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WO2019048988A1 - NOVEL FUNGICIDE HETEROCYCLIC COMPOUNDS - Google Patents

NOVEL FUNGICIDE HETEROCYCLIC COMPOUNDS Download PDF

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Publication number
WO2019048988A1
WO2019048988A1 PCT/IB2018/056580 IB2018056580W WO2019048988A1 WO 2019048988 A1 WO2019048988 A1 WO 2019048988A1 IB 2018056580 W IB2018056580 W IB 2018056580W WO 2019048988 A1 WO2019048988 A1 WO 2019048988A1
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Prior art keywords
methyl
oxo
piperidin
acetyl
thiazole
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PCT/IB2018/056580
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French (fr)
Inventor
Gajanan SHANBHAG
Aditya Sharma
G. Renugadevi
Jagadish Pabba
Rohit Arvind DENGALE
Dipankar Roy
Mohan Kumar S.P.
Yogesh Kashiram BELKAR
Santosh Shridhar AUTKAR
Ruchi GARG
Hagalavadi M VENKATESHA
Alexander Guenther Maria KLAUSENER
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PI Industries Ltd
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PI Industries Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles

Definitions

  • the present invention relates to novel fungicidal heterocyclic compounds and its salts, metal complexes, N-oxides, enantiomers, stereoisomers and polymorphs thereof; compositions and methods of use of the compounds for controlling or preventing phytopathogenic micro-organisms.
  • the present invention relates to a compound selected from Formula I, wherein the substituents are as defined in the description.
  • compositions comprising, “comprising”, “includes”, “including”, “has”, “having”, “contains”, “containing”, “characterized by” or any other variation thereof, are intended to cover a nonexclusive inclusion, subject to any limitation explicitly indicated.
  • a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process or method.
  • Stereoisomers of the present invention may be present either in pure form or as mixtures of different possible isomeric forms such as stereoisomers or constitutional isomers.
  • the various stereoisomers include enantiomers, diastereomers, chiral isomers, atropisomers, conformers, rotamers, tautomers, optical isomers, polymorphs, and geometric isomers. Any desired mixtures of these isomers fall within the scope of the claims of the present invention.
  • one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other isomer(s) or when separated from the other isomer(s). Additionally, the person skilled in the art knows processes or methods or technology to separate, enrich, and/or to selectively prepare said isomers.
  • alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” or -N(alkyl) or alkylcarbonylalkyl or alkylsuphonylamino includes straight-chain or branched Cj to C 2 4 alkyl, preferably Ci to C ) 5 alkyl, more preferably Cj to C
  • alkyl include methyl, ethyl, propyl, 1 -methylethyl, butyl, 1 -methylpropyl, 2-methylpropyl, 1 , 1 -dimethyl ethyl, pentyl, 1 -methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1 - ethylpropyl, hexyl, 1 , 1 -dimethylpropyl, 1 ,2-dimethylpropyl, 1 -methylpentyl, 2-methylpentyl, 3- methylpentyl, 4-methylpentyI, 1 , 1 -dimethyl butyl, 1 ,2-dimethylbutyl, 1 ,3-dimethylbutyl, 2,2- dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1 -ethylbutyl, 2-ethylbutyl, 1
  • the alkyl is at the end of a composite substituent, as, for example, in alkylcycloalkyl
  • the part of the composite substituent at the start for example the cycloalkyl
  • other radicals for example alkenyl, alkynyl, hydroxyl, halogen, carbonyl, carbonyloxy and the like, are at the end.
  • alkenyl used either alone or in compound words includes straight-chain or branched C 2 to C 2 4 alkenes, preferably C 2 to C 15 alkenes, more preferably C 2 to C
  • alkenes include ethenyl, 1 -propenyl, 2-propenyl, 1 -methylethenyl, 1 -butenyl, 2-butenyl, 3-butenyl, 1 -methyl- 1 -propenyl, 2-methyl-l-propenyl, l-methyl-2 -propenyl, 2-methyl-2- propenyl, 1 -pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1 -methyl- 1 -butenyl, 2-methyl- l -buteny!, 3- methyl- l -butenyl, l-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, l-methyl-3-butenyl, 2- methyl-3-butenyl, 3-methyl-3-butenyl, l , l -dimethyl-2-propenyl, 1 ,2-dimethyl-l -buten
  • Alkenyl also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl . This definition also applies to alkenyl as a part of a composite substituent, for example haloalkeny! and the like, unless defined specifically elsewhere.
  • alkynyl used either alone or in compound words includes straight-chain or branched C 2 to C 24 alkynes, preferably C 2 to C , 5 alkynes, more preferably C 2 to C ]0 alkynes, most preferably C 2 to C f) alkynes.
  • alkynes include ethynyl, 1 -propynyl, 2-propynyl, 1 -butynyl, 2- butynyl, 3-butynyl, l -methyl-2-propynyl, 1 -pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, l-methyl-2- butynyl, l-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-l-butynyl, l , ] -dimethyl-2-propynyl, 1 -ethyl -
  • 2- propynyl 1 -hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, l -methyl-2-pentynyl, l-methyl-3- pentynyl, l -methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyI-4-pentynyl, 3-methyl-l-pentynyl, 3- methyl-4-pentynyl, 4-methyl-l-pentynyl, 4-methyl-2-pentynyl, l , l -dimethyl-2-butynyl, l,l-dimethyl-3- butynyl, l,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-l-butynyl, l-ethyl-2-butynyl,
  • alkynyl as a part of a composite substituent, for example haloalkynyl etc., unless specifically defined elsewhere.
  • Alkynyl can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.
  • cycloalkyl means alkyl closed to form a ring. Representative examples include but are not l imited to cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. This definition also applies to cycloalkyl as a part of a composite substituent, for example cycloalkylalkyl etc., unless specifically defined elsewhere.
  • cycloalkenyl means alkenyl closed to form a ring including monocyclic, partially unsaturated hydrocarbyl groups. Representative examples include but are not limited to cyclopentenyl and cyclohexenyl. This definition also applies to cycloalkenyl as a part of a composite substituent, for example cycloalkenylalkyl etc., unless specifically defined elsewhere.
  • cycloalkynyl means alkynyl closed to form a ring including monocyclic, partially unsaturated groups. This definition also applies to cycloalkynyl as a part of a composite substituent, for example cycloalkynylalkyl etc., unless specifically defined elsewhere.
  • cycloalkoxy cycloalkenyloxy
  • cycloalkoxy cycloalkenyloxy
  • Representative examples of cycloalkoxy include cyclopropyloxy, cyclopentyloxy and cyclohexyloxy. This definition also applies to cycloalkoxy as a part of a composite substituent, for example cycloalkoxy alkyl etc., unless specifically defined elsewhere.
  • halogen either alone or in compound words such as “haloalkyl”, includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, said alkyl may be partially or fully substituted with halogen atoms which may be the same or different.
  • haloalkyl include chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1 -chloroethyl, 1 -bromoethyl, 1 -fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2- fluoroethyl, 2,2,2-trichIoroethyl, pentafluoroethyl, 1 , l -dichloi -2,2,2-trifluoroethyl, and 1 , 1 , 1 - trifluoroprop-2-
  • haloalkenyl and "haloalkyny! are defined analogously except that, instead of alkyl groups, alkenyl and alkynyl groups are present as a part of the substituent.
  • haloalkoxy means straight-chain or branched alkoxy groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified 'above.
  • Non-limiting examples of haloalkoxy include chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fiuoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1 -chloroethoxy, 1 -bromoethoxy, 1 -fluoroethoxy, 2-fluoroethoxy, 2,2- difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloiO-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro- 2-fluoroethoxy, 2,2,2-trichloroethoxy, penta
  • haloalkylthio means straight-chain or branched alkylthio groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above.
  • Non-limiting examples of haloalkylthio include chloromethylthio, bromomethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio, dichlorofluoromethylthio, chlorodifiuoromethylthio, 1 -chloroethylthio, 1 -bromoethylthio, 1 - fluoroethylthio, 2-fluoroethylthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2-chloro-2- fluoroethylthio, 2-chloro-2,2-difluoro
  • haloalkylthio as a part of a composite substituent, for example haloalkylthioalkyl etc., unless specifically defined elsewhere.
  • haloalkylsulfinyl include CF 3 S(0), CC1 3 S(0), CF 3 CH 2 S(0) and CF 3 CF 2 S(0).
  • haloalkylsulfonyl include CF 3 S(0) 2 , CC1 3 S(0) 2 , CF 3 CH 2 S(0) 2 and CF 3 CF 2 S(0) 2 .
  • hydroxy means -OH
  • amino means -NRR, wherein R can be H or any possible substituent such as alkyl.
  • carbonyl means -C(O)-
  • carbonyloxy means -OC(O)-
  • sulfinyl means S(O)
  • sulfonyl means S(0) 2 '
  • alkoxy used either alone or in compound words included Cj to C 24 alkoxy, preferably C
  • alkoxy include methoxy, ethoxy, propoxy, 1 -methyl ethoxy, butoxy, 1 -methylpropoxy, 2-methylpropoxy, 1 , 1 - dimethylethoxy, pentoxy, 1 -methylbutoxy, 2-methylbutoxy, 3 -methyl butoxy, 2,2-dimethylpropoxy, 1 - ethylpropoxy, hexoxy, 1 , 1 -dimethylpropoxy, 1 ,2-dimethylpropoxy, 1 -methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methyl pentoxy, 1 , 1 -dimethylbutoxy, 1 ,2-dimethylbutoxy, 1 ,3-dimethylbutoxy, 2,2- dimethylbutoxy, 2,3-di
  • alkoxyalkyl means alkoxy substitution on alkyl .
  • alkoxyalkyl include CH 3 OCH 2 ; CH 3 OCH 2 CH 2 ; CH 3 CH 2 OCH 2 ; CH 3 CH 2 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • alkoxyalkoxy means alkoxy substitution on alkoxy.
  • alkylthio includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, propylthio, 1 -methylethylthio, butylthio, 1 -methylpropylthio, 2-methylpropylthio, 1 , 1 -dimethylethylthio, pentylthio, 1 -methylbiitylthio, 2-methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio, 1 - ethylpropylthio, hexylthio, 1 , 1 -dimethylpropylthio, 1 ,2-dimethylpropylthio, 1 -methylpentylthio, 2- methylpentylthio, 3-methylpentylthio, 4-methylpentylthio, 1 , 1 -dimethylbutylthio, 1 ,2-dimethylbutylthio
  • halocylcoalkyl halocylcoalkenyl
  • alkylcycloalkyl cycloalkylalkyl
  • cycloalkoxyalkyl alkylsulfinylalkyl
  • alkylsulfonylalkyl alkylsulfonylalkyl
  • haloalkylcarbonyl alkylcarbonyl
  • alkylthioalkyl means alkylthio substitution on alkyl.
  • alkylthioalkyl include CH 2 SCH 2 ; CH 2 SCH 2 CH 2 ; CH 3 CH 2 SCH 2 ; CH 3 CH 2 CH 2 CH 2 SCH 2 ; CH 3 CH 2 SCH 2 CH 2 and the like or different isomers.
  • alkylthioalkoxy denotes alkylthio substitution on alkoxy.
  • cycloalkylalkylamino denotes cycloalkyi substitution on alkyl amino.
  • alkoxyalkoxyalkyl is defined analogously to “alkylthioalkyl” or cycloalkylalkylamino.
  • alkoxycarbonyl is an alkoxy group bonded to a skeleton via a carbonyl group (-CO-). This definition also applies to alkoxycarbonyl as a part of a composite substituent, for example cycloalkylalkoxycarbonyl and the like, unless specifically defined elsewhere.
  • alkoxycarbonylalkylamino means alkoxy carbonyl substitution on alkyl amino.
  • alkylcarbonylalkylamino means alkyl carbonyl substitution on alkyl amino.
  • alkylthioalkoxycarbonyl, cycloalkylalkylaminoaikyl and the like are defined analogously.
  • alkylsulfinyl means alkyl substitution on sulfinyl group.
  • Non-l imiting examples of “alkylsu!finyl” include ; methylsulphinyl; ethylsulphinyl; propylsulphinyl; 1 -methylethylsulphinyl; butylsulphinyl ; 1 -methylpropylsulphinyl ; 2-methylpropylsulphinyl; 1 , 1 -dimethylethylsulphinyl; pentylsulphinyl ; 1 -methylbutylsu!phinyl ; 2-methylbutylsulphinyl; 3-methylbutylsulphinyl ; 2,2- dimethyl propylsulphinyl; l -ethylpropylsulphinyl; hexylsulphinyl; 1 , 1 -dimethyIpropyIsulphinyl
  • arylsulfinyl i ncludes Ar-S(O), wherein Ar can be any carbocyle or heterocyicle. This definition also applies to alkylsulfinyl as a part of a composite substituent, for example haloalkylsulfinyl etc., unless specifically defined elsewhere.
  • alkyl sulfonyl means alkyl substitution on sulfonyl group. Non-limiting examples of "alkylsulfonyl” include methylsulphonyl; ethylsulphonyl; propylsulphony!
  • alkylamino dialkylamino
  • l ike l ike
  • Carbocycle or carbocyclic includes “aromatic carbocyclic ring system” and “nonaromatic carbocylic ring system” or polycyclic or bicyclic (spiro, fused, bridged, nonfused) ring compounds in which ring may be aromatic or non-aromatic (where aromatic indicates that the Hueckel rule is satisfied and non-aromatic indicates that the Hueckel rule is not statisfied).
  • hetero in connection with rings refers to a ring in which at least one ring atom is not carbon and which can contain heteroatoms independently selected from the group comprising of nitrogen, oxygen, sulfur, etc.
  • hetero in connection with atom refer to an atom independently selected from nitrogen, sulfur, oxygen, etc.
  • non-aromatic heterocyle includes fused or unfused three- to fifteen-membered, preferably three- to tweleve-membered, saturated or fully or partially unsaturated heterocycle, monocyclic or polycyclic (spiro, fused, bridged, nonfused) heterocycle wherein heteroatom is selected from the group of oxygen, nitrogen and sulphur; and if the ring contains more than one oxygen atom, they are not directly adjacent;
  • Non-limiting examples of non-aromatic heterocyle include oxetanyl, oxiranyl; aziridinyl; thi iranyl, azetidinyl, thiethanyl, dithiethanyl, diazetidinyl, 2-tetrahydrofuranyl; 3-tetrahydrofuranyl; 2- tetrahydrothienyl; 3-tetrahydrothienyl; 2-pyrrolidinyl; 3-pyrrolidinyl; 3-is
  • aromatic heterocycle or heteroaryi includes fused or unfused three to fifteen membered, preferably three to tweleve membered, more preferably 5 or 6 membered; monocyclic or polycyclic unsaturated ring system, containing heteroatoms selected from the group of oxygen, nitrogen, sulphur, etc.
  • Non-limiting examples of 5 membered heteroaryi groups include fury], thienyl, pyrrolyl, isoxazo!yl, isothiazolyl, pyrazolyl, oxazolyl, thiazolyl, imidazolyl, 1,2,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4-triazolyl, 1,3,4-oxadiazolyl, 1,3,4-thiadiazolyl, 1,3,4-triazolyl, tetrazolyl; nitrogen-boiided 5-membered heteroaryi containing one to four nitrogen atoms, or benzofused nitrogen-bonded 5-membered heteroaryi containing one to three nitrogen atoms: 5-membered heteroaryi groups which, in addition to carbon atoms, may contain one to four nitrogen atoms or one to three nitrogen atoms as ring members and in which two adjacent carbon ring members or one nitrogen and one adjacent carbon ring member may be bridged by a buta-
  • Non-limiting examples of 6 membered heteroaryi groups include 2-pyridinyl; 3-pyridinyl; 4-pyridinyl; 3- pyridazinyl; 4-pyridazinyl; 2-pyrimidinyl; 4-pyrimidinyl; 5-pyrimidinyl; 2-pyrazinyl; l,3,5-triazin-2-yl; l,2,4-triazin-3-yl; l,2,4,5-tetrazin-3-yl and the like.
  • Non-limiting examples of benzofused 5-membered heteroaryi include indol-l-yl ; indol-2-yl; indol-3-yl; indol-4-yl; indol-5-yl; indol-6-yl; indol-7-yl; benzimidazol-l-yl; benzimidazol-2-yl ; benzimidazol-4-yl; benzimidazol-5-yl; indazol-l-yl; indazol-3-yl; indazol-4-yl; indazol-5-yl ; indazol-6-yl ; indazol-7-yl; indazol-2-yl; l-benzofuran-2-yl; l-benzofuran-3-yl; l-benzofuran-4-yl; l-benzofuran-5-yl; 1 -benzofuran- 6- yl
  • Non-limiting examples of benzofused 6-membered heteroaryi include quinol in-2-yl; quinolin-3-yl; quinolin-4-yl; quinolin-5-yl; quinolin-6-yl; quinolin-7-yl ; quinolin-8-yl; isoquinolin-l-yl; isoquinolin-3-yl; isoquinolin-4-yl ; isoquinolin-5-yl ; isoquinolin-6-yl; isoquinolin-7-yl ; isoquinolin-8-yl and the like.
  • This definition also applies to heteroaryl as a part of a composite substituent, for example heteroarylalkyl etc., unless specifically defined elsewhere.
  • alkylsilyl means branched and/or straight-chain alkyl radicals attached to a silicon atom.
  • alkylsilyl include trimefhylsilyl, triethylsilyl, t-butyl-dimethylsilyl and the like or different isomers.
  • haloalkylsilyl means at least one alkyl radicals of alkylsilyl is partially or fully substituted with halogen atoms which may be the same or different.
  • alkoxyalkylsilyl denotes at least one alkyl radical of alkylsilyl is substituted with one or more alkoxy radicals which may be the same or different.
  • alkylsilyloxy denotes an alkylsilyl moiety attached through oxygen.
  • alkyl carbonyl means alkyl group substituted on the carbonyl group. Non-limiting examples of “alkylcarbonyl” include C(0)CH 3 , C(0)CH 2 CH 2 CH 3 and C(0)CH(CH 3 ) 2 .
  • alkoxycarbonyl means alkoxy group substituted on the carbonyl group.
  • alkylaminocarbonyl means alkylamino substituted on the carbonyl group.
  • dialkylaminocarbonyl means dialkylam ino substituted on the carbonyl group.
  • haloalkylsufonylaminocarbonyl alkylsulfonylaminocarbonyl
  • alkyithioalkoxycarbonyl alkoxycarbonylalkylamino
  • the total number of carbon atoms in a substituent group is indicated by the "Q to C " prefix wherein i and j are numbers from 1 to 21.
  • C r C 3 alky!sulfonyl designates methylsulfonyl through propylsulfonyl
  • C 2 alkoxyalkyl designates CH 3 OCH 2
  • C 3 alkoxyalkyl designates, for example, CH 3 CH(OCH 3 ), CH 3 OCH 2 CH 2 or CH 3 CH 2 OCH 2
  • C 4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH 3 CFI 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • all substituents are attached to these rings through any avai lable carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
  • the substituents may be optional ly further substituted.
  • any deviation from such numerical values shall stil l fall within the scope of the present invention if that deviation fol lows the same scientific principle as that of the present invention.
  • the term "pest” for the purpose of the present invention includes but is not limited to fungi, stramenopiles (oomycetes), bacteria, nematodes, mites, ticks, insects and rodents.
  • the term "plant” is understood here to mean al l plants and plant populations, such as desired and undesired wi ld plants or crop plants (including naturally occurring crop plants). Crop plants may be plants which can be obtained by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or combinations of these methods, including the transgenic plants and including the plant cultivars which are protectable and non-protectable by plant breeders' rights.
  • plant includes a living organism of the kind exemplified by trees, shrubs, herbs, grasses, ferns, and mosses, typically growing in a site, absorbing water and required substances through its roots, and synthesizing nutrients in its leaves by photosynthesis.
  • plant for the purpose of the present invention include but are not limited to agricultural crops such as wheat, rye, barley, triticale, oats or rice; beet, e.g. sugar beet or fodder beet; fruits, such as pomes, stone fruits or soft fruits, e.g.
  • the plant for the purpose of the present invention include but is not limited to cereals, corn, rice, soybean and other leguminous plants, fruits and fruit trees, grapes, nuts and nut trees, citrus and citrus trees, any horticultural plants, cucurbitaceae, oleaginous plants, tobacco, coffee, tea, cacao, sugar beet, sugar cane, cotton, potato, tomato, onions, peppers and vegetables, ornamentals, any floricultural plants and other plants for use of human and animals.
  • plant parts is understood to mean all parts and organs of plants above and below the ground.
  • plant parts includes but is not limited to cuttings, leaves, twigs, tubers, flowers, seeds, branches, roots including taproots, lateral roots, root hairs, root apex, root cap, rhizomes, slips, shoots, fruits, fruit bodies, bark, stem, buds, auxil obviouslyy buds, meristems, nodes and internodes.
  • locus thereof includes soil, surroundings of plant or plant parts and equipment or tools used before, during or after sowing/planting a plant or a plant part.
  • Appl ication of a compound or compounds of the present invention or the compound of the present invention in a composition optionally comprising at-least one other active compatible compound to a plant or a plant material or locus thereof include application by a technique known to a person skilled in the art which include but is not limited to spraying, coating, dipping, fumigating, impregnating, injecting and dusting.
  • adhered means adhered to a plant or plant part either physically or chemically.
  • the present invention relates to a compound selected from Formula I,
  • the present invention is inclusive of salts, metal complexes, N-oxides, isomers, and polymorphs of compound of Formula I, wherein
  • E is a fragment selected from the group consisting of E- 1 to E-5:
  • E is E-1 .
  • T 1 , T 2 T “ ' and T 4 are independently selected from 5- or 6- membered aryl ring or 5- or 6-membered saturated or partially saturated cyclic ring or 5- or 6- membered heteroaryl ring or 5- or 6-membered saturated or partially saturated heterocyclic ring, wherein each ring member of heteroaryl ring is selected from C, N, O and S, and wherein each ring member of heterocyclic ring is selected from C, N, O, S(0).
  • T 1 , T 2 , T 3 and T 4 are optionally substituted by one or more R 1 on C atoms and one or more R 2 on hetero atoms.
  • T 1 Non-limiting representative examples of T 1 are depicted herein below.
  • T 2 ? T 3 and T 4 are independently selected from C r C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C r C 6 haloalkyl, C 2 -Q, haloalkenyl, C 2 -C 6 haloalkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 halocycloalkyl, C r C 6 alkyl C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl C r C 6 alkyl, C 3 -C 8 cycloalkyl C 3 -C 8 cycloalkyl, C 3 -C 8 halocycloalkyl C
  • A is C(R 4 ) 2 or NR 5 .
  • Z is C or N. In one of the preferred embodiments Z is C.
  • the substitutent R 3 is selected from hydrogen, halogen, cyano, hydroxy, amino, aldehyde, carboxylic acid, C r C 6 alkyl, C 2 -C 5 alkenyl, C 2 -C 6 alkynyl, C ,-C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyi, C C 6 alkyl C -C 6 cycloalkyl, C : ,-C 6 cycloalkyl C C 6 alkyl, C 3 -C 6 halocycloalkyi C
  • R 3 is selected from hydrogen, C r C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C r C 4 haloalkyl, C,-C 4 alkoxy, halogen, cyano and hydroxy.
  • G is selected from optionally substituted G l to G63, each substituent selected from R 3a on carbon ring members and R l la on nitrogen ring members.
  • G l to G63 are as depicted herein below:
  • R 3a and R l la may be attached to one or more possible position/s.
  • the substituent R 3a is hydrogen or R 3b .
  • the substituent R 3b is a phenyl or 5- or 6-membered heteroaryl ring optionally substituted with one or more substituents independently selected from R 4a on carbon ring members and R b on nitrogen ring members.
  • R 31 ' is independently C C 3 alkyl, C r C 3 haloalkyi or halogen.
  • the substituent R' ,a is independently selected from C r C 6 alkyl, C 2 -Q, alkenyl, C 2 -C 6 alkynyl, C 3 - C 6 cycloalkyl, C 3 -C 6 cycloalkyl C r C 6 alkyl, C r C 6 alkyl C 3 -C 6 cycloalkyl, C ,-C 6 haloalkyi C 3 -C 6 cycloalkyl, C r C 6 haloalkyi, C 2 -C 6 haloaikenyl, C 2 -C 6 haloalkynyl, C 3 -C 6 halocycloalkyl, halogen, hydroxy, amino, cyano, nitro, C r C 6 alkoxy, C r C 6 haloalkoxy, C r C 6 alkylthio, C r C 6 alkylsulfinyl, C r C 6 alkylsul
  • the substituent R 4b is independently selected from C r C b alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 - C 6 cycloalkyl, Ci-C 6 haloalkyi, C 2 -C 6 haloaikenyl, C 2 -C 6 haloalkynyl, C 3 -C 6 halocycloalkyl and Cj-C 6 alkoxy C C 6 alkyl.
  • the substituent R l i a is hydrogen or R l lb and the substituent R i l b is independently C C 3 alkyl, C 2 - C c alkenyl, C 2 -C alkynyl, C 3 -C 6 cycloalkyl, C C 6 haloalkyi, C 2 -C 6 haloaikenyl, C 2 -C 6 haloalkynyl, C 3 - C 6 halocycloalkyl and C r C 6 alkoxy C
  • J is selected from fragments of Formula II & III
  • L 6 and L 7 together with the atoms to which they are attached may form a 4- to 7- membered carbocycl ic or heterocycl ic ring or ring system.
  • the substituent R n together with L 6 or L 7 or G or Q or R 12 or R 13 or R 14 or R 15 may form a 4- to 7- membered carbocyclic or heterocyclic ring or ring system.
  • m is an integer 0 to 1 ;
  • Q is independently phenyl, benzyl, naphthalenyl, a 5- or 6- membered aryl ring, an 8- to 1 1 - membered aryl multi-cyclic ring system, an 8- to 1 1 - membered aryl fused ring system, a 5- or 6- membered heteroaryl ring, an 8- to 1 1 - membered heteroaryl multi-cyclic ring system or an 8- to 1 1 - membered heteroaryl fused ring system, each ring member of the ring or the ring system is selected from C, N, O and S, and each ring or ring system is optionally substituted with R 14 on carbon atoms and R 15 on hetero atoms.
  • Q is selected from Q l to Q99 and the presentation " " is a single or a double bond.
  • the substituent R 14 may be attached to one or more position/s. ⁇
  • R 1 , R 2 , R 6 , R 7 , R 8 , R 9 , R i0 , R 14 , R 15 , R 18 , R 19 , R 20 , R 2 ', R 2 " and R 27 are independently selected from hydrogen, halogen, hydroxy, cyano, nitro, C r C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C C 6 haloalkyl, C 2 -C ⁇ , haioalkenyl, C 2 -C 6 haloa!kynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 halocycloaikyl, Ci-C 6 alkyl C 3 -C 8 cycloalkyl, C -C 8 cycloalkyl C r C 6 alkyl, C 3 -C 8 cycloalkyl C 3 -C 8 cycloalkyl, C 3 -C 8
  • R 16 and R 17 are independently selected from C r C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 3 -C 6 cycloalkyl C C 6 alkyl, C r C 6 alkyl C 3 -C 6 cycloalkyl, C,-C 6 haloalkyl C 3 -C 6 cycloalkyl, C r C 6 haloalkyl, C r C 6 alkoxy and C r C 6 haloalkoxy.
  • W is O or S. Preferably W is O.
  • L 1 is a direct bond or O or S or NR 23 .
  • R 4 , R 12 , and R 22 are independently selected from hydrogen, halogen, cyano, hydroxy, aldehyde, C,-C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C,-C 6 haloalkyl, C -C 6 haloalkenyl, C 2 - C 6 haloalkynyl, C r C 6 alkoxy C r C 6 alkyl, C r C 6 alkylthio C r C 6 alkyl, C r C 6 alkylsulfinyl C C 6 alkyl, C,- C alkylsulfonyl C -C b alkyl, C r C 6 alkylcarbonyl, C r C 6 haloalkylcarbonyl, C
  • R 5 , R 13 , and R 23 are independently selected from hydrogen, C r C6 alkyl, C?-C ( , alkenyl, C 2 -C 6 alkynyl, C r C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C r C 6 alkoxy C
  • the presentation " " in ring D is a single bond when Z is N. Further, the presentation “ “ “ in ring D is a single or double bond when Z is C. In one of the preferred embodiment, the presentation " " is a single bond.
  • n is an integer ranging from 0 to 9 with a proviso that when Z is N, "n” is an integer ranging from 0 to
  • a is independently 0, 1 or 2.
  • the novel and inventive compounds of the present invention, the salts, isomers, metal complexes, N- oxides and polymorphs thereof are effective in preventing against and controlling phytopathogenic microorganisms.
  • An anion part of the salt in case the compound of Formula I is cationic or capable of forming a cation can be inorganic or organic.
  • a cation part of the salt in case the compound of Formula I is anionic or capable of forming an anion can be inorganic or organic.
  • inorganic anion part of the salt examples include but are not limited to chloride, bromide, iodide, fluoride, sulphate, phosphate, nitrate, nitrite, hydrogen carbonates and hydrogen sulphate.
