisite be when s be 0 and R 2U is O or S when being hydrogen atom.
7. as any described chemical compound among the claim 1-6, wherein Z is an oxygen atom.
8. as any described chemical compound among the claim 1-6, wherein Z is a sulphur atom.
9. as any described chemical compound among the claim 1-8, wherein q is 0.
10. as any described chemical compound among the claim 1-8, wherein q is 1.
11. as any described chemical compound among the claim 1-10, wherein X is CO.
12. as any described chemical compound, wherein a R among the claim 1-11 3Be C 1-6-alkane (alkene/alkynes) base, C 3-8-cycloalkanes (alkene) base, C 3-8-cycloalkanes (alkene) base-C 1-6-alkane (alkene/alkynes) base, heterocycle alkane (alkene) base-C 1-6-alkane (alkene/alkynes) base, heterocycle alkane (alkene) base, Ar, Ar-C 1-6-alkane (alkene/alkynes) base, Ar-oxygen base-C 1-6-alkane (alkene/alkynes) base, Ar-C 1-6-alkane (alkene/alkynes) oxygen base-C 1-6-alkane (alkene/alkynes) base, C] 6-alkane (alkene/alkynes) oxygen base-carbonyl-Cl-alkane (alkene/alkynes) is basic, halo-C 1-6-alkane (alkene/alkynes) base, NR 12W2 ', substituted NR randomly 12R 12 '-C 1-6-alkane (alkene/alkynes) base and randomly substituted NR 12R 12 '-C 3-8-cycloalkanes (alkene) base.
13. chemical compound as claimed in claim 12, wherein R 12And R 12 'Be independently selected from hydrogen, C 1-6-alkane (alkene/alkynes) base and Ar.
14. as any described chemical compound among the claim 1-13, wherein Y is formula XXIV.
15. as any described chemical compound among the claim 1-13, wherein Y is formula XXV.
16. as any described chemical compound among the claim 14-15, wherein W is an oxygen atom.
17. as any described chemical compound among the claim 14-15, wherein W is a sulphur atom.
18. as any described chemical compound among the claim 1-13, wherein Y is formula XXVII.
19. as any described chemical compound among the claim 1-13, wherein Y is formula XXXXI.
20. chemical compound as claimed in claim 19, wherein V is a nitrogen-atoms.
21. chemical compound as claimed in claim 19, wherein V is CH.
22. as any described chemical compound among the claim 1-13, wherein Y is formula XXXXII.
23. chemical compound as claimed in claim 22, wherein T is a nitrogen-atoms.
24. chemical compound as claimed in claim 22, wherein T is an oxygen atom.
25. as any described chemical compound, wherein each R among the claim 1-24 5Be independently selected from C 1-6-alkane (alkene/alkynes) base, C 1-6-alkane (alkene/alkynes) base-heterocycle alkane (alkene) base, Ar, C 1-6-alkane (alkene/alkynes) oxygen base, Ar-oxygen base, C 1-6-alkane (alkene/alkynes) oxygen base-carbonyl, halogen, halo-C 1-6-alkane (alkene/alkynes) base, NR 7R 7 ', S-R 8And SO 2R 8, or
Two R that adjoin 5Form a kind of one or two heteroatomic 5-8 person's ring that randomly comprises with this aromatic group.
26. chemical compound as claimed in claim 25, wherein R 7And R 7 'All be C 1-6-alkane (alkene/alkynes) base.
27. chemical compound as claimed in claim 25, wherein R 8Be selected from C 1-6-alkane (alkene/alkynes) base and Ar.
28. as any described chemical compound among the claim 1-27, said chemical compound is selected from:
4-[(benzofuran-2-ylmethyl)-amino]-the 2-aminomethyl phenyl }-the carbamic acid propyl ester;
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-the 2-aminomethyl phenyl }-urethanes;
4-[(benzo [b] thiophene-2-ylmethyl)-amino]-the 2-aminomethyl phenyl }-urethanes;
2-methyl-4-[(5-phenyl-thiophene-2-ylmethyl)-amino]-phenyl }-urethanes;
[4-(4-isopropyl-benzylamino)-2-aminomethyl phenyl]-urethanes;
[4-(4-fluoro-benzylamino)-2-aminomethyl phenyl]-carbamic acid propyl ester;
(4-{[4-(4-chloro-benzenesulfonyl)-3-methyl-thiophene-2-ylmethyl]-amino }-the 2-aminomethyl phenyl)-the carbamic acid propyl ester;
4-[(5-methyl-thiophene-2-ylmethyl)-amino]-the 2-aminomethyl phenyl }-the carbamic acid propyl ester;
4-[(5-bromo-thiophene-2-ylmethyl)-amino]-the 2-aminomethyl phenyl }-the carbamic acid propyl ester;
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-the 2-aminomethyl phenyl }-the carbamic acid propyl ester;
4-[(benzo [b] thiophene-2-ylmethyl)-amino]-the 2-aminomethyl phenyl }-the carbamic acid propyl ester;
2-methyl-4-[(5-phenyl-thiophene-2-ylmethyl)-amino]-phenyl }-the carbamic acid propyl ester;
[4-(4-isopropyl-benzylamino)-2-aminomethyl phenyl]-carbamic acid propyl ester;
4-[(5-bromo-thiophene-2-ylmethyl)-amino]-the 2-chlorphenyl }-urethanes;
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-the 2-chlorphenyl }-urethanes;
4-[(benzo [b] thiophene-2-ylmethyl)-amino]-the 2-chlorphenyl }-urethanes;
[2-chloro-4-(4-isopropyl-benzylamino)-phenyl]-urethanes;
[2-chloro-4-(4-fluoro-benzylamino)-phenyl]-urethanes;
2-chloro-4-{[4-(4-chloro-benzenesulfonyl)-3-methyl-thiophene-2-ylmethyl]-amino }-phenyl)-the carbamic acid propyl ester;
4-[(5-methyl-thiophene-2-ylmethyl)-amino]-the 2-chlorphenyl }-the carbamic acid propyl ester;
4-[(5-bromo-thiophene-2-ylmethyl)-amino]-the 2-chlorphenyl }-the carbamic acid propyl ester;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-the carbamic acid propyl ester;
4-[(benzo [b] thiophene-2-ylmethyl)-amino]-the 2-chlorphenyl }-the carbamic acid propyl ester;
4-[(benzofuran-2-ylmethyl)-amino]-the 2-chlorphenyl }-the carbamic acid propyl ester;
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-the 2-cyano-phenyl }-urethanes;
(4-(benzo [b] thiophene-2-ylmethyl)-amino]-the 2-methoxyphenyl }-methyl carbamate;
4-[(5-bromo-thiophene-2-ylmethyl)-amino]-the 2-methoxyphenyl }-carbamic acid isopropyl ester;
4-[(4-fluoro-benzyl)-(methyl) amino]-the 2-methoxyphenyl }-the carbamic acid propyl ester;
[4-(benzo [b] thiophene-2-ylmethyl-(methyl) amino)-2-methoxyl group-phenyl]-carbamic acid propyl ester;
4-[(5-ammonia-thiophene-2-ylmethyl)-(methyl) amino]-2-methoxyl group-phenyl }-the carbamic acid propyl ester;
4-[(5-bromo-thiophene-2-ylmethyl)-(methyl) amino]-2-methoxyl group-phenyl }-the carbamic acid propyl ester;
2-methoxyl group-4-[methyl-(5-methyl-thiophene-2-ylmethyl)-amino]-phenyl }-the carbamic acid propyl ester;
The 4-[(4-luorobenzyl)-(methyl)-amino]-the 2-isopropyl phenyl }-urethanes;
[4-(3-luorobenzyl amino)-2-methoxyphenyl]-urethanes;
[4-(4-isopropyl benzyl amino)-2-methoxyphenyl]-urethanes;
2-methoxyl group-4-[(3-methylthiophene-2-ylmethyl)-amino]-phenyl }-urethanes;
[4-(2,4-difluorobenzyl amino)-2-methoxyphenyl]-urethanes;
[2-cyclopentyloxy-4-(4-methoxy-benzyl amino)-phenyl]-urethanes;
[2-cyclopentyloxy-4-(3-fluoro-2-methyl-benzyl amino)-phenyl]-urethanes;
[4-(3-fluoro-2-methyl-benzyl amino)-2-benzene ethoxyl phenenyl]-urethanes;
[2-benzyloxy-4-(3-fluoro-2-methyl-benzyl amino)-phenyl]-urethanes;
[2-benzyloxy-4-(4-methyl sulfane base benzylamino)-phenyl]-urethanes;
4-[(benzo [b] thiene-3-yl-methyl)-amino]-2-cyclopentyloxy phenyl }-urethanes;
[4-(3-fluoro-2-methyl-benzyl amino)-2-isopropyl phenyl]-urethanes;
[2-benzyloxy-4-(3-methoxy-benzyl amino)-phenyl]-urethanes;
4-[(benzo [1,3] dioxole-5-ylmethyl)-amino]-the 2-isopropyl phenyl }-urethanes;