  • organic anion part of the salt examples include but are not l imited to formate, alkanoates, carbonates, acetates, trifluoroacetate, trichloroacetate, propionate, glycolate, thiocyanate, lactate, succinate, malate, citrates, benzoates, cinnamates, oxalates, alkylsulphates, alkylsulphonates, arylsulphonates aryldisulphonates, alkylphosphonates, arylphosphonates, aryldiphosphonates, p-toluenesulphonate, and salicylate. ;
  • Examples of inorganic cation part of the salt include but are not limited to alkal i and alkaline earth metals.
  • Examples of organic cation part of the salt include but are not limited to pyridine, methyl amine, imidazole, benzimidazole, histidine, phosphazene, tetramethyl ammonium, tetrabutyl ammonium, choline and trimethyl amine.
  • Metal ions in metal complexes of the compound of Formula I are especially the ions of the elements of the second main group, especially calcium and magnesium, of the third and fourth main group, especially aluminium, tin and lead, and also of the first to eighth transition groups, especially chromium, manganese, iron, cobalt, nickel, copper, zinc and others. Particular preference is given to the metal ions of the elements of the fourth period and the first to eighth transition groups.
  • the metals can be present in the various valencies that they can assume.
  • Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts.
  • Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types).
  • polymorph refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice.
  • polymorphs can have the same chemical composition, they can also differ in composition due the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability.
  • beneficial effects e.g., suitability for preparation of useful formulations, improved biological performance
  • the present invention further relates to a process for preparing the compound of Formula I.
  • the process comprises a step of reacting JQ- 1 with a compound of Formula 5 to obtain a compound of Formula 4.
  • the compound of Formula 4 upon deprotecting provides a compound of Formula 2 which is reacted with E- 1 A to obtain the compound of Formula I;
  • W is O or S; R", G, Q and T 1 are as defined herein above.
  • W is O or S; R 1 1 , G, Q and T 1 are as defined herein above.
  • the present invention also relates to the following intermediates 4 and 2 which are useful in the synthesis of the compound of Formula 1 : wherein, R " , G, L 6 , and Q are as defined herein above.
  • the present invention also relates a composition comprising the compound of Formula 1 and one or more excipient.
  • the compound of Formula I of the present invention in the composition can be an agriculturally acceptable salt, metal complex, constitutional isomer, stereo-isomer, diastereoisomer, enantiomer, chiral isomer, atropisomer, conformer, rotamer, tautomer, optical isomer, geometric isomer, polymorph, or N- oxide thereof.
  • the excipient may be an inert carrier or any other essential ingredient such as surfactants, additives, solid diluents and liquid diluents.
  • composition of the present invention may additionally comprise at least one active compatible compound selected from fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilisers and nutrients.
  • active compatible compounds selected from fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilisers and nutrients.
  • the concentration of the compound of Formula I in the composition of the present invention ranges from 1 to 90% by weight with respect to the total weight of the composition, preferably from 5 to 50% by weight with respect to the total weight of the composition.
  • the known and reported active compounds such as fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics and nutrients can be combined with at least one compound of Formula I of the present invention.
  • active compounds such as fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics and nutrients
  • fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilizers and nutrients disclosed and reported in WO201776739 (A to O) can be combined with compound of Formula I of the present invention.
  • the present invention also relates to such combinations comprising the compound of the present invention and active compatible compounds reported in WO201776739.
  • fungicides insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilizers and nutrients reported in WO201776739, are not reproduced herein for the sake of brevity and are incorporated herein by way of reference as non-limiting examples to be combined with at least one compound of Formula I of the present invention.
  • the present invention also relates to a use of the compound of Formula 1 or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I for controlling or preventing phytopathogenic micro-organisms such as fungi, stramenopiles, bacteria, insects, nematodes, trematodes, and mites in agricultural crops and or horticultural crops.
  • the present invention also relates to a use of the compound of Formula I or the combination or the composition for control ling or preventing phytopathogenic micro-organisms in agricultural crops and or horticulture crops.
  • the compound of Formula I or the combination or the composition of the present invention may be used to treat several fungal pathogens.
  • pathogens of fungal diseases which can be treated in accordance with the invention include:
  • Albugo species for example Albugo Candida
  • Bremia species for example Bremia lactucae
  • Peronospora species for example Peronospora pisi or P. brassicae
  • Phytophthora species for example Phytophthora infestans
  • Plasmopara species for example Plasmopara viticola
  • Pseudoperonospora species for example Pseudoperonospora humuli or Pseudoperonospora cubensis
  • Pythium species for example Pythium ultimum
  • Pythium species for example Pythium ultimum
  • Blumeria species for example Blumeria graminis
  • Podosphaera species for example Podosphaera leucotricha
  • Sphaerotheca species for example Sphaerotheca fuliginea
  • Uncinula species for example Uncinula necator
  • Erysiphe species for example Erysiphe cichoracearu
  • Gymnosporangium species for example Gymnosporangium sabinae
  • Hemileia species for example Hemileia vastatrix
  • Phakopsora species for example Phakopsora pachyrhizi or Phakopsora meibomiae
  • Puccinia species for example Puccinia recondita, Puccinia graminis oder Puccinia striiformis
  • Uromyces species for example Uromyces appendiculatus
  • Ear and panicle diseases caused, for example, by Alternaria species, for example Alternaria spp.; Aspergillus species, for example Aspergillus flavus; Cladosporium species, for example Cladosporium cladosporioides; Claviceps species, for example Claviceps purpurea; Fusarium species, for example Fusarium culmorum; Gibberella species, for example Gibberella zeae; Monographella species, for example Monographella nivalis; Stagnospora species, for example Stagnospora nodorum;
  • Sphacelotheca species for example Sphacelotheca reiliana
  • Tilletia species for example Tilletia caries or Tilletia controversa
  • Urocystis species for example Urocystis occulta
  • Ustilago species for example Ustilago nuda
  • Seed- and soil-borne rot and wilt diseases, and also diseases of seedlings caused, for example, by Alternaria species, for example Alternaria brassicicola; Aphanomyces species, for example Aphanomyces euteiches; Ascochyta species, for example Ascochyta lentis; Aspergillus species, for example Aspergillus flavus; Cladosporium species, for example Cladosporium herbarum; Cochliobolus species, for example Cochliobolus sativus (conidial form: Drechs!era, Bipolaris Syn: Helminthosporium); Colletotrichiim species, for example Colletotrichiim coccodes; Fusarium species, for example Fusarium culmorum; Gibberella species, for example Gibberella zeae; Macrophomirta species, for example Macrophomina phaseolina; Microdochium species, for example Microdochium nivale; Monographella species,
  • Botrytis species for example Botrytis cinerea
  • Rhizoctonia species for example Rhizoctonia solani
  • Helminthosporium species for example Helminthosporium solani
  • Xanthomonas species for example Xanthomonas campestris pv. oryzae
  • Pseudomonas species for example Pseudomonas syringae pv.
  • Plants which can be treated in accordance with the invention include the following: Rosaceae sp (for example pome fruits such as apples, pears, apricots, cherries, almonds and peaches), Ribesioidae sp., Juglandaceae sp., Betulaceae sp., Anacardiaceae sp., Fagaceae sp. , Moraceae sp. , Oleaceae sp. , Actinidaceae sp. , Lauraceae sp. , Musaceae sp. (for example banana trees and plantations), Rubiaceae sp. (for example coffee), Theaceae sp.
  • Rosaceae sp for example pome fruits such as apples, pears, apricots, cherries, almonds and peaches
  • Ribesioidae sp. Juglandaceae sp.
  • Sterculiceae sp. for example lemons, oranges and grapefruit
  • Vitaceae sp. for example grapes
  • Solanaceae sp. for example tomatoes, peppers
  • Liliaceae sp. for example lettuce
  • Umbelliferae sp. for example lettuce
  • Umbelliferae sp. for example lettuce
  • Alliaceae sp. for example leek, onion
  • Papilionaceae sp. for example peas
  • major crop plants such as PoaceaelGramineae sp.
  • Asteraceae sp. for example sunflower
  • Brassicaceae sp. for example white cabbage, red cabbage, broccoli, cauliflower, Brussels sprouts, pak choi, kohlrabi, radishes, and oilseed rape, mustard, horseradish and cress
  • Fabacae sp. for example bean, peanuts
  • Papilionaceae sp. for example soya bean
  • Solanaceae sp. for example potatoes), Chenopodiaceae sp.
  • the agricultural or horticulture crops are wheat, rye, barley, triticale, oats or rice; beet, e.g. sugar beet or fodder beet; fruits, such as pomes, stone fruits or soft fruits, e.g.
  • the agriculture or horticulture crops are cereals, corn, rice, soybean and other leguminous plants, fruits and fruit trees, nuts and nut trees, citrus and citrus trees, any horticultural plants, cucurbitaceae, oleaginous plants, tobacco, coffee, tea, cacao, sugar beet, sugar cane, cotton, potato, tomato, onions, peppers, other vegetables and ornamentals.
  • the present invention further relates to the use of the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I for treating seeds with the purpose of protecting the seeds, the germinating plants and emerged seedlings against phytopathogenic micro-organisms.
  • the present invention further relates to seeds which have been treated with the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula 1 for protection from phytopathogenic micro-organisms.
  • the present invention also relates to a method of controlling or preventing infestation of useful plants by phytopathogenic micro-organisms in agricultural crops and or horticultural crops wherein the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I, is applied to the plants, to parts thereof or the locus thereof.
  • the effective amount of compound of Formula I ranges from 1 to 5000 gai per hectare.
  • the present invention relates to the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I applied to a plant, plant parts or locus thereof.
  • the present invention furthermore includes a method for treating seed, particularly seeds (dormant, primed, pregerminated or even with emerged roots and leaves) treated with the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula 1.
  • seed particularly seeds (dormant, primed, pregerminated or even with emerged roots and leaves) treated with the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula 1.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I is applied to the seeds of plants for controll ing or preventing infestation of useful plants by phytopathogenic micro-organisms in agricultural and or horticultural corps.
  • methods for the treatment of seed should also take into consideration the intrinsic phenotypes of transgenic plants in order to achieve optimum protection of the seed and the germinating plant with a minimum of crop protection compositions being employed.
  • One of the advantages of the present invention is that the treatment of the seeds with the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I not only protects the seed itself, but also the resulting plants after emergence, from animal pests and/or phytopathogenic harmful micro-organisms. In this way, the immediate treatment of the crop at the time of sowing or shortly thereafter protect plants as well as seed treatment in prior to sowing. It is likewise considered to be advantageous that the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula 1 can be used especially also for transgenic seed, in which case the plant which grows from this seed is capable of expressing a protein which acts against pests, herbicidal damage or abiotic stress.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I is suitable for protection of seed of any plant variety which is used in agriculture, in the greenhouse, in forests or in horticulture. More particularly, the seed is that of cereals (such as wheat, barley, rye, millet and oats), oilseed rape, maize, cotton, soybeen, rice, potatoes, sunflower, beans, coffee, beet (e.g. sugar beet and fodder beet), peanut, vegetables (such as tomato, cucumber, onions and lettuce), lawns and ornamental plants. Of particular significance is the treatment of the seed of wheat, soybean, oilseed rape, maize and rice.
  • cereals such as wheat, barley, rye, millet and oats
  • oilseed rape e.g. sugar beet and fodder beet
  • peanut e.g. sugar beet and fodder beet
  • vegetables such as tomato, cucumber, onions and lettuce
  • transgenic seed with the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I, is of particular significance.
  • heterologous genes in transgenic seeds may originate, for example, from microorganisms of the species of Bacillus, Rhizobium, Pseudomonas, Serratia, Trichoderma, Clavibacter, Glomus or Gliocladium.
  • These heterologous genes preferably originate from Bacillus sp., in which case the gene product is effective against the European corn borer and/or the Western corn rootworm.
  • the heterologous genes originate from Bacillus thuringiensis.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I is applied to seeds.
  • the seed is treated in a state in which it is sufficiently stable for no damage to occur in the course of treatment.
  • seeds can be treated at any time between harvest and some time after sowing. It is customary to use seed which has been separated from the plant and freed from cobs, shells, stalks, coats, hairs or the flesh of the fruits. For example, it is possible to use seed which has been harvested, cleaned and dried down to a moisture content of less than 15% by weight.
  • seed which, after drying, for example, has been treated with water and then dried again or seeds just after priming, or seeds stored in primed conditions or pre-germinated seeds, or seeds sown on nursery trays, tapes or paper.
  • the amount of the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I appl ied to the seed and/or the amount of further additives is selected such that the germination of the seed is not impaired, or that the resulting plant is not damaged.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can be applied directly, i.e. without containing any other components and without having been diluted. In general, it is preferable to apply the compositions comprising compounds of Formula I to the seed in the form of a suitable formulation. Suitable formulations and methods for seed treatment are known to those skilled in the art.
  • the compound of Formula I can be converted to the customary formulations relevant to on-seed applications, such as solutions, emulsions, suspensions, powders, foams, slurries or combined with other coating compositions for seed, such as film forming materials, pelleting materials, fine iron or other metal powders, granules, coating material for inactivated seeds, and also ULV Formulations.
  • seeds can be coated with polymer.
  • the polymer coating is comprised of a binder, a wax and a pigment, and one or more stabilizers in an amount effective to stabilize the suspension.
  • the binder can be a polymer selected from the group comprising of vinyl acetate-ethylene copolymer, vinyl acetate homopolymer, vinyl acetate-acrylic copolymer, vinylacryl ic, acrylic, ethylene-vinyl chloride, vinyl ether maleic anhydride, or butadiene styrene. Other simi lar polymers can be used.
  • formulations are prepared in a known manner, by mixing the active ingredients or active ingredient combinations with customary additives, for example customary extenders and solvents or di luents, dyes, wetting agents, dispersants, emulsifiers, antifoams, preservatives, secondary thickeners, adhesives, gibberel lins, and also water.
  • customary additives for example customary extenders and solvents or di luents, dyes, wetting agents, dispersants, emulsifiers, antifoams, preservatives, secondary thickeners, adhesives, gibberel lins, and also water.
  • Useful dyes which may be present in the seed dressing Formulations usable in accordance with the invention are all dyes which are customary for such purposes. It is possible to use either pigments, which are sparingly soluble in water, or dyes, which are soluble in water. Examples include the dyes known by the names Rhodamine B, C.I. Pigment Red 1 12 and C.I. Solvent Red 1 .
  • Useful wetting agents which may be present in the seed dressing formulations usable in accordance with the invention are all substances which promote wetting and which are conventionally used for the formulation of active agrochemical ingredients.
  • Usable with preference are alkylnaphthalenesulphonates, such as diisopropyl- or diisobutylnaphthalenesulphonates.
  • Useful dispersants and/or emulsifiers which may be present in the seed dressing formulations usable in accordance with the invention are all nonionic, anionic and cationic dispersants conventionally used for the formulation of active agrochemical ingredients. Usable with preference are nonionic or anionic dispersants or mixtures of nonionic or anionic dispersants.
  • Useful nonionic dispersants include especially ethylene oxide/propylene oxide block polymers, alkylphenol polyglycol ethers and tristryrylphenol polyglycol ether, and the phosphated or sulphated derivatives thereof.
  • Suitable anionic dispersants are especially lignosulphonates, polyacrylic acid salts and arylsulphonate/formaldehyde condensates.
  • Antifoams which may be present in the seed dressing formulations usable in accordance with the invention are all foam-inhibiting substances conventionally used for the formulation of active agrochemical ingredients. Silicone antifoams and magnesium stearate can be used with preference.
  • Preservatives which may be present in the seed dressing formulations usable in accordance with the invention are all substances usable for such purposes in agrochemical compositions. Examples include dichlorophene and benzyl alcohol hemi formal.
  • Secondary thickeners which may be present in the seed dressing formulations usable in accordance with the invention are all substances usable for such purposes in agrochemical compositions.
  • Preferred examples include cellulose derivatives, acrylic acid derivatives, xanthan, modified clays and finely divided silica.
  • Adhesives which may be present in the seed dressing formulations usable in accordance with the invention are all customary binders usable in seed dressing products. Preferred examples include polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol and tylose.
  • the formulations for on-seed applications usable in accordance with the invention can be used to treat a wide variety of different kinds of seed either directly or after prior dilution with water.
  • the concentrates or the preparations obtainable therefrom by dilution with water can be used to dress the seed of cereals, such as wheat, barley, rye, oats, and triticaie, and also seeds of maize, soybean, rice, oilseed rape, peas, beans, cotton, sunflowers, and beets, or else a wide variety of different vegetable seeds.
  • the formulations usable in accordance with the invention, or the dilute preparations thereof, can also be used for seeds of transgenic plants. In this case, enhanced effects may also occur in interaction with the substances formed by expression.
  • all mixing units usable customarily for on-seed applications are useful. Specifically, the procedure in on-seed applications is to place the seeds into a mixer, to add the particular desired amount of the formulations, either as such or after prior dilution with water, and to mix everything until all applied formulations are distributed homogeneously on the seeds. If appropriate, this is followed by a drying operation.
  • the application rate of the formulations usable in accordance with the invention can be varied within a relatively wide range. It is guided by the particular content of the active ingredients in the formulations and by the seeds.
  • the application rates of each single active ingredient are generally between 0.001 and 1 5 gai per kilogram of seed, preferably between 0.01 and 5 gai per kilogram of seed.
  • the application rate of the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I is: in the case of treatment of plant parts, for example leaves: from 0. 1 to 10000 gai/ha, preferably from 5 to 1000 gai/ha, more preferably from 5 to 100 gai/ha (in the case of application by watering or dripping, it is even possible to reduce the application rate, especial ly when inert substrates such as rockwool or perlite are used); in the case of seed treatment: from 0.
  • the compound of Formula I may, at particular concentrations or appl ication rates, also be used as safeners, growth regulators or agents to improve plant properties, or as microbicides, for example as fungicides, antimycotics, bactericides, viricides (including compositions against viroids) or as compositions against phytoplasmas MLO (Mycoplasma-like organisms) and RLO (Rickettsia-like organisms).
  • the compound of Formula I may intervene in physiological processes of plants and can therefore also be used as plant growth regulators.
  • Plant growth regulators may exert various effects on plants. The effect of the substances depends essentially on the time of application in relation to the developmental stage of the plant, the plant variety and also on the amounts of active ingredient applied to the plants or their environment and on the type of application. In each case, growth regulators should have a particular desired effect on the crop plants.
  • Growth regulating effects comprise earlier germination, better emergence, more developed root system and/or improved root growth, increased ability of tillering, more productive tillers, earlier flowering, increased plant height and/or biomass, shorting of stems, improvements in shoot growth, number of kernels/ear, number of ears/m 2 , number of stolons and/or number of flowers, enhanced harvest index, bigger leaves, less dead basal leaves, improved phyllotaxy, earlier maturation/ earlier fruit finish, homogenous riping, increased duration of grain filling, better fruit finish, bigger fruit/vegetable size, sprouting resistance and reduced lodging.
  • Increased or improved yield is referring to total biomass per hectare, yield per hectare, kernel/fruit weight, seed size and/or hectolitre weight as well as to improved product quality, comprising: improved processabil ity relating to size distribution (kernel, fruit, etc.), homogenous riping, grain moisture, better milling, better vinification, better brewing, increased juice yield, harvestability, digestibility, sedimentation value, falling number, pod stability, storage stability, improved fiber length/strength/uniformity, increase of milk and/or meet quality of silage fed animals, adaption to cooking and frying; further comprising improved marketability relating to improved fruit/grain quality, size distribution (kernel, fruit, etc.), increased storage/shelf-life, firmness /softness, taste (aroma, texture, etc.), grade (size, shape, number of berries, etc.), number of berries/fruits per bunch, crispness, freshness, coverage with wax, frequency of physiological disorders, colour, etc.; further comprising increased desired ingredients
  • protein content protein content, fatty acids, oil content, oil quality, aminoacid composition, sugar content, acid content (pH), sugar/acid ratio (Brix), polyphenols, starch content, nutritional quality, gluten content/index, energy content, taste, etc.; and further comprising decreased undesired ingredients such as e.g. less mycotoxines, less aflatoxines, geosmin level, phenolic aromas, lacchase, polyphenol oxidases and peroxidases, nitrate content etc.
  • decreased undesired ingredients such as e.g. less mycotoxines, less aflatoxines, geosmin level, phenolic aromas, lacchase, polyphenol oxidases and peroxidases, nitrate content etc.
  • Plant growth-regulating compounds can be used, for example, to slow down the vegetative growth of the plants.
  • Such growth depression is of economic interest, for example, in the case of grasses, since it is thus possible to reduce the frequency of grass cutting in ornamental gardens, parks and sport facilities, on roadsides, at airports or in fruit crops.
  • Also of significance is the inhibition of the growth of herbaceous and woody plants on roadsides and in the vicinity of pipelines or overhead cables, or quite generally in areas where vigorous plant growth is unwanted.
  • growth regulators for inhibition of the longitudinal growth of cereal. This reduces or completely eliminates the risk of lodging of the plants prior to harvest.
  • growth regulators in the case of cereals can strengthen the culm, which also counteracts lodging.
  • the employment of growth regulators for shortening and strengthening culms allows the deployment of higher fertilizer volumes to increase the yield, without any risk of lodging of the cereal crop.
  • vegetative growth depression allows denser planting, and it is thus possible to achieve higher yields based on the soil surface.
  • Another advantage of the smaller plants obtained in this way is that the crop is easier to cultivate and harvest. Reduction of the vegetative plant growth may also lead to increased or improved yields because the nutrients and assimilates are of more benefit to flower and fruit formation than to the vegetative parts of the plants.
  • growth regulators can also be used to promote vegetative growth. This is of great benefit when harvesting the, vegetative plant parts. However, promoting vegetative growth may also promote generative growth in that more assimilates are formed, resulting in more or larger fruits.
  • beneficial effects on growth or yield can be achieved through improved nutrient use efficiency, especial ly nitrogen (N)-use efficiency, phosphours (P)-use efficiency, water use efficiency, improved transpiration, respiration and/or C0 2 assimilation rate, better nodulation, improved Ca- metabolism etc.
  • growth regulators can be used to alter the composition of the plants, which in turn may result in an improvement in qual ity of the harvested products. Under the influence of growth regulators, parthenocarpic fruits may be formed. In addition, it is possible to influence the sex of the flowers. It is also possible to produce sterile pollen, which is of great importance in the breeding and production of hybrid seed.
  • growth regulators can control the branching of the plants.
  • by breaking apical dominance it is possible to promote the development of side shoots, which may be highly desirable particularly in the cultivation of ornamental plants, also in combination with an inhibition of growth.
  • side shoots which may be highly desirable particularly in the cultivation of ornamental plants, also in combination with an inhibition of growth.
  • the amount of leaves on the plants can be controlled such that defoliation of the plants is achieved at a desired time.
  • defoliation plays a major role in the mechanical harvesting of cotton, but is also of interest for facilitating harvesting in other crops, for example in viticulture.
  • Defoliation of the plants can also be undertaken to lower the transpiration of the plants before they are transplanted.
  • growth regulators can modulate plant senescence, which may result in prolonged green leaf area duration, a longer grain filling phase, improved yield quality, etc.
  • Growth regulators can likewise be used to regulate fruit dehiscence. On the one hand, it is possible to prevent premature fruit dehiscence. On the other hand, it is also possible to promote fruit dehiscence or even flower abortion to achieve a desired mass ("thinning"). In addition, it is possible to use growth regulators at the time of harvest to reduce the forces required to detach the fruits, in order to allow mechanical harvesting or to facilitate manual harvesting.
  • Growth regulators can also be used to achieve faster or else delayed ripening of the harvested material before or after harvest. This is particularly advantageous as it allows optimal adjustment to the requirements of the market. Moreover, growth regulators in some cases can improve the fruit colour. In addition, growth regulators can also be used to synchronize maturation within a certain period of time. This establishes the prerequisites for complete mechanical or manual harvesting in a single operation, for example in the case of tobacco, tomatoes or coffee.
  • growth regulators By using growth regulators, it is additionally possible to influence the resting of seed or buds of the plants, such that plants such as pineapple or ornamental plants in nurseries, for example, germinate, sprout or flower at a time when they are normally not inclined to do so. In areas where there is a risk of frost, it may be desirable to delay budding or germination of seeds with the aid of growth regulators, in order to avoid damage resulting from late frosts.
  • growth regulators can induce resistance of the plants to frost, drought or high salinity of the soil. This allows the cultivation of plants in regions which are normally unsuitable for this purpose.
  • the compound of Formula I or the combination comprising the compound of Formula 1 or the composition comprising the compound of Formula I also exhibit potent strengthening effect in plants. Accordingly, they can be used for mobilizing the defences of the plant against attack by undesirable micro-organisms.
  • Plant-strengthening (resistance-inducing) substances in the present context are substances capable of stimulating the defence system of plants in such a way that the treated plants, when subsequently inoculated with undesirable micro-organisms, develop a high degree of resistance to these microorganisms.
  • plant physiology effects comprise the following:
  • Abiotic stress tolerance comprising tolerance to high or low temperatures, drought tolerance and recovery after drought stress, water use efficiency (correlating to reduced water consumption), flood tolerance, ozone stress and UV tolerance, tolerance towards chemicals like heavy metals, salts, pesticides etc.
  • Biotic stress tolerance comprising increased fungal resistance and increased resistance against nematodes, viruses and bacteria.
  • biotic stress tolerance preferably comprises increased fungal resistance and increased resistance against nematodes.
  • Increased plant vigor comprising plant health / plant quality and seed vigor, reduced stand failure, improved appearance, increased recovery after periods of stress, improved pigmentation (e.g. chlorophyl l content, stay-green effects, etc.) and improved photosynthetic efficiency.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can reduce the mycotoxin content in the harvested material and the foods and feeds prepared therefrom.
  • Mycotoxins include particularly, but not exclusively, the fol lowing: deoxynivalenol (DON), nivalenol, 15-Ac-DON, 3-Ac-DON, T2- and HT2- toxin, fumonisins, zearalenon, moniliformin, fusarin, diaceotoxyscirpenol (DAS), beauve icin, enniatin, fusaroproliferin, fusarenol, ochratoxins, patulin, ergot alkaloids and afiatoxins which can be produced, for example, by the following fungi : Fiisarhim spec, such as F.
  • verticillioides etc. and also by Aspergillus spec, such as A. flaviis, A. parasiticus, A. nomius, A. ochraceus, A. clavatus, A. terreus, A. versicolor, Penicillium spec, such as P. verrucosum, P. viridicatum, P. citrinum, P. expansion, P. claviforme, P. roqueforti, Claviceps spec, such as C. purpurea, C. fusiformis, C. paspali, C. africana, Stachybotrys spec, and others.
  • Aspergillus spec such as A. flaviis, A. parasiticus, A. nomius, A. ochraceus, A. clavatus, A. terreus, A. versicolor, Penicillium spec, such as P. verrucosum, P. viridicatum, P. citrinum, P
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can also be used in the protection of materials, for protection of industrial materials against attack and destruction by phytopathogenic micro-organisms.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can be used as antifouling compositions, alone or in combinations with other active ingredients.
  • Industrial materials in the present context are understood to mean inanimate materials which have been prepared for use in industry.
  • industrial materials which are to be protected by inventive compositions from microbial alteration or destruction may be adhesives, glues, paper, wallpaper and board/cardboard, textiles, carpets, leather, wood, fibers and tissues, paints and plastic articles, cooling lubricants and other materials which can be infected with or destroyed by micro-organisms.
  • Parts of production plants and buildings, for example cooling-water circuits, cooling and heating systems and ventilation and air- conditioning units, which may be impaired by the proliferation of micro-organisms may also be mentioned within the scope of the materials to be protected.
  • Industrial materials within the scope of the present invention preferably include adhesives, sizes, paper and card, leather, wood, paints, cooling lubricants and heat transfer fluids, more preferably wood.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I may prevent adverse effects, such as rotting, decay.; discoloration, decoloration or formation of mould.
  • the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound may also be used against fungal diseases liable to grow on or inside timber.
  • the term "timber" means al l types of species of wood, and all types of working of this wood intended for construction, for example solid wood, high-density wood, laminated wood, and plywood.
  • the method for treating timber according to the invention mainly consists in contacting a composition according to the invention; this includes for example direct application, spraying, dipping, injection or any other suitable means.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can be used to protect objects which come into contact with saltwater or brackish water, especially hulls, screens, nets, buildings, moorings and signalling systems, from fouling.
  • the compound of Formula 1 or the combination comprising the compound of Formula I or the composition comprising the compound of Formula 1 can also be employed for protecting storage goods.
  • Storage goods are understood to mean natural substances of vegetable or animal origin or processed products thereof which are of natural origin, and for which long-term protection is desired.
  • Storage goods of vegetable origin for example plants or plant parts, such as stems, leaves, tubers, seeds, fruits, grains, can be protected freshly harvested or after processing by (pre)drying, moistening, comminuting, grinding, pressing or roasting.
  • Storage goods also include timber, both unprocessed, such as construction timber, electricity poles and barriers, or in the form of finished products, such as furniture.
  • Storage goods of animal origin are, for example, hides, leather, furs and hairs.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I may prevent adverse effects, such as rotting, decay, discoloration, decoloration or formation of mould.
  • Micro-organisms capable of degrading or altering the industrial materials include, for example, bacteria, fungi, yeasts, algae and slime organisms.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I preferably act against fungi, especially moulds, wood-discoloring and wood-destroying fungi (Ascomycetes, Basidiomycetes, Deuteromycetes and Zygomycetes), and against slime organisms and algae.
  • micro-organisms of the following genera Altemaria, such as Alternaria tenuis; Aspergillus, such as Aspergillus niger; Chaetomium, such as Chaetomium globosum; Coniophora, such as Coniophora puetana; Lentinus, such as Lentinus tigrinus; Penicillium, such as Penicillium glaiicum; Polyporus, such as Polyporus versicolor; Aureobasidium, such as Aureobasidium pulhilans; Sclerophoma, such as Sclerophoma pityophila; Trichoderma, such as Trichoderma viride; Ophiostoma spp., Ceratocystis spp., Humicola spp., Petriella spp., Trichurus spp., Coriolus spp., Gloeophylhim spp., Pleurotus spp.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can be used also to control important fungal pathogens in fish and Crustacea farming, e.g. saprolegnia diclina in trouts, saprolegnia parasitica in crayfish.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can therefore be used both in medical and in non- medical appl ications.
  • the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can be used as such, in the form of their formulations or the use forms prepared therefrom, such as ready-to-use solutions, suspensions, wettable powders, pastes, soluble powders, dusts and granules.
  • Application is accomplished in a customary manner, for example by watering, spraying, atomizing, broadcasting, dusting, foaming, spreading-on and the like. It is also possible to deploy the active ingredients by the ultra-low volume method or to inject the active ingredient preparation/the active ingredient itself into the soil. It is also possible to treat the seed of the plants.
  • plants and their parts in accordance with the invention, preferably with wild plant species and plant cultivars, or those obtained by. ' conventional biological breeding methods, such as crossing or protoplast fusion, and also parts thereof.
  • transgenic plants and plant cultivars obtained by genetic engineering methods if appropriate in combination with conventional methods (Genetically Modified Organisms), and parts thereof are treated.
  • the terms "parts” or “parts of plants” or “plant parts” have been explained above. More preferably, plants of the plant cultivars which are commercially available or are in use are treated in accordance with the invention.
  • Plant cultivars are understood to mean plants which have new properties ("traits”) and have been obtained by conventional breeding, by mutagenesis or by recombinant DNA techniques. They can be cultivars, varieties, bio- or genotypes.
  • the method of treatment according to the invention can be used in the treatment of genetically modified organisms (GMOs), e.g. plants or seeds.
  • GMOs genetically modified organisms
  • Genetically modified plants (or transgenic plants) are plants of which a heterologous gene has been stably integrated into genome.
  • heterologous gene essentially means a gene which is provided or assembled outside the plant and when introduced in the nuclear, chloroplastic or mitochondrial genome gives the transformed plant new or improved agronomic or other properties by expressing a protein or polypeptide of interest or by downregulating or silencing other gene(s) which are present in the plant (using for example, antisense technology, cosuppression technology, RNA interference - RNAi - technology or microRNA - miRNA - technology).
  • a heterologous gene that is located in the genome is also called a transgene.
  • a transgene that is defined by its particular location in the plant genome is called a transformation or transgenic event.
  • Plants and plant cultivars which are preferably to be treated according to the invention include all plants which have genetic material which impart particularly advantageous, useful traits to these plants (whether obtained by breeding and/or biotechnological means).
  • Plants and plant cultivars which are also preferably to be treated according to the invention are resistant against one or more biotic stresses, i.e. said plants show a better defense against animal and microbial pests, such as against nematodes, insects, mites, phytopathogenic fungi, bacteria, viruses and/or viroids.
  • Plants and plant cultivars which may also be treated according to the invention are those plants which are resistant to one or more abiotic stresses.
  • Abiotic stress conditions may include, for example, drought, cold temperature exposure, heat exposure, osmotic stress, flooding, increased soil salinity, increased mineral exposure, ozone exposure, high light exposure, limited availability of nitrogen nutrients, limited availability of phosphorus nutrients, shade avoidance.
  • Plants and plant cultivars which may also be treated according to the invention are those plants characterized by enhanced yield characteristics. Increased yield in said plants can be the result of, for example, improved plant physiology, growth and development, such as water use efficiency, water retention efficiency, improved nitrogen use, enhanced carbon assimilation, improved photosynthesis, increased germination efficiency and accelerated maturation.
  • Yield can furthermore be affected by improved plant architecture (under stress and non-stress conditions), including but not limited to, early flowering, flowering control for hybrid seed production, seedling vigor, plant size, internode number and distance, root growth, seed size, fruit size, pod size, pod or ear number, seed number per pod or ear, seed mass, enhanced seed filling, reduced seed dispersal, reduced pod dehiscence and lodging resistance.
  • Further yield traits include seed composition, such as carbohydrate content and composition for example cotton or starch, protein content, oil content and composition, nutritional value, reduction in anti-nutritional compounds, improved processability and better storage stability.
  • Plants that may be treated according to the invention are hybrid plants that already express the characteristic of heterosis or hybrid vigor which results in generally higher yield, vigor, health and resistance towards biotic and abiotic stresses).
  • Plants or plant cultivars which may be treated according to the invention are herbicide-tolerant plants, i.e. plants made tolerant to one or more given herbicides. Such plants can be obtained either by genetic transformation, or by selection of plants containing a mutation imparting such herbicide tolerance.
  • Plants or plant cultivars which may also be treated according to the invention are insect-resistant transgenic plants, i.e. plants made resistant to attack by certain target insects. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such insect resistance.
  • Plants or plant cultivars obtained by plant biotechnology methods such as genetic engineering which may also be treated according to the invention are tolerant to abiotic stresses. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such stress resistance.
  • Plants or plant cultivars obtained by plant biotechnology methods such as genetic engineering which may also be treated according to the invention show altered quantity, quality and/or storage-stability of the harvested product and/or altered properties of specific ingredients of the harvested product.
  • Plants or plant cultivars which may also be treated according to the invention are plants, such as cotton plants, with altered fiber characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered fiber characteristics.
  • Plants or plant cultivars which may also be treated according to the invention are plants, such as oilseed rape or related Brassica plants, with altered oil profile characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered oil profile characteristics. Plants or plant cultivars (that can be obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants, such as oilseed rape or related Brassica plants, with altered seed shattering characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered seed shattering characteristics and include plants such as oilseed rape plants with delayed or reduced seed shattering.
  • Plants or plant cultivars which may also be treated according to the invention are plants, such as tobacco plants, with altered post-translational protein modification patterns.
  • the compounds of Formula 3 and 3A can be prepared by one or more of the following methods and variations as described in Schemes 1 - 13.
  • the definitions of J, G, Z, Q and n in the compounds of Formula 1 -24 below are as defined above in the detailed description unless otherwise noted.
  • the preparation of a compound of Formula 3 or 3a involves coupling of an acid of Formula 1 or la respectively with an amine of Formula 2 (or its acid salt) in the presence of a dehydrative coupling reagent such as dicyclohexylcarbodiimide (DCC) or l -(3-dimethylaminopropyl)-3- ethyicarbodiimide hydrochloride (EDC) O-benzotriazol-l-yl-tetramethy!uronium hexafluoro-phosphate (HBTU) or l -[bis(dimethylamino)methylene]- l H- l ,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU).
  • DCC dicyclohexylcarbodiimide
  • EDC l -(3-dimethylaminopropyl)-3- ethyicarbodiimide hydrochlor
  • Polymer-supported reagents such as polymer-bound cyclohexylcarbodi imide can also be used as coupling agent.
  • the reaction is typically carried out at 0 to 40 °C in a solvent such as dichloromethane or acetonitrile or N, N-dimethylformamide in the presence of a base such as triethylamine or diisopropylethylamine.
  • the compound of formula 3a can be obtained from the compound of Formula 3 by thiating the compound of Formula 3 using a thiating reagent such as phosphorus pentasulfide or 2, 4-bis (4- mefhoxyphenyl)-l, 3-dithia-2, 4-diphosphetane-2, 4-disulfide (Lawesson's reagent).
  • a thiating reagent such as phosphorus pentasulfide or 2, 4-bis (4- mefhoxyphenyl)-l, 3-dithia-2, 4-diphosphetane-2, 4-disulfide (Lawesson's reagent).
  • R 4 CH 2 COOH wherein R 4 is a heterocycl ic ring linked through nitrogen can be prepared by reacting the corresponding R 4 H compound with a halo acetic acid or ester in the presence of a base; followed by hydrolysis.
  • the amine compound of Formula 2 can be prepared from the protected amine compound of Formula 4 wherein Y i is an amine-protecting group.
  • the compound of Formula 4 is converted into the compound of Formula 2 by a suitable method for removing protecting groups described in the literature (Protective Groups in Organic Synthesis"; Theodora W. Greene, Peter G. M. Wuts; Wiley-Interscience; Third Edition; 1999; 494-653).
  • protecting groups described in the literature (Protective Groups in Organic Synthesis"; Theodora W. Greene, Peter G. M. Wuts; Wiley-Interscience; Third Edition; 1999; 494-653).
  • tert-Butoxycarbonyl and benzyloxycarbonyl protecting groups can be removed in an acidic medium for example by using hydrochloric acid or trifluoroacetic acid.
  • Acetyl protecting groups can be removed under basic conditions for example by using potassium carbonate or cesium carbonate.
  • Benzylic protecting groups can be removed hydrogenolytically by using hydrogen in the presence of a catalyst for example palladium on activated carbon.
  • the compound of Formula 2 is separated from the reaction mixture by one of the customary separation techniques. If necessary, the compounds are purified by recrystallization or chromatography, or can, if desired, also be used in the next step without prior purification. It is also possible to isolate the compound of Formula 2 as a salt, for example as a salt of hydrochloric acid or of trifluoroacetic acid.
  • a compound of Formula 4 wherein J-Q contains amine as one of the substituent involves coupling of an acid of Formula 5 with an amine of J-Q (or its acid salt) in the presence of a dehydrative coupling reagent such as dicyclohexylcarbodiimide (DCC) or 1 -(3-dimefhylaminopropyl)-3- etbylcarbodiimide hydrochloride (EDC) O-benzotriazol-l-yl-tetramethyluronium hexafluoro-phosphate (HBTU) or l -[Bis(dimethylamino)methylene]- l H- l ,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU).
  • DCC dicyclohexylcarbodiimide
  • EDC EDC
  • HBTU O-benzotriazol-l-yl-tetramethyluronium
  • Polymer-supported reagents such as polymer-bound cyclohexylcarbodiimide can also be used as coupling agent.
  • the reaction is typically carried out at 0 to 40 oC in a solvent such as dichloromethane or acetonitrile or N, N-dimethylformamide in the presence of a base such as triethylamine or diisopropylethylamine.
  • the compound of Formula 5 can be prepared by hydrolyzing a compound of Formula 6 using a base or an acid.
  • Preferred bases for the conversion of the compound of Formula 6 into the compound of Formula 5 are sodium hydroxide, lithium hydroxide, potassium hydroxide and the like.
  • Preferred acids for the conversion of the compound of Formula 6 into the compound of Formula 5 are hydrochloride acid, sulfuric acid, acetic acid, trifluroroacetic acid and the like.
  • Preferred solvents for the hydrolysis reactions are water or ethanol or tetrahydrofuran.
  • a compound of Formula 6b can be prepared by a compound of Formula 7 with a compound of Formula 8 in the presence of a base.
  • Suitable bases for such reaction include sodium hydride or potassium carbonate and the reaction is carried out in a solvent such as N, N-dimethylformamide or acetonitrile at 0 to 80 °C.
  • Suitable leaving group Y 2 in the compound of Formula 8 include bromide, iodide, mesylate, triflate and the like, and the compound of Formula 8 can be prepared from the corresponding compounds wherein Y 2 is hydroxy, using general methods known in the art.
  • the compound of Formula J-Q can be prepared by reacting a compound of Formula 9 with ammonium carbamate in the presence of PhI(OAc) 2 in methanol.
  • Different solvents such as acetonitrile, toluene, tetrahydrofuran can also be used for the preparation of the compound of Formula J-Q conversion.
  • Ammonium acetate and ammonia in methanol solution is also suitable as a nitrogen-source for this kind of conversion.
  • a suitably substituted compound of Formula 11 was purchased commercially or can be prepared from the corresponding chloro derivatives using known methods in the literature. Suitable reagents for this conversion can be sulfuric acid or hydrochloric acid or sodium hydroxide. Please refer PCT Patent Application Publication WO2007/39563 WO2014/71044 Lavecchia; Berteina-Raboin; crizt, and Tetrahedron Letters, 2004, 45, 35, 6633-6636.
  • the compound of Formula 11 can be further functionalized using known methods in the literature like chlorination, bromination, trifluromethylation to obtain appropriately substituted heterocyclic ring like pyridone (refer Formula 12).
  • a substituted heterocyclic ring containing a pyridone-l ike moiety can be acylated by reacting with an alkyl ester containing a suitable leaving group such as halogen or mesylate or tosylate in the presence of a base such as potassium carbonate or cesium carbonate in a polar solvent such as N, N-dimethylformamide or NMP with or without heating to obtain the compound of Formula 13.
  • a base such as potassium carbonate or cesium carbonate
  • a polar solvent such as N, N-dimethylformamide or NMP
  • mixtures of O- and N- alkylated products are obtained and the two regio-isomeric products can be separated by means of silica gel or reverse phase chromatography.
  • the addition of l ithium salts, for example lithium chloride to the reaction mixture can be employed to favor N-alkylation over O-alkylation.
  • the obtained aikyl ester can be further hydrolyzed to the corresponding acids by heating or stirring at room temperature in the presence of lithium hydroxide or sodi um hydroxide in solvents like ethanol or water to obtain the novel compound with Formula l a.
  • the preparation of a compound of Formula 15 can be achieved by reacting substituted acetoacetic ester with alkyl hydrazine of Formula 14 with excellent regioselectivity.
  • the compound of Formula 15 can then be selectively alkylated using alkyl halides with or without base to obtain a compound of Formula 16.
  • the compound of Formula 16 can be further functionalized using known methods in the literature like chlorination or bromination or trifluromethylation to obtain appropriately substituted compound of Formula 17.
  • the comound of Formula 17 can be further hydrolyzed by heating or stirring at room temperature in the presence of lithium hydroxide or sodium hydroxide or potassium hydroxide in solvents like ethanol or water to obtain the novel compound of Formula lb.
  • the compound of Formula lb can be used with or without converting it into corresponding acyl chloride.
  • a compound of Formula 18 and hydrazines are commercially available or can be prepared by methods known in the literature.
  • the comound of Formula 18 is reacted with hydrazines to form intermediate of Formula 19.
  • a compound of Formula 19a wherein R 1 is halogen can be prepared from the compound of Formula 19 (R 1 is H) by halogenating it with a halogenating reagent as shown in Scheme 1 1.
  • halogenating reagents known in the literature are suitable for this method including, for example, N- halosuccinimides (e.g., NBS, NCS, NIS), elemental halogen (e.g., Cl 2 , Br 2 , I 2 ), phosphorus oxyhalides, phosphorus trihalides, phosphorus pentahalides, thionyl chloride, sulfuryl chloride, bis(pyridine)iodonium(]) tetrafJuoroborate, tetramethylammonium iodide chloride, tetrafluoroborate and sulfur tetrafluoride.
  • N-halosuccinimides are particularly more suitable for such halogenation reactions.
  • the reaction is carried out in a suitable solvent such as N, N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane, acetic acid, chloroform, benzene, xylenes, chlorobenzene, tetrahydrofuran, 1 , 4 dioxane or the like.
  • a suitable solvent such as N, N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane, acetic acid, chloroform, benzene, xylenes, chlorobenzene, tetrahydrofuran, 1 , 4 dioxane or the like.
  • an organic base such as triethylamine, pyridine, N, N-dimethylaniline or the like can be added.
  • Catalyst such as N, N-dimethylforrnamide or 2, 2'-azobis (2- methylpropionitrile) (AIBN)
  • reaction temperatures range from about room temperature (e.g., 25 °C) to 1 50 °C.
  • room temperature e.g. 25 °C
  • Compounds of Formula 20 and 20a respectively can be prepared by treating the compounds of Formula 19 and 19a with ethyl bromo acetate preferably with bases as shown in the Scheme 1 1 .
  • the reaction is carried out in a suitable solvent such as N, N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane, tetrahydrofuran, acetone, 1 , 4 dioxane or the like.
  • a suitable solvent such as N, N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane, tetrahydrofuran, acetone, 1 , 4 dioxane or the like.
  • an organic base such as triethylamine, pyridine, or inorganic bases such as potassium carbonate, cesium carbonate, sodum carbonate or the like can be used.
  • the compounds of Formula 20 and 20a can be hydrolyzed by treating it with sodium hydroxide or lithium hydroxide or potassium hydroxide to obtain a compound of Formula lc as shown in the Scheme 1 1 .
  • Preferred solvents for the hydrolysis are water or ethanol or tetrahydrofuran.
  • a compound of Formula 12 and hydrazines (R 2 NHNH 2 ) are commercially available or can be prepared by methods known in the literature.
  • the preparation of a compound Formula 21 can be carried out using dimethyl sulphate in the presence of bases like potassium carbonate, cesium carbonate, sodium carbonate or the like as explained in Journal of Heterocyclic Chemistry, 1993, 30, 1 , 49-54.
  • the compound of Formula 21 can be reacted with hydrazine (R 2 NHNH 2 ) in protic solvents like ethanol or methanol to obtain a compound of Formula 22a.
  • a compound of Formula 22b wherein R 1 is halogen can be prepared from the compound of Formula 22a (R 1 is H) by halogenating it with a halogenating reagent as shown in Scheme 1 1.
  • a halogenating reagent known in the literature are suitable for this method including, for example, N- halosuccinimides (e.g., NBS, NCS, NIS), elemental halogen (e.g., Cl 2 , Br 2 , 1 2 ), phosphorus oxyhalides, phosphorus trihalides, phosphorus pentahalides, thionyl chloride, sulfuryl chloride, bis(pyridine)iodonium(I) tetrafluoroborate, tetramethylammonium iodide chloride, tetrafluoroborate and sulfur tetrafluoride.
  • N- halosuccinimides e.g., NBS, NCS, NIS
  • elemental halogen e.g., Cl
  • N-halosuccinimides are particularly more suitable for such halogenation reactions.
  • the reaction is carried out in a suitable solvent such as N, N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane, acetic acid, chloroform, benzene, xylenes, chlorobenzene, tetrahydrofuran, 1 , 4 dioxane or the like.
  • a suitable solvent such as N, N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane, acetic acid, chloroform, benzene, xylenes, chlorobenzene, tetrahydrofuran, 1 , 4 dioxane or the like.
  • an organic base such as triethylamine, pyridine, N, N-dimethylaniline or the like can be added.
  • Catalyst such as N, N-dimethylforrnamide or 2, 2'-azobis (2- methylpropionitrile) (AIBN) can also be used to catalyze such reaction.
  • reaction temperatures range from about room temperature (e.g., 25 °C) to 1 50 °C.
  • room temperature e.g. 25 °C
  • Compounds of Formula 23a and 23b can be prepared by treating the compounds of Formula 22a and 22b, with ethyl bromo acetate preferably with bases as shown in the Scheme 12.
  • the reaction is carried out in a suitable solvent such as N, N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane, tetrahydrofuran, acetone, 1 , 4 dioxane or the like.
  • a suitable solvent such as N, N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane, tetrahydrofuran, acetone, 1 , 4 dioxane or the like.
  • an organic base such as triethylamine, pyridine, or inorganic bases such as potassium carbonate, cesium carbonate, sodum carbonate or the l ike can be used.
  • Compounds of Formula 23a and 23b can be hydrolyzed by treating it with sodium hydroxide or lithium hydroxide or potassium hydroxide to obtain a compound of Formula la as shown in the scheme 12.
  • Preferred solvents for the hydrolysis are water or ethanol or tetrahydrofuran.
  • Substituted compounds of Formula 1 1 can be further functionalized using known methods in the literature like chlorination, Bromination, Trifluromethylation to get appropriately substituted heterocyclic ring like Pyridone (Formula 1 2)
  • References for the said transformations are Zhang, Pei-Zhi et al Tetrahedron, 2016,72(23), 3250-3255; Canibano; Rodriguez; Santos; Sanz-Tejedor; Carreno; Gonzalez; Garcia-Ruano Synthesis, 2001, 14,21 75 - 21 79, PCT Patent Application Publication WO2004/50637.
  • a substituted functional ized heterocyclic ring containing a pyridone-like moiety can be alkylated by reaction with an alkyl ester containing a suitable leaving group such as halogen, mesylate or tosylate, in the presence of a base such as Ag 2 C0 3 or Cs 2 C0 3 , in a polar sol!vent such as N, N-dimethylformamide or NMP, or non-polar solvent such as toluene, xylene with or without heating.to get the compound of Formula 24.
  • a polar sol!vent such as N, N-dimethylformamide or NMP, or non-polar solvent such as toluene, xylene with or without heating.
  • the addition of lithium salts, for example LiCl, to the reaction mixture can be employed to favor N- vs. O- alkylation.
  • the obtained alkyl ester can be further hydrolyzed to the corresponding acids by heating or stirring at room temperature in the presence of Lithium hydroxide or sodium hydroxide in solvents l ike ethanol, water to get the novel compounds with formula 1 .
  • synthesis of a compound of Formula 25 involves simple one-pot aromatic ethyl ester reduction into the corresponding alcohol using NaBH 4 -MeOH system.
  • the aromatic alcohols were obtained by the method explained in the ARKIVOC, 2006, 128- 133, involving the reduction of aromatic ethyl esters in 1 5-60 minutes after refluxing in THF.
  • the respective alcohol products were isolated after aqueous workup in good yield.
  • a compound of Formula 26 can be prepared by bromination of the compound of Formula 25 using CBr /PPh .
  • PBr 3 can also be used as brominating agent.
  • a compound of Formula 27 can be synthesised by treating the compound of Formula 26, with sulfoximine (J-Q) in the presence of a base like K'Obu, NaH, and K 2 C0 3 in solvents like DMF and DMSO.
  • J-Q sulfoximine
  • Synthesis of a compound of Formula 28 can be achieved by treating the compound of Formula 5 and suitable J-Q in presence of triethylamine and diphenylphosphoryl azide (DPPA) as a source of azide in solvents like toluene.
  • DPPA diphenylphosphoryl azide
  • Step A Preparation of ethyl 2-bromo-l,3-thiazole-4-carboxylate
  • Step B Preparation of ethyl 2-(l-(tert-butoxycarbonyl)-l,2,3,6-tetrahydropyridin-4-yl)thiazole-4- carboxylate
  • the reaction mixture was heated to 85 °C for 12 h.
  • the reaction mixture was cooled to 25 °C, filtered through celite bed and washed with methanol.
  • the filtrate was concentrated under reduced pressure and the residue obtained after concentration was purified by column chromatography using 45% ethyl acetate in hexane as an eluent to obtain ethyl 2-( 1 -(tert-butoxycarbonyl)- l ,2,3,6-tetrahydropyridin-4-yl)thiazole-4-carboxylate (50 g, 55% yield).
  • Step C Preparation of ethyl 2-(l-(tert-butoxycarbonyl)piperidin-4-yl)thiazole-4-carboxylate
  • Step D Preparation of 2-(l-(tert-butoxycarbonyl)piperidin-4-yl)thiazole-4-carboxylic acid
  • Step E Preparation of tert-butyl 4-(4-(((2,6-difluorophenyl)(methyl)(oxo)- ⁇ 6 - sulfanylidene)carbamoyI)thiazol-2-yl)piperidine-l-carboxylate
  • Step F Preparation of N-((2,6-difluorophenyI)(methyl)(oxo) ⁇ 6 -sulfanylidene)-2-(piperidin-4-yI) thiazole-4-carboxamide
  • Step G Preparation of N-((2,6-difluorophenyl)(methyI)(o o)- ⁇ 6 -sulfanylidene)-2-(l-(2-(5-methyl-3- (trifluoromethyl)-lH-pyrazol-l-yI)acetyl)piperidin-4-y])thiazole-4-carboxamide (Compound 15)
  • 2-(5-methyl-3-(trifluoromethyl)-l H-pyrazol- l -yl)acetic acid 129 mg, 0.6 mmol
  • N, N-dimethy!formamide 5 mL
  • l -[bis(dimethylamino)methylene]- l H-l ,2,3-triazolo[4,5-b]pyridinium 3- oxid hexafluorophosphate HATU
  • N-((3-bromophenyl)(methyl)(oxo) ⁇ 6 -sulfanylidene)-2-(pipendin-4-yl)thiazole-4- carboxamide 0.3 g, 0.6 mmol
  • N, N-dimethylformamide 8 mL
  • N, N-di isopropylethylamine 0.5 mL, 3.0 mmol
  • N-((2,6-dimethylphenyl)(ethyl)(oxo) ⁇ 6 -sulfanylidene)-2-(piperidin-4-yl)thiazole-4- carboxamide 0.3 g, 0.6 mmol
  • N, N-dimethylformamide 4 mL
  • N, N-diisopropylethylamine 6 mL, 3.2 mmol
  • Step B Preparation of (2,6-difluorophenyl)(imino)(methyl)-X 6 -siiIfanone
  • Step A Preparation of (2,6-dimethyIphenyI)(ethyl)sulfane
  • 2,6-dimethylbenzenethiol 1 .0 g, 7.2 mmol
  • triethylamine 1 .0 mL, 7.2 mmol
  • 2,6-dimethylbenzenethiol 1 .0 g, 7.2 mmol
  • Step B Preparation of (2,6-dimethylphenyl)(ethyl)(imino)- 6 -suIfanone
  • Step A Preparation of tert-butyl 4-(4-(bromomethyl)thiazol-2-yl)piperidine-l-carboxyIate
  • Step B Preparation of tert-butyl 4-(4-((((3-bromophenyl)(methy])(oxo)- 6 - sulfaneylidene)amino)methyl)thiazol-2-yl)piperidine-l-carboxyIate
  • tert-butyl 4-(4-(bromomethyl)thiazol-2-yl)piperidine- l -carboxylate (0.71 g, 2 mmol)
  • 3- bromophenyl)(imino)(methyl)- 6 -sulfanone (0.47g, 2 mmol) in dimethylformamide (20 mL) at 0 °C
  • potassium tert-butoxide (0.34 g, 3 mmol
  • the resulting reaction mixture was stirred at 0 °C for 2 h.
  • the reaction mixture was quenched with ice ( 10 g) and poured into a mixture of ethyl acetate (200 mL) and water ( 1 50 mL). Ethyl acetate and water layers were separated and the aqueous layer was extracted thrice with ethyl acetate (200 mL). The combined ethyl acetate layer was dried over anhydrous sodium sulphate, filtered, and concentrated.
  • Step C Preparation of (3-bromophenyl)(methyl)(((2-(piperidin-4-yl)thiazol-4-yl)methyl)imino)- 6 - sulfanone
  • Step E Preparation of (3-bromophenyJ)(met yl)(((2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazol-4-yI)methyl)imino)-X 6 -sulfanone
  • Step A Preparation of tert-butyl 4-(4-(3-((4-bromophenyl) (methyl) (oxo)- 6 -sulfanylidene) ureido) thiazol-2-yl) piperidine-l-carboxylate
  • tert-butyl 4-(4-(azidocarbonyl) thiazol-2-yl) piperidine-l -carboxylate was dried over anhydrous sodium sulphate and concentrated to obtain tert-butyl 4-(4-(azidocarbonyl) thiazol-2-yl) piperidine-l -carboxylate.
  • tert-butyl 4-(4-(azidocarbonyl)thiazol-2-yl)piperidine- l -carboxylate and (4- bromophenyl)(imino)(methyl) ⁇ 6 -sulfanone were taken up in acetonitrile (20 mL) and heated to 90 °C for 1 6 h.
  • Step B Preparation of l-((4-bromophenyl) (methyl) (oxo) ⁇ 6 -sulfanylidene)-3-(2-(piperidin-4-yl) thiazol-4-yl) urea 2, 2, 2-trifluoroacetate
  • a solution of tert-butyl 4-(4-(3-((4-bromophenyl) (methyl) (oxo)- 6 -sulfanylidene) ureido) thiazol-2- yl) piperidine- l -carboxylate ( 1 g, 1.8 mmol) in dichloromethane ( 10 mL), was added trifluoroacetic acid (4.2 mL, 55 mmol).
  • Step C l-(2-(l -(2-(3, 5-bis (difluoromethyl)-lH-pyrazol-l-yl) acetyl) piperidin-4-yl) thiazoI-4-yl)-3- ((4-bromophenyl) (methyl) (oxo)- '-sulfanylidene) urea
  • the resulting reaction mixture was stirred at 25 °C for 2 h.
  • the reaction mixture was diluted with cold water (50 mL) and extracted twice with ethyl acetate (50 mL).
  • the ethyl acetate layer was washed twice with cold water (50 mL), dried over anhydrous sodium sulphate and 5 concentrated under reduced pressure.
  • the product was purified by column chromatography using 100% ethyl acetate as an eluent to obtain l-(2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin- 4-yl)thiazol-4-yl)-3-((4-bi mophenyl)(methyl)(oxo)- 6 -sulfanylidene)urea (200 mg, 0.3 mmol, 45% yield).
  • GREENHOUSE Compounds were dissolved in 2% DMSO/Acetone & then mixed with water to calibrated spray volume of 50 mL. This 50 mL spray solution was poured into the spray bottles for further applications.
  • healthy young Tomato plants raised in the greenhouse were sprayed with active compound preparation at the stated application rates inside the spray cabinets using hallow-cone nozzles.