4-[(5-bromo-thiophene-2-ylmethyl)-amino]-phenyl }-the carbamic acid propyl ester;
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-the carbamic acid propyl ester;
[2-cyano group-4-(4-isopropyl benzyl amino)-phenyl]-urethanes;
4-[(5-bromo-thiophene-2-ylmethyl)-(methyl) amino]-the 2-aminomethyl phenyl }-the carbamic acid propyl ester;
The 4-[(4-isopropyl benzyl)-(methyl) amino]-the 2-aminomethyl phenyl }-the carbamic acid propyl ester;
2-methyl-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl }-the carbamic acid propyl ester;
2-methyl-4-[methyl-(4-methyl sulfane base-benzyl)-amino]-phenyl }-the carbamic acid propyl ester;
4-[(4-tert-butyl-benzyl)-(methyl) amino]-the 2-chlorphenyl }-urethanes;
2-chloro-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl }-urethanes;
2-chloro-4-[methyl-(4-methyl sulfane base-benzyl)-amino]-phenyl }-urethanes;
4-[(5-bromo-thiophene-2-ylmethyl)-(methyl) amino]-the 2-chlorphenyl }-the carbamic acid propyl ester;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-the carbamic acid propyl ester;
4-[(4-tert-butyl-benzyl)-(methyl) amino]-the 2-chlorphenyl }-the carbamic acid propyl ester;
2-chloro-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl }-the carbamic acid propyl ester;
4-[(5-bromo-thiophene-2-ylmethyl)-(methyl) amino]-2-trifluoromethyl-phenyl } urethanes;
4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-2-trifluoromethyl-phenyl }-urethanes;
4-[(4-isopropyl-benzyl)-(methyl) amino]-2-trifluoromethyl-phenyl }-urethanes;
4-[(4-tert-butyl-benzyl)-(methyl) amino]-2-trifluoromethyl-phenyl }-urethanes;
4-[methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl }-urethanes;
4-[methyl-(4-methyl sulfane base-benzyl)-amino]-2-trifluoromethyl-phenyl }-urethanes;
4-[(5-bromo-thiophene-2-ylmethyl)-(methyl) amino]-2-trifluoromethyl-phenyl }-the carbamic acid propyl ester;
4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-2-trifluoromethyl-phenyl }-the carbamic acid propyl ester;
4-[(4-isopropyl-benzyl)-(methyl) amino]-2-trifluoromethyl-phenyl }-the carbamic acid propyl ester;
4-[(4-tert-butyl-benzyl)-(methyl) amino]-2-trifluoromethyl-phenyl }-the carbamic acid propyl ester;
4-[methyl-(4-trifluoromethyl-benzyl) amino]-2-trifluoromethyl-phenyl }-the carbamic acid propyl ester;
4-[methyl-(4-methyl sulfane base-benzyl)-amino]-2-trifluoromethyl-phenyl }-the carbamic acid propyl ester;
4-[(5-bromo-thiophene-2-ylmethyl)-(methyl) amino]-the 2-cyano-phenyl }-the carbamic acid propyl ester;
4-[(4-tert-butyl-benzyl)-(methyl) amino]-the 2-cyano-phenyl }-the carbamic acid propyl ester;
2-cyano group-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl }-the carbamic acid propyl ester;
2-bromo-4-[(5-bromo-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-the carbamic acid propyl ester;
2-bromo-4-[(5-bromo-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-the carbamic acid propyl ester;
2-bromo-4-[(4-isopropyl benzyl)-(methyl) amino]-phenyl }-the carbamic acid propyl ester;
2-bromo-4-[(4-tert-butyl-benzyl)-(methyl) amino]-phenyl }-the carbamic acid propyl ester;
2-bromo-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl }-the carbamic acid propyl ester;
[2-iodo-4-(4-isopropyl-benzylamino)-phenyl]-carbamic acid propyl ester;
[4-(4-tert-butyl-benzylamino)-2-iodophenyl]-carbamic acid propyl ester;
[2-iodo-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid propyl ester;
[2-iodo-4-(4-methyl sulfane base-benzylamino)-phenyl]-carbamic acid propyl ester;
2-iodo-4-[4-(4-methyl piperazine-1-yl)-benzylamino]-phenyl }-the carbamic acid propyl ester;
4-[(5-bromo-thiophene-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl }-urethanes;
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl }-urethanes;
[4-(4-tert-butyl-benzylamino)-2-trifluoromethyl-phenyl]-urethanes;
[4-(4-methyl sulfane base-benzylamino)-2-trifluoromethyl-phenyl]-urethanes;
4-[(5-bromo-thiophene-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl }-the carbamic acid propyl ester;