  • the plants were inoculated with sporangial suspension (Cold sterile water) containing 0.24x 1 0 6 Phytophthora infestans inoculum.
  • Example B Plasmopara viticola test in Grape

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Abstract

The present invention relates to a compound selected from Formula (I) and its salts, metal complexes, N-oxides, isomers, and polymorphs: Formula (I) wherein E, Z, R3, n, G, J & Q have the meaning as defined in the description.

Description

TITLE
NOVEL FUNGICIDAL HETEROCYCLIC COMPOUNDS FIELD OF THE INVENTION:
The present invention relates to novel fungicidal heterocyclic compounds and its salts, metal complexes, N-oxides, enantiomers, stereoisomers and polymorphs thereof; compositions and methods of use of the compounds for controlling or preventing phytopathogenic micro-organisms.
BACKGROUND:
The control of damages to crops caused by phytopathogenic micro-organisms is extremely important in achieving high crop efficiency. For instance, plant disease damage to ornamental, vegetable, field, cereal, and fruit crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. Many products are commercially available to control such damages. The need continues for new compounds which are more effective, less costly, less toxic, and environmentally safer and/or have different modes of action. Certain oxazole-thiazole piperdine heterocyclic compounds having fungicidal properties have already been described in the literature, as for example, WO2008013622, WO2008013925, WO2009094407, WO2009094445, WO2010065579, WO2010123791 , WO201 1076699, WO201 1085170, WO2012020060, WO2012025557, WO2012055837, WO2012082580, WO2012104273, WO2013037768, WO2013098229, WO2013127784, WO2013127808, WO2014075873, WO2014075874, WO20141 18142, WO20141 18143, WO2014 ] 54530, WO2014179144, WO2014206896, WO201 5028457, WO2015144571 , WO2016024350, WO2016024434, WO201 7109858 and WO2017109855.
The effectiveness of the oxazole-thiazole piperdine heterocyclic compounds described in the prior art is satisfactory, but leaves something to be desired in various cases. Therefore, it is always of high interest in agriculture to use novel pest'icidal compounds in order to avoid and/or control the development of microorganisms such as fungal or bacterial pathogens or pests being resistant to known active ingredients. It is therefore of high interest to use novel compounds.
Surprisingly, it is now found that the compounds and compositions thereof of the present invention have the potential of overcoming drawbacks and are suitable for crop protection against phytopathogenic micro-organisms causing plant diseases. SUMMARY OF THE INVENTION:
The present invention relates to a compound selected from Formula I,
Figure imgf000003_0001
wherein the substituents are as defined in the description.
The present invention will now be described in detail in the description.
DETAILED DESCRIPTION OF THE INVENTION:
DEFINITIONS: The following definitions provided herein for the terminologies used in the present invention are for illustrative purpose only and in no manner limit the scope of the present invention.
As used herein, the terms "comprises", "comprising", "includes", "including", "has", "having", "contains", "containing", "characterized by" or any other variation thereof, are intended to cover a nonexclusive inclusion, subject to any limitation explicitly indicated. For example, a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process or method.
The transitional phrase "consisting of excludes any element, step or ingredient not specified. If in the claim, such would close the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase "consisting of appears in a clause of the body of a claim, rather than immediately fol lowing the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.
The transitional phrase "consisting essentially of is used to define a composition or method that includes materials, steps, features, components or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components or elements do not material ly affect the basic and novel characteristic(s) of the claimed invention. The term "consisting essentially of occupies a middle ground between "comprising" and "consisting of.
Further, unless expressly stated to the contrary, "or" refers to an inclusive "or" and not to an exclusive "or". For example, a condition A "or" B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
Also, the indefinite articles "a" and "an" preceding an element or component of the present invention are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore "a" or "an" should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.
Compounds of the present invention may be present either in pure form or as mixtures of different possible isomeric forms such as stereoisomers or constitutional isomers. The various stereoisomers include enantiomers, diastereomers, chiral isomers, atropisomers, conformers, rotamers, tautomers, optical isomers, polymorphs, and geometric isomers. Any desired mixtures of these isomers fall within the scope of the claims of the present invention. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other isomer(s) or when separated from the other isomer(s). Additionally, the person skilled in the art knows processes or methods or technology to separate, enrich, and/or to selectively prepare said isomers.
The term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" or -N(alkyl) or alkylcarbonylalkyl or alkylsuphonylamino includes straight-chain or branched Cj to C24 alkyl, preferably Ci to C ) 5 alkyl, more preferably Cj to C|0 alkyl, most preferably Q to C6 alkyl. Representative examples of alkyl include methyl, ethyl, propyl, 1 -methylethyl, butyl, 1 -methylpropyl, 2-methylpropyl, 1 , 1 -dimethyl ethyl, pentyl, 1 -methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1 - ethylpropyl, hexyl, 1 , 1 -dimethylpropyl, 1 ,2-dimethylpropyl, 1 -methylpentyl, 2-methylpentyl, 3- methylpentyl, 4-methylpentyI, 1 , 1 -dimethyl butyl, 1 ,2-dimethylbutyl, 1 ,3-dimethylbutyl, 2,2- dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1 -ethylbutyl, 2-ethylbutyl, 1 , 1 ,2-trimethylpropyl, 1 ,2,2-trimethylpropyl, 1 -ethyl-l -methylpropyl and l-ethyl-2-methylpropyl or the different isomers. If the alkyl is at the end of a composite substituent, as, for example, in alkylcycloalkyl, the part of the composite substituent at the start, for example the cycloalkyl, may be mono- or polysubstituted identically or differently and independently by alkyl. The same also applies to composite substituents in which other radicals, for example alkenyl, alkynyl, hydroxyl, halogen, carbonyl, carbonyloxy and the like, are at the end. The term "alkenyl", used either alone or in compound words includes straight-chain or branched C2 to C24 alkenes, preferably C2 to C 15 alkenes, more preferably C2 to C |0 alkenes, most preferably C2 to Cb alkenes. Representative examples of alkenes include ethenyl, 1 -propenyl, 2-propenyl, 1 -methylethenyl, 1 -butenyl, 2-butenyl, 3-butenyl, 1 -methyl- 1 -propenyl, 2-methyl-l-propenyl, l-methyl-2 -propenyl, 2-methyl-2- propenyl, 1 -pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1 -methyl- 1 -butenyl, 2-methyl- l -buteny!, 3- methyl- l -butenyl, l-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, l-methyl-3-butenyl, 2- methyl-3-butenyl, 3-methyl-3-butenyl, l , l -dimethyl-2-propenyl, 1 ,2-dimethyl-l -propenyl, l ,2-dimethyl-2 -propenyl, 1 -ethyl-l -propenyl, l-ethyl-2-propenyl, 1 -hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1 -methyl- 1 -pentenyl, 2-methyl- 1 -pentenyl, 3-methyl- 1 -pentenyl, 4-methyl- 1 -pentenyl, l -metbyl-2- pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, l-methyI-3-pentenyl, 2-methyl- 3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, l -methyl-4-pentenyl, 2-methyl-4-pentenyl, 3- methyl-4-pentenyl, 4-methyl-4-pentenyl, l , l -dimethyl-2-butenyl, l,l-dimethyl-3-butenyl, 1 ,2-dimethyl-l- butenyl, l ,2-diinethyl-2-butenyl, ] ,2-dimethy!-3-butenyl, 1 ,3-dimethyl- ) -butenyl, l,3-dimethyl-2-butenyl, l,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-l -butenyl, 2,3-dimethyl-2-butenyl, 2,3- dimethyl-3-butenyl, 3,3-dimethyl-l-butenyl, 3,3-dimethyl-2-butenyl, 1 -ethyl- l -butenyl, 1 -ethyl-2-butenyl,
1- ethyl-3-butenyl, 2-ethyl- 1 -butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, l,l,2-trimethyl-2-propeny!, 1 - ethyl-l-methyl-2-propenyl, l-ethyl-2-methyl-l-propenyl and l-ethyl-2-methyl-2-propenyl and the different isomers. "Alkenyl" also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl . This definition also applies to alkenyl as a part of a composite substituent, for example haloalkeny! and the like, unless defined specifically elsewhere.
The term "alkynyl", used either alone or in compound words includes straight-chain or branched C2 to C24 alkynes, preferably C2 to C ,5 alkynes, more preferably C2 to C]0 alkynes, most preferably C2 to Cf) alkynes. Representative examples of alkynes include ethynyl, 1 -propynyl, 2-propynyl, 1 -butynyl, 2- butynyl, 3-butynyl, l -methyl-2-propynyl, 1 -pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, l-methyl-2- butynyl, l-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-l-butynyl, l , ] -dimethyl-2-propynyl, 1 -ethyl -
2- propynyl, 1 -hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, l -methyl-2-pentynyl, l-methyl-3- pentynyl, l -methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyI-4-pentynyl, 3-methyl-l-pentynyl, 3- methyl-4-pentynyl, 4-methyl-l-pentynyl, 4-methyl-2-pentynyl, l , l -dimethyl-2-butynyl, l,l-dimethyl-3- butynyl, l,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-l-butynyl, l-ethyl-2-butynyl, 1- ethyl-3-butynyl, 2-ethyl-3-butynyl and l -ethyl-l-methyl-2-propynyl and the different isomers. This definition also applies to alkynyl as a part of a composite substituent, for example haloalkynyl etc., unless specifically defined elsewhere. "Alkynyl" can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.
The term "cycloalkyl" means alkyl closed to form a ring. Representative examples include but are not l imited to cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. This definition also applies to cycloalkyl as a part of a composite substituent, for example cycloalkylalkyl etc., unless specifically defined elsewhere. The term "cycloalkenyl" means alkenyl closed to form a ring including monocyclic, partially unsaturated hydrocarbyl groups. Representative examples include but are not limited to cyclopentenyl and cyclohexenyl. This definition also applies to cycloalkenyl as a part of a composite substituent, for example cycloalkenylalkyl etc., unless specifically defined elsewhere.
The term "cycloalkynyl" means alkynyl closed to form a ring including monocyclic, partially unsaturated groups. This definition also applies to cycloalkynyl as a part of a composite substituent, for example cycloalkynylalkyl etc., unless specifically defined elsewhere.
The terms "cycloalkoxy", "cycloalkenyloxy" and the like are defined analogously. Representative examples of cycloalkoxy include cyclopropyloxy, cyclopentyloxy and cyclohexyloxy. This definition also applies to cycloalkoxy as a part of a composite substituent, for example cycloalkoxy alkyl etc., unless specifically defined elsewhere.
The term "halogen", either alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different.
Non-limiting examples of "haloalkyl" include chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1 -chloroethyl, 1 -bromoethyl, 1 -fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2- fluoroethyl, 2,2,2-trichIoroethyl, pentafluoroethyl, 1 , l -dichloi -2,2,2-trifluoroethyl, and 1 , 1 , 1 - trifluoroprop-2-yl. This definition also applies to haloalkyl as a part of a composite substituent, for example haloalkylaminoalkyl etc., unless specifically defined elsewhere.
The terms "haloalkenyl" and "haloalkyny!" are defined analogously except that, instead of alkyl groups, alkenyl and alkynyl groups are present as a part of the substituent.
The term "haloalkoxy" means straight-chain or branched alkoxy groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified 'above. Non-limiting examples of haloalkoxy include chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fiuoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1 -chloroethoxy, 1 -bromoethoxy, 1 -fluoroethoxy, 2-fluoroethoxy, 2,2- difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloiO-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro- 2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy and l,l,l-trifluoropiOp-2-oxy. This definition also applies to haloalkoxy as a part of a composite substituent, for example haloalkoxyalkyl etc., unless specifical ly defined elsewhere.
The term "haloalkylthio" means straight-chain or branched alkylthio groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above. Non-limiting examples of haloalkylthio include chloromethylthio, bromomethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio, dichlorofluoromethylthio, chlorodifiuoromethylthio, 1 -chloroethylthio, 1 -bromoethylthio, 1 - fluoroethylthio, 2-fluoroethylthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2-chloro-2- fluoroethylthio, 2-chloro-2,2-difluoroethylthio, 2,2-dichloro-2-fluoroethylthio, 2,2,2-trichloroethylthio, pentafluoroethylthio and l,l,l-trifluoroprop-2-ylthio. This definition also applies to haloalkylthio as a part of a composite substituent, for example haloalkylthioalkyl etc., unless specifically defined elsewhere. Examples of "haloalkylsulfinyl" include CF3S(0), CC13S(0), CF3CH2S(0) and CF3CF2S(0). Examples of "haloalkylsulfonyl" include CF3S(0)2, CC13S(0)2, CF3CH2S(0)2 and CF3CF2S(0)2.
The term "hydroxy" means -OH, the term "amino" means -NRR, wherein R can be H or any possible substituent such as alkyl. The term "carbonyl" means -C(O)- , the term "carbonyloxy" means -OC(O)-., the term "sulfinyl" means S(O), and the term "sulfonyl" means S(0)2 '
The term "alkoxy" used either alone or in compound words included Cj to C24 alkoxy, preferably C | to C i 5 alkoxy, more preferably C , to C10 alkoxy, most preferably Q to C6 alkoxy. Examples of alkoxy include methoxy, ethoxy, propoxy, 1 -methyl ethoxy, butoxy, 1 -methylpropoxy, 2-methylpropoxy, 1 , 1 - dimethylethoxy, pentoxy, 1 -methylbutoxy, 2-methylbutoxy, 3 -methyl butoxy, 2,2-dimethylpropoxy, 1 - ethylpropoxy, hexoxy, 1 , 1 -dimethylpropoxy, 1 ,2-dimethylpropoxy, 1 -methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methyl pentoxy, 1 , 1 -dimethylbutoxy, 1 ,2-dimethylbutoxy, 1 ,3-dimethylbutoxy, 2,2- dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1 -ethyl butoxy, 2-ethylbutoxy, 1 , 1 ,2- trimethylpropoxy, 1 ,2,2-trimethylpropoxy, 1 -ethyl- 1 -methylpropoxy and l-ethyl-2-methylpropoxy and the different isomers. This definition also applies to alkoxy as a part of a composite substituent, for example haloalkoxy, alkynylalkoxy, etc., unless specifically defined elsewhere.
The term "alkoxyalkyl" means alkoxy substitution on alkyl . Examples of "alkoxyalkyl" include CH3OCH2; CH3OCH2CH2; CH3CH2OCH2; CH3CH2CH2CH2OCH2 and CH3CH2OCH2CH2. The term "alkoxyalkoxy" means alkoxy substitution on alkoxy.
The term "alkylthio" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, propylthio, 1 -methylethylthio, butylthio, 1 -methylpropylthio, 2-methylpropylthio, 1 , 1 -dimethylethylthio, pentylthio, 1 -methylbiitylthio, 2-methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio, 1 - ethylpropylthio, hexylthio, 1 , 1 -dimethylpropylthio, 1 ,2-dimethylpropylthio, 1 -methylpentylthio, 2- methylpentylthio, 3-methylpentylthio, 4-methylpentylthio, 1 , 1 -dimethylbutylthio, 1 ,2-dimethylbutylthio, 1 ,3-dimethylbutylthio, 2,2-dimethylbutylthio, 2,3-dimethylbutylthio, 3,3-dimethylbutylthio, 1 - ethylbutylthio, 2-ethylbutylthio, 1 , 1 ,2-trimethylpropylthio, 1 ,2,2-tri methyl propylthio, 1 -ethyl- 1 - methylpropylthio and l-ethyl-2-methylpropyIthio and the different isomers.
The terms "halocylcoalkyl", "halocylcoalkenyl", "alkylcycloalkyl", "cycloalkylalkyl", "cycloalkoxyalkyl", "alkylsulfinylalkyl", "alkylsulfonylalkyl", "haloalkylcarbonyl",
"cycloalkylcarbonyl", "haloalkoxylalkyl", and the like, are defined analogously to the above examples.
The term "alkylthioalkyl" means alkylthio substitution on alkyl. Non-limiting examples of "alkylthioalkyl" include CH2SCH2; CH2SCH2CH2; CH3CH2SCH2; CH3CH2CH2CH2SCH2; CH3CH2SCH2CH2 and the like or different isomers. The term "alkylthioalkoxy" denotes alkylthio substitution on alkoxy. The term "cycloalkylalkylamino" denotes cycloalkyi substitution on alkyl amino.
The terms "alkoxyalkoxyalkyl", "alkylaminoalkyl", "dialkylaminoalkyl", "cycloalkylaminoalkyl", "cycloalkylaminocarbonyl" and the like, are defined analogously to "alkylthioalkyl" or cycloalkylalkylamino.
The term "alkoxycarbonyl" is an alkoxy group bonded to a skeleton via a carbonyl group (-CO-). This definition also applies to alkoxycarbonyl as a part of a composite substituent, for example cycloalkylalkoxycarbonyl and the like, unless specifically defined elsewhere.
The term "alkoxycarbonylalkylamino" means alkoxy carbonyl substitution on alkyl amino. The term "alkylcarbonylalkylamino" means alkyl carbonyl substitution on alkyl amino. The terms alkylthioalkoxycarbonyl, cycloalkylalkylaminoaikyl and the like are defined analogously.
The term "alkylsulfinyl" means alkyl substitution on sulfinyl group. Non-l imiting examples of "alkylsu!finyl " include ; methylsulphinyl; ethylsulphinyl; propylsulphinyl; 1 -methylethylsulphinyl; butylsulphinyl ; 1 -methylpropylsulphinyl ; 2-methylpropylsulphinyl; 1 , 1 -dimethylethylsulphinyl; pentylsulphinyl ; 1 -methylbutylsu!phinyl ; 2-methylbutylsulphinyl; 3-methylbutylsulphinyl ; 2,2- dimethyl propylsulphinyl; l -ethylpropylsulphinyl; hexylsulphinyl; 1 , 1 -dimethyIpropyIsulphinyl; 1 ,2- dimethyl propylsulphinyl; 1 -methylpentyisulphinyl ; 2-methylpentylsulphinyl ; 3-methylpentylsulphinyl; 4- methylpentylsulphinyl; 1 , 1 -dimethylbutylsulphinyl; 1 ,2-dimethylbutylsulphinyl; 1 ,3- dimethylbutylsulphinyl; 2,2-dimethylbutylsulphinyI ; 2,3-dimethylbutylsulphinyl; 3,3- dimethylbutylsLilphinyl; 1 -ethyl butylsulphinyl; 2-ethylbutylsulphinyl; 1 , 1 ,2-trimethylpropylsulphinyl; 1 ,2,2-trimethyIpropylsulphinyI ; 1 -ethyl- l -methylpropylsulphinyl ; 1 -ethyI-2-methylpropyisulphinyl and the like or different isomers. The term "arylsulfinyl" i ncludes Ar-S(O), wherein Ar can be any carbocyle or heterocyicle. This definition also applies to alkylsulfinyl as a part of a composite substituent, for example haloalkylsulfinyl etc., unless specifically defined elsewhere. The term "alkyl sulfonyl" means alkyl substitution on sulfonyl group. Non-limiting examples of "alkylsulfonyl" include methylsulphonyl; ethylsulphonyl; propylsulphony! ; 1 -methylethylsulphonyl; butylsulphonyl ; 1 -methylpropylsulphonyl ; 2-methylpropylsulphonyl; 1 , 1 -dimethylethylsulphonyl; pentylsulphonyl; 1 -methylbutylsulphonyl; 2-methylbutylsulphonyl ; 3-methylbutylsulphonyl; 2,2- dimethylpropylsulphonyl ; 1 -ethylpropylsulphonyl; hexylsuiphonyl; 1 , 1 -dimethylpropyisuiphonyl; 1 ,2- dimethylpropyisuiphonyl; 1 -methylpentylsulphonyl; 2-methylpentylsulphonyl; 3-methylpentylsulphonyl; 4-methylpentylsLilphonyl ; 1 , 1 -dimethylbutylsulphonyl; 1 ,2-dimethylbutylsulphonyl; 1 ,3- dimethylbutylsulphonyl; 2,2-dimethylbutylsulphonyl; 2,3-dimethylbutyIsulphonyl; 3,3- dimethylbutylsulphonyl; 1 -ethylbutylsulphonyl; 2-ethylbutylsulphonyl; 1 , 1 ,2-trimethylpropylsulphonyl; 1 ,2,2-trimethylpropylsulphonyl ; 1 -ethyl-l -methylpropylsulphonyl; l-ethyl-2-methylpropylsulphonyl and the like or different isomers. The term "arylsulfonyl" includes Ar-S(=0)2, wherein Ar can be any carbocyle or heterocyicle. This definition also applies to alkylsulfonyl as a part of a composite substituent, for example alkylsulfonylalkyl etc., unless defined elsewhere.
The terms "alkylamino", "dialkylamino", and the l ike, are defined analogously to the above examples.
The term "carbocycle or carbocyclic" includes "aromatic carbocyclic ring system" and "nonaromatic carbocylic ring system" or polycyclic or bicyclic (spiro, fused, bridged, nonfused) ring compounds in which ring may be aromatic or non-aromatic (where aromatic indicates that the Hueckel rule is satisfied and non-aromatic indicates that the Hueckel rule is not statisfied).
The term "hetero" in connection with rings refers to a ring in which at least one ring atom is not carbon and which can contain heteroatoms independently selected from the group comprising of nitrogen, oxygen, sulfur, etc. The term "hetero" in connection with atom refer to an atom independently selected from nitrogen, sulfur, oxygen, etc.
The term "heterocycle" or "heterocycl ic" includes "aromatic heterocycle" or "heteroaryl ring system" and "nonaromatic heterocycle ring system" or polycyclic or bicyclic (spiro, fused, bridged, non-fused) ring compounds in which ring may be aromatic or non-aromatic, wherein the heterocycle ring contains at least one heteroatom selected from N, O,
Figure imgf000009_0001
and or C ring member of the heterocycle may be replaced by C(=0), C(=S), C(=CR*R*) and C(=NR*), * indicates integers. The term "non-aromatic heterocyle" includes fused or unfused three- to fifteen-membered, preferably three- to tweleve-membered, saturated or fully or partially unsaturated heterocycle, monocyclic or polycyclic (spiro, fused, bridged, nonfused) heterocycle wherein heteroatom is selected from the group of oxygen, nitrogen and sulphur; and if the ring contains more than one oxygen atom, they are not directly adjacent; Non-limiting examples of non-aromatic heterocyle include oxetanyl, oxiranyl; aziridinyl; thi iranyl, azetidinyl, thiethanyl, dithiethanyl, diazetidinyl, 2-tetrahydrofuranyl; 3-tetrahydrofuranyl; 2- tetrahydrothienyl; 3-tetrahydrothienyl; 2-pyrrolidinyl; 3-pyrrolidinyl; 3-isoxazolidinyl; 4-isoxazolidinyl; 5-isoxazolidinyl; 3-isothiazolidinyl ; 4-isothiazolidinyl; 5-isothiazolidinyI; 3-pyrazolidinyl; 4- pyrazolidinyl; 5-pyrazolidinyl; 2-oxazolidinyl; 4-oxazolidinyl; 5-oxazolidinyl; 2-thiazolidinyl; 4- thiazolidinyl; 5-thiazolidinyl; 2-imidazolidinyl; 4-imidazolidinyl; l ,2,4-oxadiazolidin-3-yl; 1,2,4- oxadiazol idin-5-yl ; l,2,4-thiadiazolidin-3-yl; 1 ,2,4-thiadiazolidin-5-yl; l,2,4-triazolidin-3-yl; 1,3,4- oxadiazolidin-2-yl; l,3,4-thiadiazolidin-2-yl; l ,3,4-triazolidin-2-yl; 2,3-dihydrofur-2-yl; 2,3-dihydrofur-3- yl; 2,4-dihydrofur-2-yl; 2,4-dihydrofur-3-yl; 2,3-dihydrothien-2-yl; 2,3-dihydrothien-3-yl; 2,4- dihydrothien-2-yl ; 2,4-dihydrothien-3-yl; 2-pyrrolin-2-yl; 2-pyrrolin-3-yl; 3-pyrrolin-2-yl; 3-pyrrolin-3- yl; 2-isoxazol in-3-yl; 3-isoxazolin-3-yl; 4-isoxazolin-3-yl; 2-isoxazolin-4-yl; 3-isoxazolin-4-yl; 4- isoxazolin-4-yl ; 2-isoxazolin-5-yl; 3-isoxazolin-5-yl; 4-isoxazolin-5-yl; 2-isothiazolin-3-yl; 3- isothiazolin-3-yl; 4-isothiazolin-3-yl; 2-isothiazolin-4-yl; 3-isothiazolin-4-yl; 4-isothiazolin-4-yl ; 2- isothiazolin-5-yl; 3-isothiazolin-5-yl; 4-isothiazolin-5-yl; 2,3-dihydropyrazol-l-yl; 2,3-dihydropyrazol-2- yl; 2,3-dihydropyrazol-3-yl; 2,3-dihydropyrazol-4-yl; 2,3-dihydropyrazol-5-yl; 3,4-dihydropyrazol-l-yl; 3,4-dihydropyrazol-3-yl ; 3,4-dihydropyrazol-4-yl ; 3,4-dihydropyrazol-5-yl; 4,5-dihydropyrazol-l-yl ; 4,5- dihydropyrazol-3-yl; 4,5-dihydropyrazol-4-yl; 4,5-dihydropyrazol-5-yl; 2,3-dihydrooxazol-2-yl; 2,3- dihydrooxazol-3-yl; 2,3-dihydrooxazol-4-yl; 2,3-dihydrooxazol-5-yl; 3,4-dihydrooxazol-2-yl; 3,4- dihydrooxazol-3-yl; 3,4-dihydrooxazol-4-yl; 3,4-dihydrooxazol-5-yl; 3,4-dihydrooxazol-2-yl; 3,4- dihydrooxazol-3-yl; 3,4-dihydrooxazol-4-yl; 2-piperidinyl; 3-piperidinyl; 4-piperidinyi; l,3-dioxan-5-yl; 2-tetrahydropyranyl; 4-tetrahydropyranyl; 2-tetrahydrothienyl; 3-hexahydropyridazinyl; 4- hexahydropyridazinyl ; 2-hexahydropyrimidinyl ; 4-hexahydropyrimidinyl; 5-hexahydropyrimidinyl; 2- piperazinyl; l,3,5-hexahydrotriazin-2-yl;l,2,4-hexahydrotriazin-3-yl; 2,3,4,5-tetrahydro[ l H]azepin-l - or - 2- or -3- or -4- or -5- or -6- or -7- yl; 3,4,5,6-tetra-hydro[2H]azepin-2- or -3- or -4- or -5- or -6- or-7-yl; 2,3,4,7-tetrahydrof l H]azepin- 1 - or -2- or -3- or -4- or -5- or -6- or-7- yl; 2,3,6,7-tetrahydro[ l H]azepin- l - or -2- or -3- or -4- or -5- or -6- or -7- yl; hexahydroazepin- 1 - or -2- or -3- or -4- yl, tetra- and hexahydrooxepinyl such as 2,3,4,5-tetrahydro[ l H]oxepin-2- or -3- or -4- or -5- or -6- or -7- yl; 2,3,4,7- tetrahydrof l H]oxepin-2- or -3- or -4- or -5- or -6- or -7- yl; 2,3,6,7-tetrahydro[ l H]oxepin-2- or -3- or -4- or -5- or -6- or -7- yl ; hexahydroazepin-1 - or -2- or -3- or -4- yl; tetra- and hexahydro- l ,3-diazepinyl; tetra- and hexahydro- 1 ,4-diazepinyl; tetra- and hexahydro- l ,3-oxazepinyl; tetra- and hexahydro- 1 ,4- oxazepinyl, tetra- and hexahydro- l ,3-dioxepinyl, tetra- and hexahydro- 1 ,4-dioxepinyl. This definition also applies to heterocyclyl as a part of a composite substituent, for example heterocyclylalkyl etc., unless specifical ly defined elsewhere.
The term "aromatic heterocycle or heteroaryi" includes fused or unfused three to fifteen membered, preferably three to tweleve membered, more preferably 5 or 6 membered; monocyclic or polycyclic unsaturated ring system, containing heteroatoms selected from the group of oxygen, nitrogen, sulphur, etc.
Non-limiting examples of 5 membered heteroaryi groups include fury], thienyl, pyrrolyl, isoxazo!yl, isothiazolyl, pyrazolyl, oxazolyl, thiazolyl, imidazolyl, 1,2,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4-triazolyl, 1,3,4-oxadiazolyl, 1,3,4-thiadiazolyl, 1,3,4-triazolyl, tetrazolyl; nitrogen-boiided 5-membered heteroaryi containing one to four nitrogen atoms, or benzofused nitrogen-bonded 5-membered heteroaryi containing one to three nitrogen atoms: 5-membered heteroaryi groups which, in addition to carbon atoms, may contain one to four nitrogen atoms or one to three nitrogen atoms as ring members and in which two adjacent carbon ring members or one nitrogen and one adjacent carbon ring member may be bridged by a buta-l,3-diene-l,4-diyl group in which one or two carbon atoms may be replaced by nitrogen atoms, where these rings are attached to the skeleton via one of the nitrogen ring members, for example (but not limited to) 1 -pyrrolyl, l -pyrazolyl, 1 ,2,4-triazol-l- yl, 1 -imidazolyl, 1 ,2,3-triazol-l-yl and 1 ,3,4-triazol-l-yl.
Non-limiting examples of 6 membered heteroaryi groups include 2-pyridinyl; 3-pyridinyl; 4-pyridinyl; 3- pyridazinyl; 4-pyridazinyl; 2-pyrimidinyl; 4-pyrimidinyl; 5-pyrimidinyl; 2-pyrazinyl; l,3,5-triazin-2-yl; l,2,4-triazin-3-yl; l,2,4,5-tetrazin-3-yl and the like.
Non-limiting examples of benzofused 5-membered heteroaryi include indol-l-yl ; indol-2-yl; indol-3-yl; indol-4-yl; indol-5-yl; indol-6-yl; indol-7-yl; benzimidazol-l-yl; benzimidazol-2-yl ; benzimidazol-4-yl; benzimidazol-5-yl; indazol-l-yl; indazol-3-yl; indazol-4-yl; indazol-5-yl ; indazol-6-yl ; indazol-7-yl; indazol-2-yl; l-benzofuran-2-yl; l-benzofuran-3-yl; l-benzofuran-4-yl; l-benzofuran-5-yl; 1 -benzofuran- 6- yl; l-benzofuran-7-yl; l-benzothiophen-2-yl; l-benzothiophen-3-yl; l-benzothiophen-4-yl; 1 - benzothiophen-5-yl; l-benzothiophen-6-yl; l-benzothiophen-7-yl; l,3-benzothiazol-2-yl; 1 ,3- benzothiazol- 4-yl; l,3-benzothiazol-5-yl; l,3-benzothiazol-6-yl; l,3-benzothiazol-7-yl; l,3-benzoxazol-2-yl; 1,3- benzoxazol-4-yl; l,3-benzoxazol-5-yl; l ,3-benzoxazol-6-yl; l,3-benzoxazol-7-yl and the like.
Non-limiting examples of benzofused 6-membered heteroaryi include quinol in-2-yl; quinolin-3-yl; quinolin-4-yl; quinolin-5-yl; quinolin-6-yl; quinolin-7-yl ; quinolin-8-yl; isoquinolin-l-yl; isoquinolin-3-yl; isoquinolin-4-yl ; isoquinolin-5-yl ; isoquinolin-6-yl; isoquinolin-7-yl ; isoquinolin-8-yl and the like. This definition also applies to heteroaryl as a part of a composite substituent, for example heteroarylalkyl etc., unless specifically defined elsewhere.
The term "aromatic heterocycle/heteroaryl" indicates that the Hueckel 's rule is satisfied and the term "non-aromatic heterocycle" indicates that the Hueckel 's rule is not satisfied. The term "Huckel 's rule" has the same meaning as defined and elaborated in Organic Chemistry by Jonathan Clayden, Nick Geeves, Stuart Warren.
The term "alkylsilyl" means branched and/or straight-chain alkyl radicals attached to a silicon atom. Non- limiting examples of alkylsilyl include trimefhylsilyl, triethylsilyl, t-butyl-dimethylsilyl and the like or different isomers. The term "haloalkylsilyl" means at least one alkyl radicals of alkylsilyl is partially or fully substituted with halogen atoms which may be the same or different.
The term "alkoxyalkylsilyl" denotes at least one alkyl radical of alkylsilyl is substituted with one or more alkoxy radicals which may be the same or different. The term "alkylsilyloxy" denotes an alkylsilyl moiety attached through oxygen. The term "alkyl carbonyl" means alkyl group substituted on the carbonyl group. Non-limiting examples of "alkylcarbonyl" include C(0)CH3, C(0)CH2CH2CH3 and C(0)CH(CH3)2.
The term "alkoxycarbonyl" means alkoxy group substituted on the carbonyl group. Non-limiting examples of "alkoxycarbonyl " include CH3OC(=0), CH3CH2OC(=0), CH3CH2CH2OC(=0), (CH3)2CHOC(=0) and the different butoxy or pentoxycarbonyl isomers. The term "alkylaminocarbonyl" means alkylamino substituted on the carbonyl group. Non-limiting examples of "alkylaminocarbonyl" include CH3NHC(=0), CH3CH2NHC(=0), CH3CH2CH2NHC(=0), (CH3)2CHNHC(=0) and the different butylamino or pentylaminocarbonyl isomers.
The term "dialkylaminocarbonyl" means dialkylam ino substituted on the carbonyl group. Non-limiting examples of "dialkylaminocarbonyf'include (CH3)2NC(=0), (CH3CH2)2NC(=0), CH3CH2(CH3)NC(=0), CH3CH2CH2(CH3)NC(=0) and (CH3)2CHN(CH3)C(=0); and the like or different isomers.
Non-limiting examples of "alkoxyalkylcarbonyl" include CH30CH2C(=0), CH3OCH2CH2C(=0), CH3CH2OCH2C(=0), CH3CH2CH2CH2OCH2C(=0) and CH3CH20CH2CH2C(=0) and the like or different isomers. Examples of "alkylthioalkylcarbonyl" include CH3SCH2C(=0), CH3SCH2CH2C(=0), CH3CH2SCH2C(=0), CH3CH2CH2CH2SCH2C(=0) and CH3C112SCH2CH2C(=0) and the like or different isomers. The term "haloalkylsufonylaminocarbonyl", "alkylsulfonylaminocarbonyl", "alkyithioalkoxycarbonyl", "alkoxycarbonylalkylamino" and the like are defined analogously
Non-limiting examples of "alkylaminoalkylcarbonyl" include CH3NHCFi2C(=0), CH3NHCH2CH2C(=0), CH3CH2NHCH2C(=0), CH CH2CH2CH2NHCH2C(=0) and CH3CH2NHCH2CH2C(=0) and the like or different isomers.
The term "amide" means A-R'C(=0)NR"-B, wherein R' and R" indicates substituents and A and B indicate any group.
The term "thioamide" means A-R'C(=S)NR"-B, wherein R' and R" indicates substituents and A and B indicate any group. The total number of carbon atoms in a substituent group is indicated by the "Q to C " prefix wherein i and j are numbers from 1 to 21. For example, CrC3 alky!sulfonyl designates methylsulfonyl through propylsulfonyl; C2 alkoxyalkyl designates CH3OCH2; C3 alkoxyalkyl designates, for example, CH3CH(OCH3), CH3OCH2CH2 or CH3CH2OCH2; and C4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH3CFI2CH2OCH2 and CH3CH2OCH2CH2. In the above recitations, when a compound of Formula I is comprised of one or more heterocyclic rings, all substituents are attached to these rings through any avai lable carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can exceed 1 , said substituents (when they exceed 1 ) are independently selected from the group of defined substituents. Further, when the subscript m in (R)m indicates an integer ranging from for example 0 to 4 then the number of substituents may be selected from the integers between 0 and 4 inclusive.
The groups defined herein above may further be substituted with any of the possible substitutent described herein above. In any of the above recitations, when a compound of Formula I is comprised of one or more heterocyclic rings, the substituents may be attached to these rings through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
In any of the above recitations, the substituents may be optional ly further substituted.
When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can exceed 1 , said substituents (when they exceed 1 ) are independently selected from the group of defined substituents. Further, when the subscript "m" in (R)m indicates an integer ranging from for example 0 to 4 then the number of substituents may be selected from the integers between 0 and 4 i nclusive.
When a group contains a substituent which can be hydrogen, for example R , or R2, then, when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being un-substituted.
The embodiments herein and the various features and advantageous details thereof are explained with reference to the non-limiting embodiments in the description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessari ly obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skilled in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
The description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.
Any discussion of documents, acts, materials, devices, articles and the like that has been included in this specification is solely for the purpose of providing a context for the invention. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the invention as it existed anywhere before the priority date of this application.
The numerical values mentioned in the description and the claims though might form a critical part of the present invention, any deviation from such numerical values shall stil l fall within the scope of the present invention if that deviation fol lows the same scientific principle as that of the present invention. The term "pest" for the purpose of the present invention includes but is not limited to fungi, stramenopiles (oomycetes), bacteria, nematodes, mites, ticks, insects and rodents. The term "plant" is understood here to mean al l plants and plant populations, such as desired and undesired wi ld plants or crop plants (including naturally occurring crop plants). Crop plants may be plants which can be obtained by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or combinations of these methods, including the transgenic plants and including the plant cultivars which are protectable and non-protectable by plant breeders' rights.
For the purpose of the present invention the term "plant" includes a living organism of the kind exemplified by trees, shrubs, herbs, grasses, ferns, and mosses, typically growing in a site, absorbing water and required substances through its roots, and synthesizing nutrients in its leaves by photosynthesis.
Examples of "plant" for the purpose of the present invention include but are not limited to agricultural crops such as wheat, rye, barley, triticale, oats or rice; beet, e.g. sugar beet or fodder beet; fruits, such as pomes, stone fruits or soft fruits, e.g. apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries, blackberries or gooseberries; leguminous plants, such as lentils, peas, alfalfa or soybeans; oil plants, such as rape, mustard, olives, sunflowers, coconut, cocoa beans, castor oil plants, oil palms, ground nuts or soybeans; cucurbits, such as squashes, cucumber or melons; fiber plants, such as cotton, flax, hemp or j ute; citrus fruit, such as oranges, lemons, grapefruits or mandarins; vegetables, such as spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, cucurbits or paprika; lauraceous plants, such as avocados, cinnamon or camphor; energy and raw material plants, such as corn, soybean, rape, sugar cane or oil palm; corn; tobacco; nuts; coffee; tea; bananas; vines (table grapes and grape juice grape vines); hop; turf; sweet leaf (also called Stevia); natural rubber plants or ornamental and forestry plants, such as flowers, shrubs, broad-leaved trees or evergreens, e.g. conifers; and on the plant propagation material, such as seeds, and the crop material of these plants. Preferably, the plant for the purpose of the present invention include but is not limited to cereals, corn, rice, soybean and other leguminous plants, fruits and fruit trees, grapes, nuts and nut trees, citrus and citrus trees, any horticultural plants, cucurbitaceae, oleaginous plants, tobacco, coffee, tea, cacao, sugar beet, sugar cane, cotton, potato, tomato, onions, peppers and vegetables, ornamentals, any floricultural plants and other plants for use of human and animals.
The term "plant parts" is understood to mean all parts and organs of plants above and below the ground. For the purpose of the present invention the term plant parts includes but is not limited to cuttings, leaves, twigs, tubers, flowers, seeds, branches, roots including taproots, lateral roots, root hairs, root apex, root cap, rhizomes, slips, shoots, fruits, fruit bodies, bark, stem, buds, auxil iary buds, meristems, nodes and internodes. The term "locus thereof includes soil, surroundings of plant or plant parts and equipment or tools used before, during or after sowing/planting a plant or a plant part.
Appl ication of a compound or compounds of the present invention or the compound of the present invention in a composition optionally comprising at-least one other active compatible compound to a plant or a plant material or locus thereof include application by a technique known to a person skilled in the art which include but is not limited to spraying, coating, dipping, fumigating, impregnating, injecting and dusting.
The term "applied" means adhered to a plant or plant part either physically or chemically.
The invention disclosed in the present invention shall now be elaborated with the help of non-limiting schemes and examples.
The present invention relates to a compound selected from Formula I,
Figure imgf000016_0001
The present invention is inclusive of salts, metal complexes, N-oxides, isomers, and polymorphs of compound of Formula I, wherein
E is a fragment selected from the group consisting of E- 1 to E-5:
Figure imgf000016_0002
E- 1 E-2 E-3 E-4 E-5
In one embodiment E is E-1 . T1, T2 T"' and T4 are independently selected from 5- or 6- membered aryl ring or 5- or 6-membered saturated or partially saturated cyclic ring or 5- or 6- membered heteroaryl ring or 5- or 6-membered saturated or partially saturated heterocyclic ring, wherein each ring member of heteroaryl ring is selected from C, N, O and S, and wherein each ring member of heterocyclic ring is selected from C, N, O, S(0).„ C(=0), C(=S), S(=NR2) and S(0)=NR2, and T1, T2 , T3 and T4 are optionally substituted by one or more R1 on C atoms and one or more R2 on hetero atoms.
In one embodiment T' is independently selected from 5- or 6- membered heteroaryl ring or 5- or 6- membered saturated or partially saturated heterocyclic ring, wherein each ring member of heteroaryl ring is selected from C, N, O and S, and wherein each ring member of heterocyclic ring is selected from C, N, O, S(0)a, C(=0), C(=S), S(=NR2) and S(0)=NR2, and T1 is optionally substituted by one or more R1 on C atoms and one or more R2 on hetero atoms.
In another embodiment T1 is independently selected from 5- or 6- membered heteroaryl ring or 5- or 6- membered saturated or partially saturated heterocyclic ring, wherein each ring member of heteroaryl ring is selected from C, N, O and S, and wherein each ring member of heterocyclic ring is selected from C, N, O, S(0)a, C(=0), and C(=S), and T1 is optionally substituted by one or more R1 on C atoms and one or more R2 on hetero atoms.
Non-limiting representative examples of T1 are depicted herein below.
Figure imgf000017_0001
T1 T2 T3 T4 T5 T6 T7 T8 T9
Figure imgf000017_0002
T10 T11 T12 T13 T14 T15 T16 T17 T18
Figure imgf000017_0003
T19 T20 T21 T22 T23 T24 T25 T26 T27
Figure imgf000017_0004
T28 T29 T30 T31 T32 T33 T34 T35 T36 
Figure imgf000018_0001
Figure imgf000019_0001
T92 T93 T94 T95 T96 T97 T98
Figure imgf000019_0002
T107 T108 T109 T110 T111 T112
Figure imgf000019_0003
T113 T114 T115 T116 T117 T118 T119
Figure imgf000019_0004
T128 T129 T130 T131 T132 T133 T134 T135
Figure imgf000019_0005
Figure imgf000020_0001
T164 T165 T166 T167
Alternatively, T2 ? T3 and T4 are independently selected from C rC6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C r C6 haloalkyl, C2-Q, haloalkenyl, C2-C6 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C rC6 alkyl C3-C8 cycloalkyl, C3-C8 cycloalkyl CrC6 alkyl, C3-C8 cycloalkyl C3-C8 cycloalkyl, C3-C8 halocycloalkyl C|-C6 alkyl, C|-C6 alkoxy C,-C6 alkyl, C3-C6 cycloalkoxy C rC6 alkyl, C C6 alkylthio C rC6 alkyl, CrC6 alkylsulfinyl C C6 alkyl, CrC6 alkylsulfonyl C rC6 alkyl, C C6 alkylamino CrC6 alkyl, CrC6 dialkylamino CrC6 alkyl, CrC6 haloalkylamino C C6 alkyl, C3-C8 cycloalkylamino CrC6 alkyl, C,-C6 alkylcarbonyl, CrC6 haloalkylcarbonyl, C3-C8 cycloalkylcarbonyl, C C6 alkoxycarbonyl, C3-C8 cycloalkoxycarbonyl, CrC6 alkylaminocarbonyl, C rCb dialkylaminocarbonyl, C3-C8 cycloalkylaminocarbonyl, C rC6 haloalkoxy C rC6 alkyl, C,-C6 hydroxyalkyl, CrC6 alkoxy, CrC6 haloalkoxy, C3-C8 cycloalkoxy, C3-C8 halocycloalkoxy, C3-C8 cycloalkyl Ci -C6 alkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C rC6 alkoxy C rC6 alkoxy, CrC6 alkylcarbonyloxy, CrC6 haloalkylcarbonyloxy, C3-C8 cycloalkylcarbonyloxy, CrC6 alkylcarbonyl CrC6 alkoxy, C rC6 alkylthio, C rC6 haloalkylthio, C3-C8 cycloalkylthio, C C6 alkylsulfinyl, CrC6 haloalkylsulfinyl, C!-C6 alkylsulfonyl, C rC6 haloalkylsulfony!, C3-C8 cycloalkylsulfonyl, CrC6 trialkylsilyl, C rC6 alkylsulfonylamino, and C rC6 haloalkylsulfonylamino.
In one embodiment A is a direct bond or C(R4)2 or C(R4) C(R4)2, C(=0) or NR5.
In another embodiment A is C(R4)2 or NR5.
In one embodiment Z is C or N. In one of the preferred embodiments Z is C. In one embodiment the substitutent R3 is selected from hydrogen, halogen, cyano, hydroxy, amino, aldehyde, carboxylic acid, C rC6 alkyl, C2-C5 alkenyl, C2-C6 alkynyl, C ,-C6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyi, C C6 alkyl C -C6 cycloalkyl, C:,-C6 cycloalkyl C C6 alkyl, C3-C6 halocycloalkyi C |-C6 alkyl, C3-C6 cycloalkenyl, C3-C6 halocycloalkenyl, C C6 alkoxy CrC6 alkyl, C C6 alkyl C rC6 thioalkyl, C rC6 alkyl CrC6 sulfinylalkyl, CrC6 alkyl CrC6 sulfonylalkyl, CrC6 alkylamino C rC6 alkyl, CrC6 dialkylamino C, -C6 alkyl, C rC6 haloalkylamino C C6 alkyl, C rC6 alkylcarbonyl, C ,-C6 haloalkylcarbonyl, C3-C6 cycloaikylcarbonyl, C rC6 alkoxycarbonyl, C3-C6 cycloalkoxycarbonyl, C3-C6 cycloalkyl C rC6 alkoxycarbonyl, C i-C6 alkylaminocarbonyl, C|-C6 dialkylaminocarbonyl, C C6 alkoxy, C |-C6 haloalkoxy, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-Cb alkynyloxy, C2-C6 haloalkynyloxy, C ,-C6 alkoxy C)-C6 alkoxy, C rC6 alkylcarbonyloxy, C rC6 haloalkylcarbonyloxy, Ci-C6 alkylthio, CrC6 haloalkylthio, C3-C6 cycloa!kylthio,
Figure imgf000021_0001
alkylamino, C rC6 dialkylamino, C C6 haloalkylamino, C C6 halodialkylamino, C3-C6 cycloalkylamino, CrC6 alkylcarbonylamino, C]-C6 haloalkylcarbonylamino, CrC6 alkylsulfonylamino and C i-C6 haloalkylsulfonylamino. In another embodiment, two R3 are taken together as C C6 alkyl, C,-C4 alkylene or C2-C4 alkenylene to form a bridged bicyclic or fused bicyclic ring system.
In yet another embodiment, two R3 attached to adjacent ring carbon atoms are taken together as -CH=CH- CH=CH- optionally substituted with a substituent selected from CrC4 alkyl, C C4 haloalkyl, CrC4 alkoxy, CrC4 haloalkoxy, halogen, hydroxy, amino, cyano and nitro. In one of the preferred embodiments R3 is selected from hydrogen, CrC4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, CrC4 haloalkyl, C,-C4 alkoxy, halogen, cyano and hydroxy.
G is an optionally substituted 5- or 6- membered heteroaryl ring or 5- or 6-membered saturated or partially saturated heterocyclic ring, each ring member is selected from C, N, O, S(=0)a, C(=0), C(=S), S(=NR2) and S(=0)=NR2. In one of the preferred embodiments G is selected from optionally substituted G l to G63, each substituent selected from R3a on carbon ring members and Rl la on nitrogen ring members.
G l to G63 are as depicted herein below:
Figure imgf000022_0001
G1 G2 G3 G4 G5 G6 G7
Figure imgf000022_0002
G8 G9 G10 G11 G12 G13 G14
Figure imgf000022_0003
G15 G16 G17 G18 G19 G20 G21
Figure imgf000022_0004
G29 G30 G31 G32 G33 G34 G35
Figure imgf000022_0005
G43 G44 G45 G46 G47 G48 G49
Figure imgf000023_0001
G50 G51 G52 G53 G54 G55 G56
Figure imgf000023_0002
G57 G58 G59 G61 G62 G63 wherein the bond indicated by ^~ is attached to ring D and the bond indicated by ~ is attached to J. R3a and Rl la may be attached to one or more possible position/s.
The substituent R3a is hydrogen or R3b. The substituent R3b is a phenyl or 5- or 6-membered heteroaryl ring optionally substituted with one or more substituents independently selected from R4a on carbon ring members and R b on nitrogen ring members. Alternatively, R31' is independently C C3 alkyl, C r C3 haloalkyi or halogen.
The substituent R',a is independently selected from C rC6 alkyl, C2-Q, alkenyl, C2-C6 alkynyl, C3- C6 cycloalkyl, C3-C6 cycloalkyl C rC6 alkyl, C rC6 alkyl C3-C6 cycloalkyl, C ,-C6 haloalkyi C3-C6 cycloalkyl, CrC6 haloalkyi, C2-C6 haloaikenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl, halogen, hydroxy, amino, cyano, nitro, C rC6 alkoxy, CrC6 haloalkoxy, C rC6 alkylthio, CrC6 alkylsulfinyl, Cr C6 alkylsulfonyl, C rC6 haloalkylthio, CrC6 haloalkylsulfinyl, C ,-C6 haloalkyisulfonyl, CrC6 alkylamino, CrC6 dialkylamino, C3-C6 cycloalkylamino, C|-C6 alkoxy C )-C6 alkyl, C rC6 hydroxyalkyl, C r C6 alkylcarbonyl, C C6 alkoxycarbonyl, C ,-C6 alkylcarbonyloxy, C rC6 alkylcarbonylthio, C r C6 alkylaminocarbonyl, C C6 dialkylaminocarbonyl and C C6 trialkylsilyl .
The substituent R4b is independently selected from C rCb alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3- C6 cycloalkyl, Ci-C6 haloalkyi, C2-C6 haloaikenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl and Cj-C6 alkoxy C C6 alkyl.
The substituent Rl i a is hydrogen or R l lb and the substituent R i l b is independently C C3 alkyl, C2- Cc alkenyl, C2-C alkynyl, C3-C6 cycloalkyl, C C6 haloalkyi, C2-C6 haloaikenyl, C2-C6 haloalkynyl, C3- C6 halocycloalkyl and C rC6 alkoxy C|-C6 alkyl. J is selected from fragments of Formula II & III
Figure imgf000024_0001
11 III
The right side of the fragment of Formula II or III is attached to Q and the left side of the fragment of Formula II or III is attached to G. L6 and L7 are independently a direct bond, O, C(=0), C(=S), C(R,2)2, C(Rl2) C(Rl2)2> NR13 or NRl3C(=0).
In another embodiment, L6 and L7 together with the atoms to which they are attached may form a 4- to 7- membered carbocycl ic or heterocycl ic ring or ring system.
The substituent Rn together with L6 or L7 or G or Q or R 12 or R13 or R14 or R15 may form a 4- to 7- membered carbocyclic or heterocyclic ring or ring system.
"m" is an integer 0 to 1 ;
In one embodiment, Q is independently phenyl, benzyl, naphthalenyl, a 5- or 6- membered aryl ring, an 8- to 1 1 - membered aryl multi-cyclic ring system, an 8- to 1 1 - membered aryl fused ring system, a 5- or 6- membered heteroaryl ring, an 8- to 1 1 - membered heteroaryl multi-cyclic ring system or an 8- to 1 1 - membered heteroaryl fused ring system, each ring member of the ring or the ring system is selected from C, N, O and S, and each ring or ring system is optionally substituted with R14 on carbon atoms and R 15 on hetero atoms.
In another embodiment, Q is independently a 3- to 7- membered nonaromatic carbocyclic ring, a 5-, 6- or 7- membered nonaromatic heterocyclic ring, an 8- to 1 5- membered nonaromatic multi-cyclic ring system or an 8- to 1 5- membered nonaromatic fused ring system, each ring member of the ring or the ring system is selected from C, N, O, S(0)B, C(=0), C(=S), S(=NR2) and S(= )=NR2 & SiR16R 17, and each ring or ring system is optionally substituted with R 14 on carbon atoms and R 15 on hetero atoms.
In one of the preferred embodiments, Q is selected from Q l to Q99 and the presentation " " is a single or a double bond. The substituent R 14 may be attached to one or more position/s. 
Figure imgf000025_0001

Figure imgf000026_0001
W'isOR18, SR19, N(R20)2orR21.
The substituents R1, R2, R6, R7, R8, R9, Ri0, R14, R15, R18, R19, R20, R2', R2" and R27 are independently selected from hydrogen, halogen, hydroxy, cyano, nitro, CrC6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C C6 haloalkyl, C2-C<, haioalkenyl, C2-C6 haloa!kynyl, C3-C8 cycloalkyl, C3-C8 halocycloaikyl, Ci-C6 alkyl C3-C8 cycloalkyl, C -C8 cycloalkyl CrC6 alkyl, C3-C8 cycloalkyl C3-C8 cycloalkyl, C3-C8 halocycloaikyl C,-C6 alkyl, C C6 alkoxy CrC6 alkyl, C3-C8 cycloalkoxy CrC6 alkyl, C|-C6 alkylthio C|-C() alkyl, C Cb alkylsulfinyl CrC6 alkyl, CrC6 alkylsulfonyl CrC6 alkyl, CrC6 alkylamino, CrC6 dialkyl amino, C,-C6 alkylamino CrC6 alkyl, CrC6 dialkylamino CrC6 alkyl, CrC6 haloalkylamino CrC6 alkyl, C3-C8 cycloalkylamino, C3-C8 cycloalkylamino CrC6 alkyl, C C6 alkylcarbonyl, CrC6haloalkylcarbonyl, C -C8 cycloalkylcarbonyl, Ci-C6 alkoxycarbonyl, C3-C8 cycloalkoxycarbonyl, C|-C6 alkylaminocarbonyl, CrC6 dialkylaminocarbonyl, C3-C8 cycloalkylaminocarbonyl, Ci-C6 haloalkoxy C C6 alkyl, CrC6 hydroxyalkyl, CrC6 hydroxyalkenyl, C,-C6 hydroxyalkynyl, CrC6 alkoxy, CrC6 haloalkoxy, CrC6 cycloalkoxy, C3-C8 halocycloalkoxy, C3-C8 cycloalkyl CrC6 alkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, CrC6 alkoxy CrC6 alkoxy, CrC6 alkylcarbonyloxy, C C6 haloalkylcarbonyloxy, C3-C6 cycloalkylcarbonyloxy, CrC6 alkylcarbonyl C C6 alkoxy, Ci-C6 alkylthio, C]-C6 haloalkylthio, C3-C3 cycloalkylthio, C C6 alkylsulfinyl, CrC6 haloalkylsulfinyl, Ci-C6 alkylsulfonyl, CrC6 haloalkylsulfonyl, C3-C8 cycloalkylsulfonyl, C3-C8 cycloalkylsulfinyl, CrCb trialkylsilyl, C C6 alkylsulfonylamino, C,-C6 haloalkylsulfonylamino, Cj-C6 alkylcarbonylthio, CrC6 alkylsulfonyloxy, C!-C6 alkylsulfinyloxy, arylsulfonyloxy, arylsulfmyloxy, arylsulfonyl, arylsulfinyl, C,-C6 cyanoalkyl, C2-C6 alkenylcarbonyloxy, C,-C6 alkoxy C|-C6 alkylthio, Cr C6 alkylthio C C6 alkoxy, C2-C6 haloalkenylcarbonyloxy, C C6 alkoxy C2-C6 alkynyl, C2-C6 alkynylthio, C3-C8 halocycloalkylcarbonyloxy, C2-C6 alkenylamino, C2-C6 alkynylamino, CrC6 haloalkylamino, C3-C8 cycloalkyl C Cfl alkylamino, CrC6 alkoxyamino, CrC6 haloalkoxyamino, CrC6 alkylcarbonylamino, Cr C(, haloalkylcarbonylamino, C|-C6 alkoxycarbonyl ami no, C2-C6 alkenylthio, C C6 haloalkoxycarbonyl, Ci-C6 alkoxy C]-C6 alkylcarbonyl, C C6 haloalkoxycarbonylamino, C,-C6 alkoxy C C6 alkylaminocarbonyl, C C6 alkylthiocarbonyl, C3-C8 cycloalkenyloxy CrC6 alkyl, CrCb alkoxy CrC6 alkoxycarbonyl, C C6 haloalkoxy CrC6 haloalkoxy, CrCc alkoxy CrC6 haloalkoxy, C3-C8 halocycloalkoxy C C6 alkyl, C C6 dialkylaminocarbonylamino, C,-C6 alkoxy C2-C6 alkenyl, CrC6 alkylthiocarbonyloxy, C]-C(, haloalkoxy CrC6 alkoxy, C|-C6 haloalkylsulfonyloxy, CrC6 alkoxy C C6 haloalkyl, CrC6 dihaloalkylamino, CrC6 dialkoxy CrC6 alkyl, CrC6 alkylaminocarbonylamino, CrC6 haloalkoxy CrC6 haloalkyl, C,-C6 alkylaminocarbonyl C C6 alkylamino, CrC6 trialkylsilyl C2-C6 alkynyloxy, CrC6trialkylsilyloxy, C C(, trialkylsilyl C2-C6 alkynyl, CrC6 cyanoalkoxy C,-C6 alkyl, C C6 dialkylthio CrC6 alkyl, CrC6 alkoxysulfonyl, C3-C8 halocycloalkoxycarbonyl, CrC6 alkylcy C3-C8 cloalkylcarbonyl, C3-C8 halocyclo C C6 alkylcarbony!, C2-C6 alkenyloxycarbonyl, C2-C6 alkynyloxycarbonyl, C|-C(, cyanoalkoxycarbonyl, CrC6 alkylthio CrC(, alkoxycarbonyl, C2-C6 alkynylcarbonyloxy, C2-C6 haloalkynylcarbonyloxy, cyanocarbonyloxy, CrC6 cyanoalkylcarbonyloxy, C3-C8 cycloalkylsulphonyloxy, C3-C8 cycloalkyl CrC6 alkylsulphonyloxy, C -C8 halocycloalkylsulphonyloxy, C2-C6 alkenylsulphonyloxy, C2-C6 alkynylsulphonyloxy, C C6 cyanoalkylsulphonyloxy, C2-C6 haloalkenylsulphonyloxy, C2-C6 haloalkynylsulphonyloxy, C2-C6 alkynylcycloalkyloxy, C2-C6 cyanoalkenyloxy, C2-Q cyanoalkynyloxy, C,-C6 alkoxycarbony!oxy, C2-C6 alkenyloxycarbonyloxy, C2-C6 alkynyloxycarbonyloxy, C C6 alkoxyalkylcarbonyloxy, sulfilimines, sulfoximines, SF5 or -L8Q. The substituents R9 and R10 of E-5 taken together with the atoms to which they are attached form a saturated, unsaturated or partially unsaturated 4- to 7- membered carbocyclic or heterocyclic ring or ring system, each ring member is selected from C, N, O, S(=0)a, C(=0), C(=S), S(=NR2) and S(0)=NR2, and said ring optionally substituted by R24 on carbon atoms and R27 on hetero atoms.