[4-(4-isopropyl benzyl amino)-2-trifluoromethyl-phenyl]-carbamic acid propyl ester;
[4-(4-tert-butyl-benzylamino)-2-trifluoromethyl-phenyl]-carbamic acid propyl ester;
[2-trifluoromethyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid propyl ester;
[4-(4-dimethylamino-benzylamino)-2-trifluoromethyl-phenyl]-carbamic acid propyl ester;
[4-(4-methyl sulfane base-benzylamino)-2-trifluoromethyl-phenyl]-carbamic acid propyl ester;
4-[(5-bromo-thiophene-2-ylmethyl)-amino]-the 2-cyano-phenyl }-the carbamic acid propyl ester;
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-the 2-cyano-phenyl }-the carbamic acid propyl ester;
[2-cyano group-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid propyl ester;
2-bromo-4-[(5-bromo-thiophene-2-ylmethyl)-amino]-phenyl }-the carbamic acid propyl ester;
2-bromo-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-the carbamic acid propyl ester;
[2-bromo-4-(4-isopropyl benzyl amino)-phenyl]-carbamic acid propyl ester;
[2-bromo-4-(4-tert-butyl-benzylamino)-phenyl]-carbamic acid propyl ester;
[2-bromo-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid propyl ester;
[2-bromo-4-(4-methyl sulfane base-benzylamino)-phenyl]-carbamic acid propyl ester;
N-{4-[(5-bromo-thiophene-2-ylmethyl)-amino]-the 2-methoxyphenyl }-butyramide;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-amino]-the 2-methoxyphenyl }-butyramide;
N-[4-(4-isopropyl benzyl amino)-2-methoxyphenyl]-butyramide;
N-[4-(4-tert-butyl-benzylamino)-2-methoxyphenyl]-butyramide;
N-[2-methoxyl group-4-(4-trifluoromethyl-benzylamino)-phenyl]-butyramide;
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-2-furan-2-base-phenyl }-the carbamic acid propyl ester;
[2-furan-2-base-4-(4-isopropyl benzyl amino)-phenyl]-carbamic acid propyl ester;
[5-(4-luorobenzyl amino)-xenyl-2-yl]-carbamic acid propyl ester;
5-[(5-chloro-thiophene-2-ylmethyl)-amino]-biphenyl-2-yl }-the carbamic acid propyl ester;
[5-(4-isopropyl benzyl amino)-biphenyl-2-yl]-carbamic acid propyl ester;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-the 2-phenyl-acetamides;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-3, the 3-amide dimethyl butyrate;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-the 3-Phenylpropionamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-butyramide;
Valeric acid 2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-amide;
Cyclopropane-carboxylic acid 2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-amide;
Cyclobutylcarboxylic acid 2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-amide;
Cyclopentane carboxylic acid 2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-amide;
Cyclohexane-carboxylic acid 2-chloro-4-[(5-chloro-thiophene-2-ylmethyl) (methyl) amino]-phenyl }-amide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-2-thiophene-2-base-acetamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-2-(3-methoxyl group-phenyl)-acetamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-2-(4-chloro-phenyl)-acetamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-2-(4-methoxyl group-phenyl)-acetamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-2-(4-fluoro-phenyl)-acetamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-3-cyclohexyl propionic acid amide.;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-2,2-dimethyl propylene amide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-the 2-phenoxy-acetamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-the 2-phenyl-acetamides;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-3, the 3-amide dimethyl butyrate;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-butyramide;
Valeric acid 2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-amide;
Cyclopropane-carboxylic acid 2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-amide;
Cyclobutylcarboxylic acid 2-chloro-4-((5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-amide;