R16 and R17 are independently selected from CrC6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkyl C C6 alkyl, CrC6 alkyl C3-C6 cycloalkyl, C,-C6 haloalkyl C3-C6 cycloalkyl, CrC6 haloalkyl, CrC6alkoxy and CrC6 haloalkoxy.
W is O or S. Preferably W is O.
L', L2 fL3 ,L\L5, and L8 are independently a direct bond, O, S(=0)„ C(=0), C(=S), C(R22)2, C(R22)2- C(R2 )2,or NR23. In one of the preferred embodiments, L1 is a direct bond or O or S or NR23.
The substituents R4, R12, and R22 are independently selected from hydrogen, halogen, cyano, hydroxy, aldehyde, C,-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C,-C6 haloalkyl, C -C6 haloalkenyl, C2- C6 haloalkynyl, CrC6alkoxy CrC6 alkyl, CrC6 alkylthio CrC6 alkyl, CrC6 alkylsulfinyl C C6 alkyl, C,- C alkylsulfonyl C -Cb alkyl, CrC6 alkylcarbonyl, CrC6 haloalkylcarbonyl, C|-C6 alkoxycarbonyl, Cr Cf, alkoxycarbonyl CrC6 alkyl, CrC6 alkylaminocarbonyl, CrC6 dialkylaminocarbonyl, C|-C6alkoxy, C|-C6 haloalkoxy, C C6 alkylthio, C,-C6 haloalkylthio, CrC6 alkylsulfinyl, CrC6 haloalkylsulfinyl, Cr C6 alkylsulfonyl and CrC6 haloalkylsulfonyl.
The substituents R5, R13, and R23 are independently selected from hydrogen, CrC6 alkyl, C?-C(, alkenyl, C2-C6 alkynyl, CrC6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, CrC6alkoxy C|-C6 alkyl, C C4 alkylthio C,-C6 alkyl, C,-C6 alkylsulfinyl CrC6 alkyl, CrC6 alkylsulfonyl CrC6 alkyl, C C6 alkylcarbony], C ,-C6 haloalkylcarbonyl, C C6 alkoxycarbonyl , C C6 alkoxycarbonyl C rC6 alkyl, C r C6 alkylaminocarbonyl, C C6 dialkylaminocarbonyl, C,-C6 alkylsulfonyl and C |-C6 haloaikylsulfonyl .
The presentation " " in ring D is a single bond when Z is N. Further, the presentation " " in ring D is a single or double bond when Z is C. In one of the preferred embodiment, the presentation " " is a single bond.
"n" is an integer ranging from 0 to 9 with a proviso that when Z is N, "n" is an integer ranging from 0 to
8; and when the presentation " " in ring D is a double bond then "n" is an integer ranging from 0 to
7. a is independently 0, 1 or 2. The novel and inventive compounds of the present invention, the salts, isomers, metal complexes, N- oxides and polymorphs thereof are effective in preventing against and controlling phytopathogenic microorganisms.
An anion part of the salt in case the compound of Formula I is cationic or capable of forming a cation can be inorganic or organic. Alterntively, a cation part of the salt in case the compound of Formula I is anionic or capable of forming an anion can be inorganic or organic.
Examples of inorganic anion part of the salt include but are not limited to chloride, bromide, iodide, fluoride, sulphate, phosphate, nitrate, nitrite, hydrogen carbonates and hydrogen sulphate.
Examples of organic anion part of the salt include but are not l imited to formate, alkanoates, carbonates, acetates, trifluoroacetate, trichloroacetate, propionate, glycolate, thiocyanate, lactate, succinate, malate, citrates, benzoates, cinnamates, oxalates, alkylsulphates, alkylsulphonates, arylsulphonates aryldisulphonates, alkylphosphonates, arylphosphonates, aryldiphosphonates, p-toluenesulphonate, and salicylate. ;
Examples of inorganic cation part of the salt include but are not limited to alkal i and alkaline earth metals. Examples of organic cation part of the salt include but are not limited to pyridine, methyl amine, imidazole, benzimidazole, histidine, phosphazene, tetramethyl ammonium, tetrabutyl ammonium, choline and trimethyl amine. Metal ions in metal complexes of the compound of Formula I are especially the ions of the elements of the second main group, especially calcium and magnesium, of the third and fourth main group, especially aluminium, tin and lead, and also of the first to eighth transition groups, especially chromium, manganese, iron, cobalt, nickel, copper, zinc and others. Particular preference is given to the metal ions of the elements of the fourth period and the first to eighth transition groups. Here, the metals can be present in the various valencies that they can assume.
Compounds of the present invention may exist in more than one form, and thus include all crystalline and non-crystalline forms of the compounds they represent. Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts. Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types). The term "polymorph" refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice. Although polymorphs can have the same chemical composition, they can also differ in composition due the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability. One skilled in the art will appreciate that a polymorph of a compound of the present invention can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound of the present invention. Preparation and isolation of a particular polymorph of a compound of the present invention can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures. The present invention further relates to a process for preparing the compound of Formula I. The process comprises a step of reacting JQ- 1 with a compound of Formula 5 to obtain a compound of Formula 4. The compound of Formula 4 upon deprotecting provides a compound of Formula 2 which is reacted with E- 1 A to obtain the compound of Formula I;
Figure imgf000030_0001
wherein, R28 is -C(=0)OH, -C(=0)C1, -C(=0)N3> -CH2OH or -CH2X; wherein X is CI, Br or I; L6, R ", G, Q, T 1 and W have the same meaning as described herein before.
In one embodiment the process for preparing the compound of Formula I is as shown hereinbelow:
Figure imgf000031_0001
wherein, W is O or S; R", G, Q and T1 are as defined herein above. In another embodiment the process for preparing the compound of Formula I is as shown hereinbelow:
Figure imgf000031_0002
wherein, W is O or S; R", G, Q and T1 are as defined herein above.
In yet another embodiment the process for preparing the compound of Formula I is as shown herein below:
Figure imgf000031_0003
wherein, W is O or S; R 1 1, G, Q and T1 are as defined herein above.
The present invention also relates to the following intermediates 4 and 2 which are useful in the synthesis of the compound of Formula 1 :
Figure imgf000031_0004
wherein, R " , G, L6, and Q are as defined herein above. The present invention also relates a composition comprising the compound of Formula 1 and one or more excipient.
The compound of Formula I of the present invention in the composition can be an agriculturally acceptable salt, metal complex, constitutional isomer, stereo-isomer, diastereoisomer, enantiomer, chiral isomer, atropisomer, conformer, rotamer, tautomer, optical isomer, geometric isomer, polymorph, or N- oxide thereof.
The excipient may be an inert carrier or any other essential ingredient such as surfactants, additives, solid diluents and liquid diluents.
The composition of the present invention may additionally comprise at least one active compatible compound selected from fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilisers and nutrients. The compounds used in the composition and in combination with the compound of Formula I are also termed as active compatible compounds.
The concentration of the compound of Formula I in the composition of the present invention ranges from 1 to 90% by weight with respect to the total weight of the composition, preferably from 5 to 50% by weight with respect to the total weight of the composition.
The known and reported active compounds such as fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics and nutrients can be combined with at least one compound of Formula I of the present invention. For example, fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilizers and nutrients disclosed and reported in WO201776739 (A to O) can be combined with compound of Formula I of the present invention. The present invention also relates to such combinations comprising the compound of the present invention and active compatible compounds reported in WO201776739.
The fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilizers and nutrients reported in WO201776739, are not reproduced herein for the sake of brevity and are incorporated herein by way of reference as non-limiting examples to be combined with at least one compound of Formula I of the present invention.
The present invention also relates to a use of the compound of Formula 1 or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I for controlling or preventing phytopathogenic micro-organisms such as fungi, stramenopiles, bacteria, insects, nematodes, trematodes, and mites in agricultural crops and or horticultural crops. Particularly, the present invention also relates to a use of the compound of Formula I or the combination or the composition for control ling or preventing phytopathogenic micro-organisms in agricultural crops and or horticulture crops.
The compound of Formula I or the combination or the composition of the present invention may be used to treat several fungal pathogens. Non-limiting examples of pathogens of fungal diseases which can be treated in accordance with the invention include:
Diseases caused by pathogens from the group of the Stramenopiles, particularly by Oomycetes, for example Albugo species, for example Albugo Candida; Bremia species, for example Bremia lactucae; Peronospora species, for example Peronospora pisi or P. brassicae; Phytophthora species, for example Phytophthora infestans; Plasmopara species, for example Plasmopara viticola; Pseudoperonospora species, for example Pseudoperonospora humuli or Pseudoperonospora cubensis; Pythium species, for example Pythium ultimum;
Diseases caused by powdery mildew pathogens, for example Blumeria species, for example Blumeria graminis; Podosphaera species, for example Podosphaera leucotricha; Sphaerotheca species, for example Sphaerotheca fuliginea; Uncinula species, for example Uncinula necator; Erysiphe species, for example Erysiphe cichoracearu;
Diseases caused by rust disease pathogens, for example Gymnosporangium species, for example Gymnosporangium sabinae; Hemileia species, for example Hemileia vastatrix; Phakopsora species, for example Phakopsora pachyrhizi or Phakopsora meibomiae; Puccinia species, for example Puccinia recondita, Puccinia graminis oder Puccinia striiformis; Uromyces species, for example Uromyces appendiculatus;
Leaf blotch diseases and leaf wilt diseases caused, for example, by Alternaria species, for example Alternaria solani; Cercospora species, for example Cercospora beticola; Cladiosporium species, for example Cladiosporium cucumerinum; Cochliobolus species, for example Cochliobolus sativus (conidial form: Drechslera, syn: Helminthosporium) or Cochliobolus miyabeanus; Colletotrichum species, for example Colletotrichum lindemuthanium; Cycloconium species, for example Cycloconium oleaginum; Diaporthe species, for example Diaporthe citri; Elsinoe species, for example Elsinoe fawcettii; Gloeosporium species, for example Gloeosporium laeticolor; Glomerella species, for example Glomerella cingulata; Guignardia species, for examplge Guignardia bidwelli; Leptosphaeria species, for example Leptosphaeria maculans; Magnaporthe species, for example Magnaporthe grisea; Microdochium species, for example Microdochium nivale; Mycosphaerella species, for example Mycosphaerella graminicola, Mycosphaerella arachidicola or Mycosphaerella fijiensis; Phaeosphaeria species, for example Phaeosphaeria nodorum; Pyrenophora species, for example Pyrenophora teres or Pyrenophora tritici repentis; Ramularia species, for example Ramularia collo-cygni or Ramularia areola; Rhynchosporium species, for example Rhynchosporium secalis; Seploria species, for example Sepioria apii or Septoria lycopersici; Stagonospora species, for example Stagonospora nodorum; Typhula species, for example Typhula incarnaia; Venturia species, for example Venturia inaequalis;
Root and stem diseases caused, for example, by Corticium species, for example Corticium gramineanim; Fusarium species, for example Fusarium oxysporum; Gaeumannomyces species, for example Gae mannomyces gi'aminis; Plasmodiophora species, for example Plasmodiophora brassicae; Rhizoctonia species, for example Rhizoctonia solani; Sarocladium species, for example Sarocladium oryzae; Sclerotium species, for example Sclerotium oryzae; Tapesia species, for example Tapesia acuformis; Thielaviopsis species, for example Thielaviopsis basicola; Ganoderma species, for example Ganoderma lucidiim;
Ear and panicle diseases (including corn cobs) caused, for example, by Alternaria species, for example Alternaria spp.; Aspergillus species, for example Aspergillus flavus; Cladosporium species, for example Cladosporium cladosporioides; Claviceps species, for example Claviceps purpurea; Fusarium species, for example Fusarium culmorum; Gibberella species, for example Gibberella zeae; Monographella species, for example Monographella nivalis; Stagnospora species, for example Stagnospora nodorum;
Diseases caused by smut fungi, for example Sphacelotheca species, for example Sphacelotheca reiliana; Tilletia species, for example Tilletia caries or Tilletia controversa; Urocystis species, for example Urocystis occulta; Ustilago species, for example Ustilago nuda;
Fruit rot caused, for example, by Aspergillus species, for example Aspergillus flavus; Botrylis species, for example Botrytis cinerea; Penicillium species, for example Penicillium expansum or Penicillium purpurogenum; Rhizopus species, for example Rhizopus stolonifer; Sclerotinia species, for example Sclerotinia sclerotiorum; Verticilium species, for example Verticilium alboatrum;
Seed- and soil-borne rot and wilt diseases, and also diseases of seedlings, caused, for example, by Alternaria species, for example Alternaria brassicicola; Aphanomyces species, for example Aphanomyces euteiches; Ascochyta species, for example Ascochyta lentis; Aspergillus species, for example Aspergillus flavus; Cladosporium species, for example Cladosporium herbarum; Cochliobolus species, for example Cochliobolus sativus (conidial form: Drechs!era, Bipolaris Syn: Helminthosporium); Colletotrichiim species, for example Colletotrichiim coccodes; Fusarium species, for example Fusarium culmorum; Gibberella species, for example Gibberella zeae; Macrophomirta species, for example Macrophomina phaseolina; Microdochium species, for example Microdochium nivale; Monographella species, for example Monographella nivalis; Penicillium species, for example Penicillium expansum; Phoma species, for example Phoma lingam; Phomopsis species, for example Phomopsis sojae; Phytophthora species, for example Phytophthora cactorum; Pyrenophora species, for example Pyrenophora graminea; Pyricularia species, for example Pyricularia oryzae; Pythium species, for example Pythium ultimum; Rhizoctonia species, for example Rhizoctonia solani; Rhizopus species, for example Rhizopus oryzae; Sclerotium species, for example Sclerotium rolfsii; Septoria species, for example Septoria nodorum; Typhula species, for example Typhula incarnata; Verticillium species, for example Verticillium dahliae; Cancers, galls and witches' broom caused, for example, by Nectria species, for example Nectria galligena;
Wilt diseases caused, for example, by Monilinia species, for example Monilinia laxa;
Deformations of leaves, flowers and fruits caused, for example, by Exobasidium species, for example Exobasidium vexans; Taphrina species, for example Taphrina deformans; Degenerative diseases in woody plants, caused, for example, by Esca species, for example Phaeomoniella chlamydospora, Phaeoacremonium aleophilum or Fomitiporia mediterranea; Ganoderma species, for example Ganoderma boninense;
Diseases of flowers and seeds caused, for example, by Botrytis species, for example Botrytis cinerea;
Diseases of plant tubers caused, for example, by Rhizoctonia species, for example Rhizoctonia solani; Helminthosporium species, for example Helminthosporium solani;
Diseases caused by bacterial pathogens, for example Xanthomonas species, for example Xanthomonas campestris pv. oryzae; Pseudomonas species, for example Pseudomonas syringae pv. lachrymans; Erwinia species, for example Erwinia amylovora; Ralstonia species, for example Ralstonia solanacearum; Fungal diseases on roots and the stem base caused, for example, by black root rot (Calonectria crotalariae), charcoal rot {Macrophomina phaseolina), fusarium blight or wilt, root rot, and pod and collar rot (Fusarium oxysporum, Fusarium orthoceras, Fusarium semitectum, Fusarium ecjuiseti), mycoleptodiscus root rot (Mycoleptodiscus terreslris), neocosmospora (Neocosmospora vasinfectd), pod and stem blight (Diaporthe phaseolorum), stem canker (Diaporthe phaseolorum var. caiilivora), phytophthora rot (Phytophthora megasperma), brown stem rot (Phialophora gregata), pythium rot {Pylhiitm aphanidermatum, Pythium irregulare, Pythium debaryamtm, Pythium myriotylum, Pythium ultimum), rhizoctonia root rot, stem decay, and damping-off {Rhizoctonia solani), sclerotica stem decay {Sclerotinia sclerotiorum), sclerotinia southern blight {Sclerotinia rolfsii), thielaviopsis root rot {Thielaviopsis basicola). Plants which can be treated in accordance with the invention include the following: Rosaceae sp (for example pome fruits such as apples, pears, apricots, cherries, almonds and peaches), Ribesioidae sp., Juglandaceae sp., Betulaceae sp., Anacardiaceae sp., Fagaceae sp. , Moraceae sp. , Oleaceae sp. , Actinidaceae sp. , Lauraceae sp. , Musaceae sp. (for example banana trees and plantations), Rubiaceae sp. (for example coffee), Theaceae sp. , Sterculiceae sp., Rutaceae sp. (for example lemons, oranges and grapefruit); Vitaceae sp. (for example grapes); Solanaceae sp. (for example tomatoes, peppers), Liliaceae sp., Asteraceae sp. (for example lettuce), Umbelliferae sp., Cruciferae sp. , Chenopodiaceae sp. , Cucurbitaceae sp. (for example cucumber), Alliaceae sp. (for example leek, onion), Papilionaceae sp. (for example peas); major crop plants, such as PoaceaelGramineae sp. (for example maize, turf, cereals such as wheat, rye, rice, barley, oats, millet and triticale), Asteraceae sp. (for example sunflower), Brassicaceae sp. (for example white cabbage, red cabbage, broccoli, cauliflower, Brussels sprouts, pak choi, kohlrabi, radishes, and oilseed rape, mustard, horseradish and cress), Fabacae sp. (for example bean, peanuts), Papilionaceae sp. (for example soya bean), Solanaceae sp. (for example potatoes), Chenopodiaceae sp. (for example sugar beet, fodder beet, swiss chard, beetroot); Malvaceae (for example cotton); useful plants and ornamental plants for gardens and wooded areas; and genetically modified varieties of each of these plants.
The agricultural or horticulture crops are wheat, rye, barley, triticale, oats or rice; beet, e.g. sugar beet or fodder beet; fruits, such as pomes, stone fruits or soft fruits, e.g. apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries, blackberries or gooseberries; leguminous plants, such as lentils, peas, alfalfa or soybeans; oil plants, such as rape, mustard, olives, sunflowers, coconut, cocoa beans, castor oil plants, oil palms, ground nuts or soybeans; cucurbits, such as squashes, cucumber or melons; fiber plants, such as cotton, flax, hemp or jute; citrus fruit, such as oranges, lemons, grapefruits or mandarins; vegetables, such as spinach, lettuce, asparagus, cabbages; carrots, onions, tomatoes, potatoes, cucurbits or paprika; lauraceous plants, such as avocados, cinnamon or camphor; energy and raw material plants, such as corn, soybean, rape, sugar cane or oil palm; corn; tobacco; nuts; coffee; tea; bananas; vines (table grapes and grape juice grape vines); hop; turf; sweet leaf (also called Stevia); natural rubber plants or ornamental and forestry plants, such as flowers, shrubs, broad-leaved trees or evergreens, e.g. conifers; and on the plant propagation material, such as seeds, and the crop material of these plants. Particularly, the agriculture or horticulture crops are cereals, corn, rice, soybean and other leguminous plants, fruits and fruit trees, nuts and nut trees, citrus and citrus trees, any horticultural plants, cucurbitaceae, oleaginous plants, tobacco, coffee, tea, cacao, sugar beet, sugar cane, cotton, potato, tomato, onions, peppers, other vegetables and ornamentals. The present invention further relates to the use of the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I for treating seeds with the purpose of protecting the seeds, the germinating plants and emerged seedlings against phytopathogenic micro-organisms.
The present invention further relates to seeds which have been treated with the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula 1 for protection from phytopathogenic micro-organisms.
The present invention also relates to a method of controlling or preventing infestation of useful plants by phytopathogenic micro-organisms in agricultural crops and or horticultural crops wherein the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I, is applied to the plants, to parts thereof or the locus thereof. The effective amount of compound of Formula I ranges from 1 to 5000 gai per hectare.
Also, the present invention relates to the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I applied to a plant, plant parts or locus thereof. The present invention furthermore includes a method for treating seed, particularly seeds (dormant, primed, pregerminated or even with emerged roots and leaves) treated with the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula 1. In these methods, the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I is applied to the seeds of plants for controll ing or preventing infestation of useful plants by phytopathogenic micro-organisms in agricultural and or horticultural corps.
It is also desirable to optimize the amount of the active ingredient used so as to provide the best possible protection for the plants, the plant parts, or the seeds, the germinating plants and emerged seedl ings from attack by phytopathogenic micro-organisms, but without damaging the plants themselves by the active ingredient used. In particular, methods for the treatment of seed should also take into consideration the intrinsic phenotypes of transgenic plants in order to achieve optimum protection of the seed and the germinating plant with a minimum of crop protection compositions being employed.
One of the advantages of the present invention is that the treatment of the seeds with the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I not only protects the seed itself, but also the resulting plants after emergence, from animal pests and/or phytopathogenic harmful micro-organisms. In this way, the immediate treatment of the crop at the time of sowing or shortly thereafter protect plants as well as seed treatment in prior to sowing. It is likewise considered to be advantageous that the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula 1 can be used especially also for transgenic seed, in which case the plant which grows from this seed is capable of expressing a protein which acts against pests, herbicidal damage or abiotic stress. The treatment of such seeds with the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula 1, for example an insecticidal protein, can result in control of certain pests. Surprisingly, a further enhanced effect can be observed in this case, which additionally increases the effectiveness for protection against attack by pests, micro-organisms, weeds or abiotic stress.
The compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I is suitable for protection of seed of any plant variety which is used in agriculture, in the greenhouse, in forests or in horticulture. More particularly, the seed is that of cereals (such as wheat, barley, rye, millet and oats), oilseed rape, maize, cotton, soybeen, rice, potatoes, sunflower, beans, coffee, beet (e.g. sugar beet and fodder beet), peanut, vegetables (such as tomato, cucumber, onions and lettuce), lawns and ornamental plants. Of particular significance is the treatment of the seed of wheat, soybean, oilseed rape, maize and rice.
As also described below, the treatment of transgenic seed with the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I, is of particular significance. This refers to the seed of plants containing at least one heterologous gene which allows the expression of a polypeptide or protein, e.g. having insecticidal properties. These heterologous genes in transgenic seeds may originate, for example, from microorganisms of the species of Bacillus, Rhizobium, Pseudomonas, Serratia, Trichoderma, Clavibacter, Glomus or Gliocladium. These heterologous genes preferably originate from Bacillus sp., in which case the gene product is effective against the European corn borer and/or the Western corn rootworm. Particularly preferably, the heterologous genes originate from Bacillus thuringiensis. In the context of the present invention, the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I is applied to seeds. Particularly, the seed is treated in a state in which it is sufficiently stable for no damage to occur in the course of treatment. In general, seeds can be treated at any time between harvest and some time after sowing. It is customary to use seed which has been separated from the plant and freed from cobs, shells, stalks, coats, hairs or the flesh of the fruits. For example, it is possible to use seed which has been harvested, cleaned and dried down to a moisture content of less than 15% by weight. Alternatively, it is also possible to use seed which, after drying, for example, has been treated with water and then dried again, or seeds just after priming, or seeds stored in primed conditions or pre-germinated seeds, or seeds sown on nursery trays, tapes or paper.
When treating the seeds, it generally has to be ensured that the amount of the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I appl ied to the seed and/or the amount of further additives is selected such that the germination of the seed is not impaired, or that the resulting plant is not damaged. The compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can be applied directly, i.e. without containing any other components and without having been diluted. In general, it is preferable to apply the compositions comprising compounds of Formula I to the seed in the form of a suitable formulation. Suitable formulations and methods for seed treatment are known to those skilled in the art. The compound of Formula I can be converted to the customary formulations relevant to on-seed applications, such as solutions, emulsions, suspensions, powders, foams, slurries or combined with other coating compositions for seed, such as film forming materials, pelleting materials, fine iron or other metal powders, granules, coating material for inactivated seeds, and also ULV Formulations.
In the treatment of seeds to facilitate plantability seeds can be coated with polymer. The polymer coating is comprised of a binder, a wax and a pigment, and one or more stabilizers in an amount effective to stabilize the suspension. The binder can be a polymer selected from the group comprising of vinyl acetate-ethylene copolymer, vinyl acetate homopolymer, vinyl acetate-acrylic copolymer, vinylacryl ic, acrylic, ethylene-vinyl chloride, vinyl ether maleic anhydride, or butadiene styrene. Other simi lar polymers can be used. These formulations are prepared in a known manner, by mixing the active ingredients or active ingredient combinations with customary additives, for example customary extenders and solvents or di luents, dyes, wetting agents, dispersants, emulsifiers, antifoams, preservatives, secondary thickeners, adhesives, gibberel lins, and also water.
Useful dyes which may be present in the seed dressing Formulations usable in accordance with the invention are all dyes which are customary for such purposes. It is possible to use either pigments, which are sparingly soluble in water, or dyes, which are soluble in water. Examples include the dyes known by the names Rhodamine B, C.I. Pigment Red 1 12 and C.I. Solvent Red 1 .
Useful wetting agents which may be present in the seed dressing formulations usable in accordance with the invention are all substances which promote wetting and which are conventionally used for the formulation of active agrochemical ingredients. Usable with preference are alkylnaphthalenesulphonates, such as diisopropyl- or diisobutylnaphthalenesulphonates.
Useful dispersants and/or emulsifiers which may be present in the seed dressing formulations usable in accordance with the invention are all nonionic, anionic and cationic dispersants conventionally used for the formulation of active agrochemical ingredients. Usable with preference are nonionic or anionic dispersants or mixtures of nonionic or anionic dispersants. Useful nonionic dispersants include especially ethylene oxide/propylene oxide block polymers, alkylphenol polyglycol ethers and tristryrylphenol polyglycol ether, and the phosphated or sulphated derivatives thereof. Suitable anionic dispersants are especially lignosulphonates, polyacrylic acid salts and arylsulphonate/formaldehyde condensates.
Antifoams which may be present in the seed dressing formulations usable in accordance with the invention are all foam-inhibiting substances conventionally used for the formulation of active agrochemical ingredients. Silicone antifoams and magnesium stearate can be used with preference.
Preservatives which may be present in the seed dressing formulations usable in accordance with the invention are all substances usable for such purposes in agrochemical compositions. Examples include dichlorophene and benzyl alcohol hemi formal.
Secondary thickeners which may be present in the seed dressing formulations usable in accordance with the invention are all substances usable for such purposes in agrochemical compositions. Preferred examples include cellulose derivatives, acrylic acid derivatives, xanthan, modified clays and finely divided silica.
Adhesives which may be present in the seed dressing formulations usable in accordance with the invention are all customary binders usable in seed dressing products. Preferred examples include polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol and tylose. The formulations for on-seed applications usable in accordance with the invention can be used to treat a wide variety of different kinds of seed either directly or after prior dilution with water. For instance, the concentrates or the preparations obtainable therefrom by dilution with water can be used to dress the seed of cereals, such as wheat, barley, rye, oats, and triticaie, and also seeds of maize, soybean, rice, oilseed rape, peas, beans, cotton, sunflowers, and beets, or else a wide variety of different vegetable seeds. The formulations usable in accordance with the invention, or the dilute preparations thereof, can also be used for seeds of transgenic plants. In this case, enhanced effects may also occur in interaction with the substances formed by expression.
For treatment of seeds with the formulations usable in accordance with the invention, or the preparations prepared therefrom by adding water, all mixing units usable customarily for on-seed applications are useful. Specifically, the procedure in on-seed applications is to place the seeds into a mixer, to add the particular desired amount of the formulations, either as such or after prior dilution with water, and to mix everything until all applied formulations are distributed homogeneously on the seeds. If appropriate, this is followed by a drying operation. The application rate of the formulations usable in accordance with the invention can be varied within a relatively wide range. It is guided by the particular content of the active ingredients in the formulations and by the seeds. The application rates of each single active ingredient are generally between 0.001 and 1 5 gai per kilogram of seed, preferably between 0.01 and 5 gai per kilogram of seed.
When using the compound of Formula I as fungicides, the application rates can be varied within a relatively wide range, depending on the kind of application. The application rate of the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I, is: in the case of treatment of plant parts, for example leaves: from 0. 1 to 10000 gai/ha, preferably from 5 to 1000 gai/ha, more preferably from 5 to 100 gai/ha (in the case of application by watering or dripping, it is even possible to reduce the application rate, especial ly when inert substrates such as rockwool or perlite are used); in the case of seed treatment: from 0. 1 to 200 gai per 100 kg of seed, preferably from 1 to 150 gai per 100 kg of seed, more preferably from 2.5 to 25 gai per 100 kg of seed. in the case of soil treatment: from 0. 1 to 1 0000 gai/ha, preferably from 1 to 1 000 gai/ha. These application rates are merely by way of example and are not limiting for the purposes of the invention.
In some cases, the compound of Formula I may, at particular concentrations or appl ication rates, also be used as safeners, growth regulators or agents to improve plant properties, or as microbicides, for example as fungicides, antimycotics, bactericides, viricides (including compositions against viroids) or as compositions against phytoplasmas MLO (Mycoplasma-like organisms) and RLO (Rickettsia-like organisms).
The compound of Formula I may intervene in physiological processes of plants and can therefore also be used as plant growth regulators. Plant growth regulators may exert various effects on plants. The effect of the substances depends essentially on the time of application in relation to the developmental stage of the plant, the plant variety and also on the amounts of active ingredient applied to the plants or their environment and on the type of application. In each case, growth regulators should have a particular desired effect on the crop plants.
Growth regulating effects, comprise earlier germination, better emergence, more developed root system and/or improved root growth, increased ability of tillering, more productive tillers, earlier flowering, increased plant height and/or biomass, shorting of stems, improvements in shoot growth, number of kernels/ear, number of ears/m2, number of stolons and/or number of flowers, enhanced harvest index, bigger leaves, less dead basal leaves, improved phyllotaxy, earlier maturation/ earlier fruit finish, homogenous riping, increased duration of grain filling, better fruit finish, bigger fruit/vegetable size, sprouting resistance and reduced lodging.
Increased or improved yield is referring to total biomass per hectare, yield per hectare, kernel/fruit weight, seed size and/or hectolitre weight as well as to improved product quality, comprising: improved processabil ity relating to size distribution (kernel, fruit, etc.), homogenous riping, grain moisture, better milling, better vinification, better brewing, increased juice yield, harvestability, digestibility, sedimentation value, falling number, pod stability, storage stability, improved fiber length/strength/uniformity, increase of milk and/or meet quality of silage fed animals, adaption to cooking and frying; further comprising improved marketability relating to improved fruit/grain quality, size distribution (kernel, fruit, etc.), increased storage/shelf-life, firmness /softness, taste (aroma, texture, etc.), grade (size, shape, number of berries, etc.), number of berries/fruits per bunch, crispness, freshness, coverage with wax, frequency of physiological disorders, colour, etc.; further comprising increased desired ingredients such as e.g. protein content, fatty acids, oil content, oil quality, aminoacid composition, sugar content, acid content (pH), sugar/acid ratio (Brix), polyphenols, starch content, nutritional quality, gluten content/index, energy content, taste, etc.; and further comprising decreased undesired ingredients such as e.g. less mycotoxines, less aflatoxines, geosmin level, phenolic aromas, lacchase, polyphenol oxidases and peroxidases, nitrate content etc.
Plant growth-regulating compounds can be used, for example, to slow down the vegetative growth of the plants. Such growth depression is of economic interest, for example, in the case of grasses, since it is thus possible to reduce the frequency of grass cutting in ornamental gardens, parks and sport facilities, on roadsides, at airports or in fruit crops. Also of significance is the inhibition of the growth of herbaceous and woody plants on roadsides and in the vicinity of pipelines or overhead cables, or quite generally in areas where vigorous plant growth is unwanted.
Also important is the use of growth regulators for inhibition of the longitudinal growth of cereal. This reduces or completely eliminates the risk of lodging of the plants prior to harvest. In addition, growth regulators in the case of cereals can strengthen the culm, which also counteracts lodging. The employment of growth regulators for shortening and strengthening culms allows the deployment of higher fertilizer volumes to increase the yield, without any risk of lodging of the cereal crop.
In many crop plants, vegetative growth depression allows denser planting, and it is thus possible to achieve higher yields based on the soil surface. Another advantage of the smaller plants obtained in this way is that the crop is easier to cultivate and harvest. Reduction of the vegetative plant growth may also lead to increased or improved yields because the nutrients and assimilates are of more benefit to flower and fruit formation than to the vegetative parts of the plants.
Alternatively, growth regulators can also be used to promote vegetative growth. This is of great benefit when harvesting the, vegetative plant parts. However, promoting vegetative growth may also promote generative growth in that more assimilates are formed, resulting in more or larger fruits.
Furthermore, beneficial effects on growth or yield can be achieved through improved nutrient use efficiency, especial ly nitrogen (N)-use efficiency, phosphours (P)-use efficiency, water use efficiency, improved transpiration, respiration and/or C02 assimilation rate, better nodulation, improved Ca- metabolism etc. Likewise, growth regulators can be used to alter the composition of the plants, which in turn may result in an improvement in qual ity of the harvested products. Under the influence of growth regulators, parthenocarpic fruits may be formed. In addition, it is possible to influence the sex of the flowers. It is also possible to produce sterile pollen, which is of great importance in the breeding and production of hybrid seed.
Use of growth regulators can control the branching of the plants. On the one hand, by breaking apical dominance, it is possible to promote the development of side shoots, which may be highly desirable particularly in the cultivation of ornamental plants, also in combination with an inhibition of growth. On the other hand, however, it is also possible to inhibit the growth of the side shoots. This effect is of particular interest, for example, in the cultivation of tobacco or in the cultivation of tomatoes.
Under the influence of growth regulators, the amount of leaves on the plants can be controlled such that defoliation of the plants is achieved at a desired time. Such defoliation plays a major role in the mechanical harvesting of cotton, but is also of interest for facilitating harvesting in other crops, for example in viticulture. Defoliation of the plants can also be undertaken to lower the transpiration of the plants before they are transplanted.
Furthermore, growth regulators can modulate plant senescence, which may result in prolonged green leaf area duration, a longer grain filling phase, improved yield quality, etc.
Growth regulators can likewise be used to regulate fruit dehiscence. On the one hand, it is possible to prevent premature fruit dehiscence. On the other hand, it is also possible to promote fruit dehiscence or even flower abortion to achieve a desired mass ("thinning"). In addition, it is possible to use growth regulators at the time of harvest to reduce the forces required to detach the fruits, in order to allow mechanical harvesting or to facilitate manual harvesting.
Growth regulators can also be used to achieve faster or else delayed ripening of the harvested material before or after harvest. This is particularly advantageous as it allows optimal adjustment to the requirements of the market. Moreover, growth regulators in some cases can improve the fruit colour. In addition, growth regulators can also be used to synchronize maturation within a certain period of time. This establishes the prerequisites for complete mechanical or manual harvesting in a single operation, for example in the case of tobacco, tomatoes or coffee.
By using growth regulators, it is additionally possible to influence the resting of seed or buds of the plants, such that plants such as pineapple or ornamental plants in nurseries, for example, germinate, sprout or flower at a time when they are normally not inclined to do so. In areas where there is a risk of frost, it may be desirable to delay budding or germination of seeds with the aid of growth regulators, in order to avoid damage resulting from late frosts.
Finally, growth regulators can induce resistance of the plants to frost, drought or high salinity of the soil. This allows the cultivation of plants in regions which are normally unsuitable for this purpose. The compound of Formula I or the combination comprising the compound of Formula 1 or the composition comprising the compound of Formula I also exhibit potent strengthening effect in plants. Accordingly, they can be used for mobilizing the defences of the plant against attack by undesirable micro-organisms.
Plant-strengthening (resistance-inducing) substances in the present context are substances capable of stimulating the defence system of plants in such a way that the treated plants, when subsequently inoculated with undesirable micro-organisms, develop a high degree of resistance to these microorganisms.
Further, in context with the present invention plant physiology effects comprise the following:
Abiotic stress tolerance, comprising tolerance to high or low temperatures, drought tolerance and recovery after drought stress, water use efficiency (correlating to reduced water consumption), flood tolerance, ozone stress and UV tolerance, tolerance towards chemicals like heavy metals, salts, pesticides etc.
Biotic stress tolerance comprising increased fungal resistance and increased resistance against nematodes, viruses and bacteria. In context with the present invention, biotic stress tolerance preferably comprises increased fungal resistance and increased resistance against nematodes.
Increased plant vigor, comprising plant health / plant quality and seed vigor, reduced stand failure, improved appearance, increased recovery after periods of stress, improved pigmentation (e.g. chlorophyl l content, stay-green effects, etc.) and improved photosynthetic efficiency.
In addition, the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can reduce the mycotoxin content in the harvested material and the foods and feeds prepared therefrom. Mycotoxins include particularly, but not exclusively, the fol lowing: deoxynivalenol (DON), nivalenol, 15-Ac-DON, 3-Ac-DON, T2- and HT2- toxin, fumonisins, zearalenon, moniliformin, fusarin, diaceotoxyscirpenol (DAS), beauve icin, enniatin, fusaroproliferin, fusarenol, ochratoxins, patulin, ergot alkaloids and afiatoxins which can be produced, for example, by the following fungi : Fiisarhim spec, such as F. acuminatum, F. asiaticum, F. avenaceiim. F. crookwellen.se, F. culmorum, F. graminearum (Gibberella zeae), F. equiseti, F. fujikoroi, F. musarwn, F. oxysporum, F. proliferation, F. poae, F. pseudograminearum, F. sambacimim, F. scirpi, F. semitectum, F. solani, F. sporotrichoides, F. langsethiae, F. sub glut in an s, F. tricinctum, F. verticillioides etc., and also by Aspergillus spec, such as A. flaviis, A. parasiticus, A. nomius, A. ochraceus, A. clavatus, A. terreus, A. versicolor, Penicillium spec, such as P. verrucosum, P. viridicatum, P. citrinum, P. expansion, P. claviforme, P. roqueforti, Claviceps spec, such as C. purpurea, C. fusiformis, C. paspali, C. africana, Stachybotrys spec, and others.
The compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can also be used in the protection of materials, for protection of industrial materials against attack and destruction by phytopathogenic micro-organisms.
In addition, the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can be used as antifouling compositions, alone or in combinations with other active ingredients.
Industrial materials in the present context are understood to mean inanimate materials which have been prepared for use in industry. For example, industrial materials which are to be protected by inventive compositions from microbial alteration or destruction may be adhesives, glues, paper, wallpaper and board/cardboard, textiles, carpets, leather, wood, fibers and tissues, paints and plastic articles, cooling lubricants and other materials which can be infected with or destroyed by micro-organisms. Parts of production plants and buildings, for example cooling-water circuits, cooling and heating systems and ventilation and air- conditioning units, which may be impaired by the proliferation of micro-organisms may also be mentioned within the scope of the materials to be protected. Industrial materials within the scope of the present invention preferably include adhesives, sizes, paper and card, leather, wood, paints, cooling lubricants and heat transfer fluids, more preferably wood.
The compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I may prevent adverse effects, such as rotting, decay.; discoloration, decoloration or formation of mould.
In the case of treatment of wood the compound of Formula I or the compound of Formula I in the composition optionally comprising at least one active compatible compound may also be used against fungal diseases liable to grow on or inside timber. The term "timber" means al l types of species of wood, and all types of working of this wood intended for construction, for example solid wood, high-density wood, laminated wood, and plywood. The method for treating timber according to the invention mainly consists in contacting a composition according to the invention; this includes for example direct application, spraying, dipping, injection or any other suitable means.
In addition, the compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can be used to protect objects which come into contact with saltwater or brackish water, especially hulls, screens, nets, buildings, moorings and signalling systems, from fouling.
The compound of Formula 1 or the combination comprising the compound of Formula I or the composition comprising the compound of Formula 1 can also be employed for protecting storage goods. Storage goods are understood to mean natural substances of vegetable or animal origin or processed products thereof which are of natural origin, and for which long-term protection is desired.
Storage goods of vegetable origin, for example plants or plant parts, such as stems, leaves, tubers, seeds, fruits, grains, can be protected freshly harvested or after processing by (pre)drying, moistening, comminuting, grinding, pressing or roasting. Storage goods also include timber, both unprocessed, such as construction timber, electricity poles and barriers, or in the form of finished products, such as furniture. Storage goods of animal origin are, for example, hides, leather, furs and hairs. The compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I may prevent adverse effects, such as rotting, decay, discoloration, decoloration or formation of mould.
Micro-organisms capable of degrading or altering the industrial materials include, for example, bacteria, fungi, yeasts, algae and slime organisms. The compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I preferably act against fungi, especially moulds, wood-discoloring and wood-destroying fungi (Ascomycetes, Basidiomycetes, Deuteromycetes and Zygomycetes), and against slime organisms and algae. Examples include micro-organisms of the following genera: Altemaria, such as Alternaria tenuis; Aspergillus, such as Aspergillus niger; Chaetomium, such as Chaetomium globosum; Coniophora, such as Coniophora puetana; Lentinus, such as Lentinus tigrinus; Penicillium, such as Penicillium glaiicum; Polyporus, such as Polyporus versicolor; Aureobasidium, such as Aureobasidium pulhilans; Sclerophoma, such as Sclerophoma pityophila; Trichoderma, such as Trichoderma viride; Ophiostoma spp., Ceratocystis spp., Humicola spp., Petriella spp., Trichurus spp., Coriolus spp., Gloeophylhim spp., Pleurotus spp., Poria spp., Serpula spp. and Tyromyces spp., Cladosporium spp., Paecilomyces spp. Mucor spp., Escherichia, such as Escherichia coli; Pseudomonas, such as Pseudomonas aeruginosa; Staphylococcus, such as Staphylococcus aureus, Candida spp. and Saccharomyces spp., such as Saccharomyces cerevisae. In addition, the compound of Formula I or the combination comprising the compound of Formula 1 or the composition comprising the compound of Formula I also has very good antimycotic effects. They have a very broad antimycotic activity spectrum, especially against dermatophytes and yeasts, moulds and diphasic fungi (for example against Candida species, such as Candida albicans, Candida glabrata), and Epidermophyton floccosum, Aspergillus species, such as Aspergillus niger and Aspergillus fumigatus. Trichophyton species, such as Trichophyton mentagrophytes, Microsporon species such as Microsporon canis and audouinii. The enumeration of these fungi by no means constitutes a restriction of the mycotic spectrum covered, and is merely of illustrative character.
The compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can be used also to control important fungal pathogens in fish and Crustacea farming, e.g. saprolegnia diclina in trouts, saprolegnia parasitica in crayfish.
The compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can therefore be used both in medical and in non- medical appl ications.
The compound of Formula I or the combination comprising the compound of Formula I or the composition comprising the compound of Formula I can be used as such, in the form of their formulations or the use forms prepared therefrom, such as ready-to-use solutions, suspensions, wettable powders, pastes, soluble powders, dusts and granules. Application is accomplished in a customary manner, for example by watering, spraying, atomizing, broadcasting, dusting, foaming, spreading-on and the like. It is also possible to deploy the active ingredients by the ultra-low volume method or to inject the active ingredient preparation/the active ingredient itself into the soil. It is also possible to treat the seed of the plants.
It is possible to treat all plants and their parts in accordance with the invention, preferably with wild plant species and plant cultivars, or those obtained by.' conventional biological breeding methods, such as crossing or protoplast fusion, and also parts thereof. In a further preferred embodiment, transgenic plants and plant cultivars obtained by genetic engineering methods, if appropriate in combination with conventional methods (Genetically Modified Organisms), and parts thereof are treated. The terms "parts" or "parts of plants" or "plant parts" have been explained above. More preferably, plants of the plant cultivars which are commercially available or are in use are treated in accordance with the invention. Plant cultivars are understood to mean plants which have new properties ("traits") and have been obtained by conventional breeding, by mutagenesis or by recombinant DNA techniques. They can be cultivars, varieties, bio- or genotypes. The method of treatment according to the invention can be used in the treatment of genetically modified organisms (GMOs), e.g. plants or seeds. Genetically modified plants (or transgenic plants) are plants of which a heterologous gene has been stably integrated into genome. The expression "heterologous gene" essentially means a gene which is provided or assembled outside the plant and when introduced in the nuclear, chloroplastic or mitochondrial genome gives the transformed plant new or improved agronomic or other properties by expressing a protein or polypeptide of interest or by downregulating or silencing other gene(s) which are present in the plant (using for example, antisense technology, cosuppression technology, RNA interference - RNAi - technology or microRNA - miRNA - technology). A heterologous gene that is located in the genome is also called a transgene. A transgene that is defined by its particular location in the plant genome is called a transformation or transgenic event.
Plants and plant cultivars which are preferably to be treated according to the invention include all plants which have genetic material which impart particularly advantageous, useful traits to these plants (whether obtained by breeding and/or biotechnological means).
Plants and plant cultivars which are also preferably to be treated according to the invention are resistant against one or more biotic stresses, i.e. said plants show a better defense against animal and microbial pests, such as against nematodes, insects, mites, phytopathogenic fungi, bacteria, viruses and/or viroids.
Plants and plant cultivars which may also be treated according to the invention are those plants which are resistant to one or more abiotic stresses. Abiotic stress conditions may include, for example, drought, cold temperature exposure, heat exposure, osmotic stress, flooding, increased soil salinity, increased mineral exposure, ozone exposure, high light exposure, limited availability of nitrogen nutrients, limited availability of phosphorus nutrients, shade avoidance.
Plants and plant cultivars which may also be treated according to the invention, are those plants characterized by enhanced yield characteristics. Increased yield in said plants can be the result of, for example, improved plant physiology, growth and development, such as water use efficiency, water retention efficiency, improved nitrogen use, enhanced carbon assimilation, improved photosynthesis, increased germination efficiency and accelerated maturation. Yield can furthermore be affected by improved plant architecture (under stress and non-stress conditions), including but not limited to, early flowering, flowering control for hybrid seed production, seedling vigor, plant size, internode number and distance, root growth, seed size, fruit size, pod size, pod or ear number, seed number per pod or ear, seed mass, enhanced seed filling, reduced seed dispersal, reduced pod dehiscence and lodging resistance. Further yield traits include seed composition, such as carbohydrate content and composition for example cotton or starch, protein content, oil content and composition, nutritional value, reduction in anti-nutritional compounds, improved processability and better storage stability.
Plants that may be treated according to the invention are hybrid plants that already express the characteristic of heterosis or hybrid vigor which results in generally higher yield, vigor, health and resistance towards biotic and abiotic stresses).
Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated according to the invention are herbicide-tolerant plants, i.e. plants made tolerant to one or more given herbicides. Such plants can be obtained either by genetic transformation, or by selection of plants containing a mutation imparting such herbicide tolerance. Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are insect-resistant transgenic plants, i.e. plants made resistant to attack by certain target insects. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such insect resistance.
Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are tolerant to abiotic stresses. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such stress resistance.
Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention show altered quantity, quality and/or storage-stability of the harvested product and/or altered properties of specific ingredients of the harvested product. Plants or plant cultivars (that can be obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants, such as cotton plants, with altered fiber characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered fiber characteristics.
Plants or plant cultivars (that can be obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants, such as oilseed rape or related Brassica plants, with altered oil profile characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered oil profile characteristics. Plants or plant cultivars (that can be obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants, such as oilseed rape or related Brassica plants, with altered seed shattering characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered seed shattering characteristics and include plants such as oilseed rape plants with delayed or reduced seed shattering.
Plants or plant cultivars (that can be obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants, such as tobacco plants, with altered post-translational protein modification patterns.
CHEMISTRY EXAMPLES: The compounds of Formula 3 and 3A can be prepared by one or more of the following methods and variations as described in Schemes 1 - 13. The definitions of J, G, Z, Q and n in the compounds of Formula 1 -24 below are as defined above in the detailed description unless otherwise noted.
Scheme 1
R
Figure imgf000051_0001
1 W=0 2 3 W=0
1a W=S 3a W=S
As shown in Scheme 1 , the preparation of a compound of Formula 3 or 3a involves coupling of an acid of Formula 1 or la respectively with an amine of Formula 2 (or its acid salt) in the presence of a dehydrative coupling reagent such as dicyclohexylcarbodiimide (DCC) or l -(3-dimethylaminopropyl)-3- ethyicarbodiimide hydrochloride (EDC) O-benzotriazol-l-yl-tetramethy!uronium hexafluoro-phosphate (HBTU) or l -[bis(dimethylamino)methylene]- l H- l ,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU). Polymer-supported reagents such as polymer-bound cyclohexylcarbodi imide can also be used as coupling agent. The reaction is typically carried out at 0 to 40 °C in a solvent such as dichloromethane or acetonitrile or N, N-dimethylformamide in the presence of a base such as triethylamine or diisopropylethylamine. Alternatively, the compound of formula 3a can be obtained from the compound of Formula 3 by thiating the compound of Formula 3 using a thiating reagent such as phosphorus pentasulfide or 2, 4-bis (4- mefhoxyphenyl)-l, 3-dithia-2, 4-diphosphetane-2, 4-disulfide (Lawesson's reagent).
The acids of Formula 1 and la are known or can be prepared by methods known to one skilled in the art. For example, R4CH2COOH wherein R4 is a heterocycl ic ring linked through nitrogen can be prepared by reacting the corresponding R4H compound with a halo acetic acid or ester in the presence of a base; followed by hydrolysis.
Scheme 2
Figure imgf000052_0001
4 2 The amine compound of Formula 2 can be prepared from the protected amine compound of Formula 4 wherein Y i is an amine-protecting group.
The compound of Formula 4 is converted into the compound of Formula 2 by a suitable method for removing protecting groups described in the literature (Protective Groups in Organic Synthesis"; Theodora W. Greene, Peter G. M. Wuts; Wiley-Interscience; Third Edition; 1999; 494-653). For example, tert-Butoxycarbonyl and benzyloxycarbonyl protecting groups can be removed in an acidic medium for example by using hydrochloric acid or trifluoroacetic acid. Acetyl protecting groups can be removed under basic conditions for example by using potassium carbonate or cesium carbonate. Benzylic protecting groups can be removed hydrogenolytically by using hydrogen in the presence of a catalyst for example palladium on activated carbon. After the reaction is completed, the compound of Formula 2 is separated from the reaction mixture by one of the customary separation techniques. If necessary, the compounds are purified by recrystallization or chromatography, or can, if desired, also be used in the next step without prior purification. It is also possible to isolate the compound of Formula 2 as a salt, for example as a salt of hydrochloric acid or of trifluoroacetic acid.
Scheme 3
Figure imgf000053_0001
As shown in Scheme 3, a compound of Formula 4 wherein J-Q contains amine as one of the substituent involves coupling of an acid of Formula 5 with an amine of J-Q (or its acid salt) in the presence of a dehydrative coupling reagent such as dicyclohexylcarbodiimide (DCC) or 1 -(3-dimefhylaminopropyl)-3- etbylcarbodiimide hydrochloride (EDC) O-benzotriazol-l-yl-tetramethyluronium hexafluoro-phosphate (HBTU) or l -[Bis(dimethylamino)methylene]- l H- l ,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU). Polymer-supported reagents such as polymer-bound cyclohexylcarbodiimide can also be used as coupling agent. The reaction is typically carried out at 0 to 40 oC in a solvent such as dichloromethane or acetonitrile or N, N-dimethylformamide in the presence of a base such as triethylamine or diisopropylethylamine.
Scheme 4
Figure imgf000053_0002
The compound of Formula 5 can be prepared by hydrolyzing a compound of Formula 6 using a base or an acid. Preferred bases for the conversion of the compound of Formula 6 into the compound of Formula 5 are sodium hydroxide, lithium hydroxide, potassium hydroxide and the like. Preferred acids for the conversion of the compound of Formula 6 into the compound of Formula 5 are hydrochloride acid, sulfuric acid, acetic acid, trifluroroacetic acid and the like. Preferred solvents for the hydrolysis reactions are water or ethanol or tetrahydrofuran.
Scheme 5
f
Figure imgf000053_0003
8 9 6
X=l or Br or CI
Synthesis of the compound of Formula 6 is carried out by Suzuki reaction involving Pd-catalyzed cross- coupling the compound of Formula 8 with a boronic acid or ester of Formula 9, as shown in Scheme 5. Several catalysts are reported for this type of transformation, a typical catalyst being tetrakis (triphenylphosphine) palladium or bis (triphenylphosphine) palladium chloride. Solvents such as tetrahydrofuran, acetonitrile, diethyl ether, dioxane and dioxanerwater mixture are suitable for Suzuki reaction. The Suzuki reaction and related coupling procedures offer many alternatives for creation of the C-G bond. For references see C. A. Zificsak and D. J. Hlasta, Tetrahedron 2004, 60, 8991 -9016. For a thorough review of palladium chemistry applicable to the synthesis of C-G bonds see J. J. Li and G. W. Gribble, editors, Palladium in Heterocyclic Chemistry: A Guide for the Synthetic Chemist, Elsevier: Oxford, UK, 2000. Many variations of catalyst type, base and reaction conditions are known in the literature for Suzuki reaction.
Scheme 6
Figure imgf000054_0001
6 6a
Reduction of the endocyclic double bond is carried out using catalytic hydrogenation to give a compound of Formula 6a. Pd/C is the preferred catalysts. For references of such hydrogenation reactions see Sarah Sulzer-Mosse et al Bioorganic & Medicinal Chemistry 2015 23 2129-2138.
Scheme 7
Y,
Figure imgf000054_0002
7 8 6b
Z= N
A compound of Formula 6b can be prepared by a compound of Formula 7 with a compound of Formula 8 in the presence of a base. Suitable bases for such reaction include sodium hydride or potassium carbonate and the reaction is carried out in a solvent such as N, N-dimethylformamide or acetonitrile at 0 to 80 °C. Suitable leaving group Y2 in the compound of Formula 8 include bromide, iodide, mesylate, triflate and the like, and the compound of Formula 8 can be prepared from the corresponding compounds wherein Y2 is hydroxy, using general methods known in the art.
Scheme 8
Figure imgf000055_0001
10 J-Q
The compound of Formula J-Q can be prepared by reacting a compound of Formula 9 with ammonium carbamate in the presence of PhI(OAc)2 in methanol. Different solvents such as acetonitrile, toluene, tetrahydrofuran can also be used for the preparation of the compound of Formula J-Q conversion. Ammonium acetate and ammonia in methanol solution is also suitable as a nitrogen-source for this kind of conversion.
Scheme 9
Figure imgf000055_0002
Outline for the preparation of a compound of Formula la is described in Scheme 9. A suitably substituted compound of Formula 11 was purchased commercially or can be prepared from the corresponding chloro derivatives using known methods in the literature. Suitable reagents for this conversion can be sulfuric acid or hydrochloric acid or sodium hydroxide. Please refer PCT Patent Application Publication WO2007/39563 WO2014/71044 Lavecchia; Berteina-Raboin; Guillaumet, and Tetrahedron Letters, 2004, 45, 35, 6633-6636. The compound of Formula 11 can be further functionalized using known methods in the literature like chlorination, bromination, trifluromethylation to obtain appropriately substituted heterocyclic ring like pyridone (refer Formula 12). References for the said transformations are Zhang, Pei-Zhi et al Tetrahedron, 2016 72(23), 3250-3255; Canibano; Rodriguez; Santos; Sanz-Tejedor; Carreno; Gonzalez; Garcia-Ruano Synthesis, 2001, 14, 2175-2179, and WO2004/50637. A substituted heterocyclic ring containing a pyridone-l ike moiety can be acylated by reacting with an alkyl ester containing a suitable leaving group such as halogen or mesylate or tosylate in the presence of a base such as potassium carbonate or cesium carbonate in a polar solvent such as N, N-dimethylformamide or NMP with or without heating to obtain the compound of Formula 13. Typically mixtures of O- and N- alkylated products are obtained and the two regio-isomeric products can be separated by means of silica gel or reverse phase chromatography. The addition of l ithium salts, for example lithium chloride to the reaction mixture can be employed to favor N-alkylation over O-alkylation. The obtained aikyl ester can be further hydrolyzed to the corresponding acids by heating or stirring at room temperature in the presence of lithium hydroxide or sodi um hydroxide in solvents like ethanol or water to obtain the novel compound with Formula l a.
Scheme 10
Figure imgf000056_0001
The preparation of a compound of Formula 15 can be achieved by reacting substituted acetoacetic ester with alkyl hydrazine of Formula 14 with excellent regioselectivity. The compound of Formula 15 can then be selectively alkylated using alkyl halides with or without base to obtain a compound of Formula 16.
The compound of Formula 16 can be further functionalized using known methods in the literature like chlorination or bromination or trifluromethylation to obtain appropriately substituted compound of Formula 17.
The comound of Formula 17 can be further hydrolyzed by heating or stirring at room temperature in the presence of lithium hydroxide or sodium hydroxide or potassium hydroxide in solvents like ethanol or water to obtain the novel compound of Formula lb. The compound of Formula lb can be used with or without converting it into corresponding acyl chloride.