Cyclopentane carboxylic acid 2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-amide;
Cyclohexane-carboxylic acid 2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-amide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-2-thiophene-2-base-acetamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-2-(3-methoxyphenyl)-acetamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-2-(4-chlorphenyl)-acetamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-2-(4-methoxyphenyl)-acetamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-2-(4-fluorophenyl)-acetamide;
2,3-dihydro-benzo [1,4] dioxine-6-formic acid 2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-amide;
2,3-dihydro-benzofuran-5-formic acid 2-chloro-4-[(5-chloro-thiophene-2 ylmethyl)-amino]-phenyl }-amide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-3-cyclohexyl propionic acid amide.;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-2-methyl-phenyl }-2,2-dimethyl propylene amide;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-2-methyl-phenyl }-the 2-phenyl-acetamides;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-2-methyl-phenyl }-3, the 3-amide dimethyl butyrate;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-2-methyl-phenyl }-the 3-Phenylpropionamide;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-2-methyl-phenyl }-butyramide;
2,2,2-three chloro-N-{4-[(5-chloro-thiophene-2-ylmethyls)-(methyl) amino]-2-methyl-phenyl }-acetamide;
Cyclopropane-carboxylic acid 4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-2-methyl-phenyl }-amide;
Cyclobutylcarboxylic acid 4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-the 2-aminomethyl phenyl }-amide;
Cyclopentane carboxylic acid 4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-the 2-aminomethyl phenyl }-amide;
Cyclohexane-carboxylic acid 4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-the 2-aminomethyl phenyl }-amide;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-the 2-aminomethyl phenyl }-2-thiophene-2-base-acetamide;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-the 2-aminomethyl phenyl }-2-(3-methoxyphenyl)-acetamide;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-the 2-aminomethyl phenyl }-the malonamic acid methyl ester;
2-(4-chlorphenyl)-N-{4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-the 2-aminomethyl phenyl }-acetamide;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-the 2-aminomethyl phenyl }-2-(4-methoxyl group phenoxy group)-acetamide;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-the 2-aminomethyl phenyl }-2-(4-fluorophenyl)-acetamide;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-the 2-aminomethyl phenyl }-3-cyclohexyl propionic acid amide.;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-phenyl carbamate;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-benzyq carbamate;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-isobutyl carbamate;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-butyl carbamate;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-the own ester of carbamic acid;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-carbamic acid 4-nitrobenzyl ester;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-carbamic acid fourth-3-alkene ester;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-carbamic acid fourth-2-alkynes ester;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-carbamic acid 2,2-dimethyl propyl ester;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-carbamic acid 2-benzyl chloride ester;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-carbamic acid 3-chlorine propyl ester;
2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-carbamic acid 2-benzyloxy ethyl ester;
3-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-1-methyl isophthalic acid-propyl group-urea;
1-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-3-(2-fluorophenyl)-urea;
N-[2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-2,2, the 2-trifluoroacetamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-amino]-phenyl }-2,2, the 2-trifluoroacetamide;
N-{5-[(5-chloro-thiophene-2-ylmethyl) amino]-4 '-dimethylamino-biphenyl-2-yl }-2-(4-fluorophenyl)-acetamide;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-2-(4-chlorphenyl)-acetamide;
[4-(3-fluoro-4-trifluoromethyl-benzylamino)-2-aminomethyl phenyl]-urethanes;
2-(4-fluorophenyl)-N-{2-methyl-4-[(6-p-toloxyl pyridin-3-yl methyl)-amino]-phenyl }-acetamide;
N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-butyramide;
2-(4-fluorophenyl)-N-{2-methyl-4-[(6-5-flumethiazine-3-ylmethyl)-amino]-phenyl 2-acetamide;
Valeric acid 4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-the 2-aminomethyl phenyl }-amide;
3,3-dimethyl-N-{2-methyl-4-[(6-is right-toloxyl pyridin-3-yl methyl)-amino]-phenyl }-butyramide;
[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-urethanes;
N-{2-chloro-4-[(5-chloro-thiophene-2-ylmethyl)-(methyl) amino]-phenyl }-2-(4-chlorphenyl)-propionic acid amide.;
[4-(4-chloro-benzylamino)-2-aminomethyl phenyl]-urethanes;
4-[(6-methoxyl group-benzo [b] thiophene-2-ylmethyl)-amino]-the 2-aminomethyl phenyl }-the carbamic acid propyl ester;
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-2-quinoline-3-base-phenyl }-urethanes;
4-[(5-dimethylamino-3-methyl-benzo [b] thiophene-2-ylmethyl)-amino]-the 2-aminomethyl phenyl }-the carbamic acid propyl ester;
3,3-dimethyl-N-{2-methyl-4-[(6-5-flumethiazine-3-ylmethyl)-amino]-phenyl }-] butyramide;
N-(4-{[6-(4-cyano-benzene oxygen)-pyridin-3-yl methyl]-amino }-the 2-aminomethyl phenyl)-2-(4-fluorophenyl)-acetamide;
2-benzyloxy-4-[(4-luorobenzyl)-(methyl) amino]-phenyl }-S-ethyl thiocarbamate;
2-cyclopentyloxy-4-[(4-luorobenzyl)-(methyl) amino]-phenyl }-S-ethyl thiocarbamate;
N-{4-[(6-chloropyridine-3-ylmethyl)-amino]-the 2-aminomethyl phenyl }-2-(4-fluorophenyl)-acetamide;
4-[(7-dimethylamino-benzo [b] thiophene-2-ylmethyl) amino]-the 2-aminomethyl phenyl }-the carbamic acid propyl ester;
1-{2-cyclopentyloxy-4-[(4-luorobenzyl)-(methyl) amino]-phenyl }-3-ethyl-urea;
2-amino-4-methyl-valeric acid [2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-amide;
4-[(6-methoxyl group-benzo [b] thiophene-2-ylmethyl)-amino]-the 2-aminomethyl phenyl }-urethanes;
2-amino-4-methyl-valeric acid [2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-amide;
2-(4-fluorophenyl)-N-{2-methyl-4-[(4-methyl-2-phenyl pyrimidine-5-ylmethyl)-amino]-phenyl }-acetamide;
3,3-dimethyl-N-{2-methyl-4-[(2-phenyl pyrimidine-5-ylmethyl)-amino]-phenyl }-butyramide;
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-2-pyridin-3-yl-phenyl }-urethanes;
1-amino-cyclopropane-carboxylic acid [2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-amide;
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-2-pyridin-4-yl-phenyl }-urethanes;
N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-piperidines-1-base-acetamide;
N-(4-{[5-(4-chlorophenoxy)-1,3-dimethyl-1H-pyrazoles-4-ylmethyl]-amino }-the 2-aminomethyl phenyl)-2,2-dimethyl propylene amide;
2,2-dimethyl-N-{2-methyl-4-[(6-phenoxypyridines-3-ylmethyl)-amino]-phenyl }-propionic acid amide.;
N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-pyrrolidine-1-base-acetamide;
[4-[(5-chloro-thiophene-2-ylmethyl)-amino]-2-(6-methoxypyridine-3-yl)-phenyl]-urethanes;
4-[(3-methyl-4-propoxycarbonyl amino-phenyl amino)-methyl]-essence of Niobe;
N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-morpholine-4-base-acetamide;
2,2-dimethyl-N-{2-methyl-4-[(3-methyl-5-phenyl-isoxazole azoles-4-ylmethyl)-amino]-phenyl }-propionic acid amide.;
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-the 2-iodophenyl }-urethanes;
N-{4-[(5-chloro-thiophene-2-ylmethyl)-amino]-the 2-iodophenyl-2-(4-fluorophenyl)-acetamide and
4-[(5-chloro-thiophene-2-ylmethyl)-amino]-2-quinoline-5-base-phenyl }-urethanes
Or its salt.
29. one kind comprises one or more pharmaceutically useful carriers or diluent and as the pharmaceutical composition of any described chemical compound among the claim 1-28.
30. pharmaceutical composition as claimed in claim 29 is used for increasing the application of ion flow of mammal such as people's potassium channel.
31. be used to prevent, treat or suppress the increase of potassium channel intermediate ion stream is had the application as claimed in claim 30 of the disease or the situation of response, such disease or situation be central nervous system's disease or situation preferably.
32. application as claimed in claim 31, wherein said disease or disease are selected from epilepsy disease such as convulsions, epilepsy and status epilepticus.
33. application as claimed in claim 31 is characterized in that said disease or situation are selected from neuropathic pain and migraine antalgesic such as allodynia, hyperpathia pain, phantom pain, the neuropathic pain relevant with diabetic neuropathy and the relevant neuropathic pain with migraine.
34. application as claimed in claim 31, it is characterized in that said disease or situation be selected from anxiety disorder such as anxiety, generalized-anxiety disorder, panic anxiety, obsession, social phobia, behavior anxiety, post-traumatic stress disorder, gross stress reaction, adjustment disorder, hypochondriacal disorder, separation anxiety disorder, agoraphobia, specific phobia, because anxiety disorder and the inductive anxiety disorder of material that general medical condition causes.
35. application as claimed in claim 31 is characterized in that said disease or situation are selected from neurodegenerative disorders such as Alzheimer, Huntington Chorea, multiple sclerosis, amyotrophic lateral sclerosis, the inductive encephalopathy of AIDS-and other and the neural degeneration that infects relevant encephalopathy, Creutzfeld-Jakob disease, parkinson, wound-induced that are caused by rubella virus, herpesvirus, Borrelia and unknown pathogen.
36. application as claimed in claim 31 is characterized in that said disease or situation are selected from the state in neuronal excitation transient state such as drug withdrawal or the poisoning.
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CN105017085A (en) * 2014-04-28 2015-11-04 中国科学院上海药物研究所 Novel KCNQ potassium channel agonist and preparation method and application thereof
US10077245B2 (en) 2014-04-28 2018-09-18 Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences KCNQ potassium channel agonists, method of preparation and method of use thereof
US10316008B2 (en) 2014-04-28 2019-06-11 Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences KCNQ potassium channel agonist, and preparation method therefor and use thereof
CN108707087A (en) * 2018-06-29 2018-10-26 河北医科大学 A kind of 4-（To trifluoromethyl benzyl）Fluoro- 1,2,4 triphenylamine derivatives of -3- and its pharmaceutical composition and purposes
WO2020001298A1 (en) * 2018-06-29 2020-01-02 河北医科大学 4-(p-trifluoromethylbenzyl)-3-floro-1,2,4 triphenylamine derivative, pharmaceutical composition of same, and uses thereof
CN108707087B (en) * 2018-06-29 2020-10-16 河北医科大学 4- (p-trifluoromethyl benzyl) -3-fluoro-1, 2,4 triphenylamine derivative, and pharmaceutical composition and application thereof
US11247966B2 (en) 2018-06-29 2022-02-15 Hebei Medical University 4-(p-trifluoromethylbenzyl)-3-fluoro-1,2,4-triphenylamine derivative and pharmaceutical composition and applications thereof

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NZ541945A (en) 2009-02-28
UA81019C2 (en) 2007-11-26
IS7991A (en) 2005-08-18
CL2004000575A1 (en) 2005-01-21

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