Scheme 11
Figure imgf000056_0002
A compound of Formula 18 and hydrazines are commercially available or can be prepared by methods known in the literature. The comound of Formula 18 is reacted with hydrazines to form intermediate of Formula 19. For relevant references see Katrizky et al., ./. Chem. Soc. Perkin Trans. II, 1987, 969-975; Muller et al ., Monatshefte fuer Chemie 1958, 89, 23-35 ; WO2006/1 16713 and US2007/0049574. A compound of Formula 19a wherein R1 is halogen can be prepared from the compound of Formula 19 (R1 is H) by halogenating it with a halogenating reagent as shown in Scheme 1 1. A variety of halogenating reagents known in the literature are suitable for this method including, for example, N- halosuccinimides (e.g., NBS, NCS, NIS), elemental halogen (e.g., Cl2, Br2, I2), phosphorus oxyhalides, phosphorus trihalides, phosphorus pentahalides, thionyl chloride, sulfuryl chloride, bis(pyridine)iodonium(]) tetrafJuoroborate, tetramethylammonium iodide chloride, tetrafluoroborate and sulfur tetrafluoride. N-halosuccinimides are particularly more suitable for such halogenation reactions. Typically, the reaction is carried out in a suitable solvent such as N, N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane, acetic acid, chloroform, benzene, xylenes, chlorobenzene, tetrahydrofuran, 1 , 4 dioxane or the like. Optionally, an organic base such as triethylamine, pyridine, N, N-dimethylaniline or the like can be added. Catalyst such as N, N-dimethylforrnamide or 2, 2'-azobis (2- methylpropionitrile) (AIBN) can also be used to catalyze such reaction. Typically, reaction temperatures range from about room temperature (e.g., 25 °C) to 1 50 °C. For representative procedures see US2007/0049574; WO2006/071730; Campos et al., Tetrahedron Letters 1997 and Gibert et al., Pharmaceutical Chemistry Journal, 2007, 41 (3), 154-156. Compounds of Formula 20 and 20a, respectively can be prepared by treating the compounds of Formula 19 and 19a with ethyl bromo acetate preferably with bases as shown in the Scheme 1 1 . Typical ly, the reaction is carried out in a suitable solvent such as N, N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane, tetrahydrofuran, acetone, 1 , 4 dioxane or the like. Optionally, an organic base such as triethylamine, pyridine, or inorganic bases such as potassium carbonate, cesium carbonate, sodum carbonate or the like can be used.
The compounds of Formula 20 and 20a can be hydrolyzed by treating it with sodium hydroxide or lithium hydroxide or potassium hydroxide to obtain a compound of Formula lc as shown in the Scheme 1 1 . Preferred solvents for the hydrolysis are water or ethanol or tetrahydrofuran.
Scheme 12
Figure imgf000058_0001
A compound of Formula 12 and hydrazines (R2NHNH2) are commercially available or can be prepared by methods known in the literature. The preparation of a compound Formula 21 can be carried out using dimethyl sulphate in the presence of bases like potassium carbonate, cesium carbonate, sodium carbonate or the like as explained in Journal of Heterocyclic Chemistry, 1993, 30, 1 , 49-54.
The compound of Formula 21 can be reacted with hydrazine (R2NHNH2) in protic solvents like ethanol or methanol to obtain a compound of Formula 22a.
A compound of Formula 22b wherein R1 is halogen can be prepared from the compound of Formula 22a (R1 is H) by halogenating it with a halogenating reagent as shown in Scheme 1 1. A variety of halogenating reagents known in the literature are suitable for this method including, for example, N- halosuccinimides (e.g., NBS, NCS, NIS), elemental halogen (e.g., Cl2, Br2, 12), phosphorus oxyhalides, phosphorus trihalides, phosphorus pentahalides, thionyl chloride, sulfuryl chloride, bis(pyridine)iodonium(I) tetrafluoroborate, tetramethylammonium iodide chloride, tetrafluoroborate and sulfur tetrafluoride. N-halosuccinimides are particularly more suitable for such halogenation reactions. Typically, the reaction is carried out in a suitable solvent such as N, N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane, acetic acid, chloroform, benzene, xylenes, chlorobenzene, tetrahydrofuran, 1 , 4 dioxane or the like. Optionally, an organic base such as triethylamine, pyridine, N, N-dimethylaniline or the like can be added. Catalyst such as N, N-dimethylforrnamide or 2, 2'-azobis (2- methylpropionitrile) (AIBN) can also be used to catalyze such reaction. Typically, reaction temperatures range from about room temperature (e.g., 25 °C) to 1 50 °C. For representative procedures see US2007/0049574; WO2006/071730; Campos et al., Tetrahedron Letters 1997 and Gibert et al., Pharmaceutical Chemistry Journal, 2007, 41 (3), 1 54- 1 56.
Compounds of Formula 23a and 23b, respectively can be prepared by treating the compounds of Formula 22a and 22b, with ethyl bromo acetate preferably with bases as shown in the Scheme 12. Typically, the reaction is carried out in a suitable solvent such as N, N-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane, tetrahydrofuran, acetone, 1 , 4 dioxane or the like. Optionally, an organic base such as triethylamine, pyridine, or inorganic bases such as potassium carbonate, cesium carbonate, sodum carbonate or the l ike can be used.
Compounds of Formula 23a and 23b can be hydrolyzed by treating it with sodium hydroxide or lithium hydroxide or potassium hydroxide to obtain a compound of Formula la as shown in the scheme 12. Preferred solvents for the hydrolysis are water or ethanol or tetrahydrofuran.
Scheme 13
Figure imgf000059_0001
Outline for preparation of the comopund of Formula lc is described in Scheme 13. Suitably substituted compound of Formula 11 can purchased commercially or can be prepared from the corresponding chloro derivatives using known methods in the literature. Suitable reagents for these conversions will be Sulfuric acid, Hydrochloric acid, sodium hydroxide. Please refer WO2007/39563 WO2014/71044 Lavecchia; Berteina-Raboin; Guillaumet, Tetrahedron Letters, 2004, 45, 35 6633-6636.
Substituted compounds of Formula 1 1 can be further functionalized using known methods in the literature like chlorination, Bromination, Trifluromethylation to get appropriately substituted heterocyclic ring like Pyridone (Formula 1 2) References for the said transformations are Zhang, Pei-Zhi et al Tetrahedron, 2016,72(23), 3250-3255; Canibano; Rodriguez; Santos; Sanz-Tejedor; Carreno; Gonzalez; Garcia-Ruano Synthesis, 2001, 14,21 75 - 21 79, PCT Patent Application Publication WO2004/50637.
A substituted functional ized heterocyclic ring containing a pyridone-like moiety can be alkylated by reaction with an alkyl ester containing a suitable leaving group such as halogen, mesylate or tosylate, in the presence of a base such as Ag2C03 or Cs2C03, in a polar sol!vent such as N, N-dimethylformamide or NMP, or non-polar solvent such as toluene, xylene with or without heating.to get the compound of Formula 24. Typically mixtures of O- and N-alkylated products are obtained, and the two regio-isomeric products can be separated by means of Si02 gel or reverse phase chromatography. The addition of lithium salts, for example LiCl, to the reaction mixture can be employed to favor N- vs. O- alkylation. The obtained alkyl ester can be further hydrolyzed to the corresponding acids by heating or stirring at room temperature in the presence of Lithium hydroxide or sodium hydroxide in solvents l ike ethanol, water to get the novel compounds with formula 1 . Scheme 14
Figure imgf000060_0001
6a 25
As shown in Scheme 14, synthesis of a compound of Formula 25 involves simple one-pot aromatic ethyl ester reduction into the corresponding alcohol using NaBH4-MeOH system. The aromatic alcohols were obtained by the method explained in the ARKIVOC, 2006, 128- 133, involving the reduction of aromatic ethyl esters in 1 5-60 minutes after refluxing in THF. The respective alcohol products were isolated after aqueous workup in good yield.
Scheme 15
Figure imgf000060_0002
A compound of Formula 26 can be prepared by bromination of the compound of Formula 25 using CBr /PPh . PBr3 can also be used as brominating agent.
Scheme 16
Figure imgf000060_0003
27
A compound of Formula 27 can be synthesised by treating the compound of Formula 26, with sulfoximine (J-Q) in the presence of a base like K'Obu, NaH, and K2C03 in solvents like DMF and DMSO.
Scheme 17
Figure imgf000061_0001
Synthesis of a compound of Formula 28 can be achieved by treating the compound of Formula 5 and suitable J-Q in presence of triethylamine and diphenylphosphoryl azide (DPPA) as a source of azide in solvents like toluene. EXAMPLE 1
Preparation of N-((2,6-difluorophenyl)(methyl)(oxo)- 6-sulfanylidene)-2-(l-(2-(5-methyl-3- (trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide (Compound 15)
Step A: Preparation of ethyl 2-bromo-l,3-thiazole-4-carboxylate
To a solution of ethyl 2-aminothiazole-4-carboxylate ( 100 g, 581 mmol) and copper (II) bromide (195 g, 871 mmol) in acetonitrile ( 1000 mL), tert-butylnitrite ( 100 mL, 871 mmol) was added dropwise at 0 °C. The reaction mixture was warmed to 25 °C and stirred for 12 h. The reaction mixture was diluted with ethyl acetate ( 1000 mL) and water (3000 mL) and acidified to pH 2 using IN hydrochloric acid. The aqueous layer was separated and extracted thrice with ethyl acetate (500 mL). The combined organic layer was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to obtain crude ethyl 2-bromo-l , 3-thiazole-4-carboxylate which was purified by recrystalhzation using hexane as a solvent to obtain pure ethyl 2-bromo- l , 3-thiazole-4-carboxylate ( 1 1 5 g, 84% yield).
Ή-NMR (400 MHz, DMSO-rf6) δ 8.52 (s, 1 H), 4.29 (q, J = 7.1 Hz, 2H), 1 .29 (t, J = 7.1 Hz, 3H) MS: m/z = 235.90. [M+l ]
Step B: Preparation of ethyl 2-(l-(tert-butoxycarbonyl)-l,2,3,6-tetrahydropyridin-4-yl)thiazole-4- carboxylate
Bis(triphenylphosphine)palladium(II)chloride (9.5 g, 13.5 mmol), tert-butyl 4-(4,4,5,5-tetramethyl- l ,3,2- dioxaborolan-2-yl)-3,6-dihydropyridine- l (2/J)-carboxylate ( 100 g, 323 mmol) and a solution of sodium carbonate (86 g, 809 mmol) in water ( 1 00 mL) were consecutively added to a solution of ethyl 2- bromothiazole-4-carboxylate (63.6 g, 270 mmol) in dioxane (200 mL). The reaction mixture was heated to 85 °C for 12 h. The reaction mixture was cooled to 25 °C, filtered through celite bed and washed with methanol. The filtrate was concentrated under reduced pressure and the residue obtained after concentration was purified by column chromatography using 45% ethyl acetate in hexane as an eluent to obtain ethyl 2-( 1 -(tert-butoxycarbonyl)- l ,2,3,6-tetrahydropyridin-4-yl)thiazole-4-carboxylate (50 g, 55% yield).
Ή-NMR (400 MHz, DMSO-c/6) δ 8.40 (s, 1 H), 6.63 (s, 1 H), 4.26 (q, J = 7.0 Hz, 2H), 4.01 (s, 2H), 3.49 (t, ./ = 5.7 Hz, 2H), 2.54 (d, J = 1 .7 Hz, 2H), 1.39 (d, J = 6.4 Hz, 9H), 1 .24-1.28 (m, 3H). MS: m/z = 339 [M+l ].
Step C: Preparation of ethyl 2-(l-(tert-butoxycarbonyl)piperidin-4-yl)thiazole-4-carboxylate
To a solution of ethyl 2-( l -(tert-butoxycarbonyl)- l ,2,3,6-tetrahydropyridin-4-yl)thiazole-4-carboxylate ( 12.8 g, 37.8 mmol) in ethanol (200 mL), was added a suspension of 10%> palladium on charcoal ( 16.1 g, 1 5.1 mmol) in ethanol ( 100 mL). The reaction mixture was maintained under hydrogen pressure of 70 bar at 65 °C for 12 h. The reaction mixture was cooled to 25 °C and filtered. The filtrate was concentrated to obtain ethyl 2-( l -(tert-butoxycarbonyl) piperidin-4-yl)thiazole-4-carboxylate (9.0 g, 72% yield).
'H-NMR (400 MHz, DMSO-i/6) δ 8.41 (s, 1 H), 4.28 (q, J = 7.1 Hz, 2H), 4.00 (d, J = 12.5 Hz, 2H), 3.20- 3.27 (m, 1 H), 2.87 (s, 2H), 2.00-2.03 (m, 2H), 1.53 (ddd, J = 24.7, 12.2, 4.1 Hz, 2H), 1 .37- 1.43 (m, 9H), 1 .28 (t, J= 7.1 Hz, 3H). MS: m/z = 341 .10 [M+l ].
Step D: Preparation of 2-(l-(tert-butoxycarbonyl)piperidin-4-yl)thiazole-4-carboxylic acid
To a stirred solution of ethyl 2-( l -(tert-butoxycarbonyl)piperidin-4-yl)thiazole-4-carboxylate ( 1 g, 3.2 mmol) in methanol-water mixture (40 mL), lithium hydroxide (0.3 g, 12.9 mmol) was added. The reaction mixture was stirred at 25 °C for 2 h. The reaction mixture was concentrated by evaporating methanol, diluted with water and acidified with IN hydrochloric acid. The precipitate was filtered and dried to obtain 2-( l -(tert-butoxycarbonyl)piperidin-4-yl)thiazole-4-carboxylic acid ( 1.0 g, 89%> yield).
Step E: Preparation of tert-butyl 4-(4-(((2,6-difluorophenyl)(methyl)(oxo)-λ6- sulfanylidene)carbamoyI)thiazol-2-yl)piperidine-l-carboxylate
To a solution of 2-( l -(tert-butoxycarbonyl)piperidin-4-yl)thiazole-4-carboxylic acid ( 1 g, 3.2 mmol) in N, N-dimethylformamide (8 mL), l -[bis(dimethylamino)methylene]- l H- l ,2,3-triazolo[4,5-b]pyridinium 3- oxid hexafluorophosphate (HATU) ( 1 .8 g, 4.8 mmol) and N, N-diisopropylethylamine (2.2 mL, 12.8 mmol) were added under inert atmosphere. The resulting reaction mixture was stirred for 10 min. (2,6- difluorophenyl)(imino)(methyl)- 6-sulfanone (0.6 g, 3.2 mmol) was added and stirred for 16 h. After completion of the reaction, the reaction mixture was diluted with water ( 10 mL) and extracted twice with ethyl acetate ( 1 5 mL). The combined ethyl acetate layer was washed with brine, dried over anhydrous sodium sulphate, concentrated under reduced pressure and purified by column chromatography using 80% ethyl acetate in hexane as eluent to obtain tert-butyl 4-(4-(((2,6-difluoiOphenyl)(methyl)(oxo)- 6- sulfanyl idene)carbamoyl)thiazol-2-yl)piperidine- l -carboxylate (0.5 g, 1 .0 mmol, 32% yield).
Step F: Preparation of N-((2,6-difluorophenyI)(methyl)(oxo)^6-sulfanylidene)-2-(piperidin-4-yI) thiazole-4-carboxamide
To a solution of tert-butyl 4-(4-(((2,6-difluorophenyl)(methyl)(oxo)- 6-sulfanylidene)carbamoyl)thiazol- 2-yl)piperidine- l -carboxylate (550 mg, 1.1 mmol) in dichloromethane (10 mL), trifluoroacetic acid (3.5 inL, 45.3 mmol) was added within 1 5 minutes. The resulting reaction mixture was stirred at 25 °C for 1 h to obtain a clear solution. The reaction mixture was concentrated under reduced pressure and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The ethyl acetate layer was dried over anydrous sodium sulphate and concentrated to obtain N-((2,6-difluorophenyl)(methyl)(oxo)-X6- sulfanylidene)-2-(piperidin-4-yl) thiazole-4-carboxamide (400 mg, 80% yield).
Step G: Preparation of N-((2,6-difluorophenyl)(methyI)(o o)-λ6-sulfanylidene)-2-(l-(2-(5-methyl-3- (trifluoromethyl)-lH-pyrazol-l-yI)acetyl)piperidin-4-y])thiazole-4-carboxamide (Compound 15) To a solution of 2-(5-methyl-3-(trifluoromethyl)-l H-pyrazol- l -yl)acetic acid ( 129 mg, 0.6 mmol) in N, N-dimethy!formamide ( 5 mL), l -[bis(dimethylamino)methylene]- l H-l ,2,3-triazolo[4,5-b]pyridinium 3- oxid hexafluorophosphate (HATU) (258 mg, 0.7 mmol) and N, N-diisopropylethylamine (0.6 mL, 3.4 mmol) was added. The resulting clear solution was stirred for 10 min at 25 °C. N-((2,6- difluorophenyl)(methyl)(o o)-λ6-sulfanylidene)-2-(piperidin-4-yl)thiazole-4-cai·boxamide (21 8 mg, 0.6 mmol) was added and the resulting yellow solution was stirred for 16 h at 25 °C. After completion of the reaction, the reaction mixture was quenched with a brine solution ( 1 50 mL). The reaction mixture was extracted twice with ethyl acetate (50 mL). The ethyl acetate layer was concentrated and the residue was purified using column chromatography using 80% ethyl acetate in hexane as an eluent to obtain N-((2,6- difluorophenyl)(methyl)(oxo)- 6-sulfanylidene)-2-( l -(2-(5-methyl-3-(trifluoromethyl)- l H^
yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide (26 mg, 0.05 mmol, 8% yield).
Ή-NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1 H), 7.80-7.87 (m, 1 H), 7.38 (t, J = 9.0 Hz, 2H), 7.1 8 (t, J = 53.3 Hz, 1 H), 7.04 (t, J = 54.2 Hz, 1 H), 6.92-7.22 (m, 1 H), 5.40 (dd, J = 33.2, 16.6 Hz, 2H), 4.35 (d, J = 13.0 Hz, 1 H), 3.97 (d, J = 13.0 Hz, 1 H), 3.72 (s, 3H), 3.25 (t, J = 1 1 .9 Hz, 1 H), 2.79-2.85 (m, 1 H), 2.08 (s,3H), 1 .78 (dd, J = 28.0, 1 5.0 Hz, 1 H), 1 .50- 1 .59 (m, 1 H) EXAMPLE 2 Preparation of 2-(l-(2-(3,5-bis(dilluoroniethyl)-lH-pyrazol-l-yl)acetyI)piperidin-4-yl)-N-((3- bromophenyl)(methyl)(oxo)^6-sulfanylidene)thiazole-4-carboxamide (Compound 2)
To a solution of N-((3-bromophenyl)(methyl)(oxo)^6-sulfanylidene)-2-(pipendin-4-yl)thiazole-4- carboxamide (0.3 g, 0.6 mmol) in N, N-dimethylformamide (8 mL), N, N-di isopropylethylamine (0.5 mL, 3.0 mmol) was added and stirred for 5 min. To the resulting reaction mixture, 1 - [bis(dimethylamino)methylene]- l H- l ,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) (0.3 g, 0.9 mmol) and 2-(3,5-bis(difluoromethyl)- l H-pyrazol- l -yl)acetic acid (0.2 g, 0.6 mmol) was added and the reaction mixture was allowed to stir at 25 °C for 12 h under inert atmosphere. The reaction mixture was diluted with water and extracted twice with ethyl acetate (30 mL). The combined ethyl acetate layer was washed with brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude product was purified using column chromatography 80% ethyl acetate in hexane as an eluent to obtain 2-(l -(2-(3,5-bis(difluoromethyl)- l H-pyrazol- l -yl)acetyl)piperidin-4-yl)-N- ((3 bromophenyl)(methyl)(oxo)- 6-sulfanylidene)thiazole-4-carboxamide (0.1 g, 0.2 mmol, 34% yield).
Ή-NMR (400 MHz, DMSO-i 6) δ 8.29 (s, 1 H), 8.17 (s, 1 H), 8.00 (ddd, ./ = 18.7, 7.9, 0.8 Hz, 2H), 7.64 (t, 7 = 7.9 Hz, 1 H), 7.02-7.30 (m, 2H), 6.89 (d, .7 = 4.0 Hz, 1 H), 5.38 (dd, J = 33.2, 17.0 Hz, 2H), 4.34 (d, J = 13.1 Hz, 1 H), 3.95 (d, J = 13.4 Hz, 1 H), 3.64 (s, 3H), 3.33-3.37 (m, 1 H), 3.21 -3.27 (m, 1 H), 2.81 (t, J = 1 1 .9 Hz, 1 H), 2.07 (t, J = 13.5 Hz, 2H), 1 .77 (q, J = 1 1 .7 Hz, 1 H), 1 .50- 1 .59 (m, 1 H)
EXAMPLE 3
Preparation of N-((2,6-dimethylphenyl)(ethyl)(oxo)-X6-sulfanylidene)-2-(l-(2-(5-methyl-3- (trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide (Compound 9)
To a solution of N-((2,6-dimethylphenyl)(ethyl)(oxo)^6-sulfanylidene)-2-(piperidin-4-yl)thiazole-4- carboxamide (0.3 g, 0.6 mmol) in N, N-dimethylformamide (4 mL), N, N-diisopropylethylamine (0.6 mL, 3.2 mmol) was added and stirred for 5 min. To the resulting reaction mixture, 1 - [bis(dimethylamino)methylene]-l H-l ,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) (0.4 g, 1 .0 mmol) and 2-(5-methyl-3-(trifluoromethyl)- l H-pyrazol- l -yl)acetic acid (0.1 g,' 0.6 mmol) were added and the reaction mixture was allowed to stirr at 25 "C for 1 2 h under inert atmosphere. The reaction mixture was diluted with water and extracted twice with ethyl acetate (30 mL).The combined ethyl acetate layer was washed with brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude product was purified by column chromatography 80% ethyl acetate in hexane as an eluent to obtain N-((2,6-dimethylphenyl)(ethyl)(oxo)- 6-sulfanyl idene)-2-( l -(2-(5-methyl-3- (trifluoromethyl)- l H-pyrazol- l -yl)acetyl)piperidin-4-yl)thiazo]e-4-carboxamid (100 mg, 0.2 mmol, 27% yield).
Ή-NMR (400 MHz, DMSO-c/6) δ 8.25 (s, 1 H), 7.44 (t, J = 7.6 Hz, 1 H), 7.27 (d, J = 7.6 Hz, 2H), 6.49 (s, 1 H), 5.27 (dd, ./ = 38.1 , 1 7.0 Hz, 2H), 4.35 (d, ./ = 13.1 Hz, 1 H), 3.95 (d, J = 13.1 Hz, 1 H), 3.62 (dq, J = 30.0, 7.3 Hz, 2H), 3.34-3.36 (m, 1 H),3.21 -3.27 (m, 1 H), 2.78-2.84 (m, 1 H), 2.62 (s, 6H), 2.19 (d, J = 3.1 Hz, 3H), 2.07 (t, J = 1 2.9 Hz, 2H), 1 .76 (d, J = 1 1 .9 Hz, 1H), 1 .52 (d, J = 12.1 Hz, 1 H), 1 .22 (t, J = 7.3 Hz, 3H)
EXAMPLE 4
Preparation of (2,6-difluorophenyl)(imino)(methyl)- 6-sulfanone Step A: Preparation of (2,6-difluorophenyl)(methyl)sulfane
To a stirred solution of 2,6-difluorobenzenethiol ( 1 g, 6.8 mmol) in water (30 mL), triethylamine ( 1.7 mL, 12.4 mmol) was added, lodomethane (0.7 mL, 1 1 .4 mmol) was then added to the reaction mixture and the reaction mixture was stirred at 30 °C for 16 h. After completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate. The ethyl acetate layer was concentrated and the residue was purified by column chromatography 100% ethyl acetate as an eluent to obtain (2,6- difluoiOphenyl)(methyl)sulfane ( 1 g, 6.2 mmol, 91 % yield).
Step B: Preparation of (2,6-difluorophenyl)(imino)(methyl)-X6-siiIfanone
To a stirred solution of (2,6-difluoiOphenyl)(methyl)sulfane ( 1 g, 6.2 mmol) in methanol (4 mL), ammonium carbamate ( 1 .0 g, 12.5 mmol), iodobenzene diacetate (5.0 g, 15.6 mmol) were added consecutively at 0 °C. The reaction mixture was stirred at 25 °C for 5 h. The reaction mixture was diluted with ice-water ( 10 mL) and methanol was evaporated. The resulting residue was extracted twice with ethyl acetate (20 mL). The ethyl acetate layer was washed with brine (20 mL), dried over anhydrous sodium sulphate and evaporated. The residue was further purified by column chromatography using 100% ethyl acetate to obtain (2,6-difluorophenyl)(imino)(iTiethyl)'- 6-SLilfanone ( 0.7 g, 3.7 mmol, 59% yield). EXAMPLE 5
Preparation of (2,6-dimethylphenyl)(ethyl)(imino)- 6-sulfanone
Step A: Preparation of (2,6-dimethyIphenyI)(ethyl)sulfane To a stirred solution of 2,6-dimethylbenzenethiol ( 1 .0 g, 7.2 mmol) in water (5 mL), triethylamine ( 1 .0 mL, 7.2 mmol), 2,6-dimethylbenzenethiol ( 1 .0 g, 7.2 mmol) were added. The resulting reaction mixture was stirred for 4 h at 25 "C. The reaction mixture was quenched slowly with ammonium chloride solution. The aqeous layer was extracted thrice with ethyl acetate (20 mL), ethyl acetate was evaporated and the residue was purified by column chromatography using 100% ethyl acetate to obtain (2,6- dimethylphenyl)(ethyl)sulfane (0.2 g, 1.2 mmol, 17% yield).
Step B: Preparation of (2,6-dimethylphenyl)(ethyl)(imino)- 6-suIfanone
To a stirred solution of (2,6-dimethylphenyl)(ethyl)sulfane ( 1 g, 6.0 mmol) in methanol (4 mL) ammonium carbamate (0.9 g, 12.0 mmol) and iodobenzene diacetate (4.0 g, 12.0 mmol) were added consecutively at 0 °C. The resulting reaction mixture was stirred at 25 °C for 12 h. The reaction mixture was diluted with ice-water ( 10 mL) and methanol was evaporated. The residue was extracted twice with ethyl acetate (20 mL). The ethyl acetate layer was washed with brine (20 mL), dried over sodium sulphate concentrated under reduced pressure and purified using column chromatography using 100% ethyl acetate as an eluent to obtain (2,6-dimethylphenyl)(ethyl)(imino)^6-sulfanone ( 1 g, 5.07 mmol, 84 % yield). EXAMPLE 6
Preparation of (3-bromophenyl) (methyl) (((2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl) acetyl) piperidin-4-yl) thiazol-4-yl) methyl) imino)^6-sulfanone (Compound 77)
Step A: Preparation of tert-butyl 4-(4-(bromomethyl)thiazol-2-yl)piperidine-l-carboxyIate
To a solution of tert-butyl 4-(4-(hydroxymethyl)thiazol-2-yl)piperidine- l -carboxylate (3.2 g, 10.7 mmol) in dichioromethane ( 100 mL) at 0 °C, phosphorus tribromide (0.7 mL, 7.5 mmol) was added dropwise and the reaction mixture was stirred for 4 h at 0 °C. The reaction mixture was quenched with sodium bicarbonate solution (250 mL) and extracted twice with dichioromethane (250 mL). The combined dichlormethane layer was dried over anhydrous sodium sulphate, filtered, concentrated, and purified by column chromatography usi;ng 10% ethyl acetate and hexane as an eluent to obtain tert-butyl 4-(4- (bromomethyl)thiazol-2-yl)piperidine- l -carboxylate ( 1 .6 g, 4.43 mmol, 41 % yield)
Ή-NMR (400 MHz, DMSO-c/6) δ 7.22 (s, 1 H), 4.58 (d, J = 0.5 Hz, 2H), 4.1 2-4.39 (m, 21 1), 3.1 9 (tt, J = 1 1 .7, 3.8 Hz, 1 11), 2.89 (t, J = 12.3 Hz, 2H), 2.03-2.14 (m, 2H), 1.68- 1 .83 (m, 2H), 1 .46- 1 .49 (m, 9H). MS: m/z = 361 [M+l ].
Step B: Preparation of tert-butyl 4-(4-((((3-bromophenyl)(methy])(oxo)- 6- sulfaneylidene)amino)methyl)thiazol-2-yl)piperidine-l-carboxyIate To a solution of tert-butyl 4-(4-(bromomethyl)thiazol-2-yl)piperidine- l -carboxylate (0.71 g, 2 mmol), 3- bromophenyl)(imino)(methyl)- 6-sulfanone (0.47g, 2 mmol) in dimethylformamide (20 mL) at 0 °C, potassium tert-butoxide (0.34 g, 3 mmol) was added portion wise over 2 min. The resulting reaction mixture was stirred at 0 °C for 2 h. The reaction mixture was quenched with ice ( 10 g) and poured into a mixture of ethyl acetate (200 mL) and water ( 1 50 mL). Ethyl acetate and water layers were separated and the aqueous layer was extracted thrice with ethyl acetate (200 mL). The combined ethyl acetate layer was dried over anhydrous sodium sulphate, filtered, and concentrated. The residue was purified by column chromatography using 20 % ethyl acetate in hexane as an eluent to obtain tert-butyl 4-(4-((((3- bromophenyl)(methyl)(oxo)-λ6-sulfaneylidene)amino)methyl)thiazol-2-yl)pipe idine- l -cal·bo ylate (0.9 g, 89% yield).
Ή-NMR (400 MHz, CHLOROFORM-rf) δ 7.74-8.20 (m, 2H), 7.43-7.54 (m, 1 H), 7.1 1 (s, 1 H), 5.32 (s, 2H), 4.12-4.31 (m, 2H), 2.84-3.19 (m, 2H), 2.07-2. 13 (in, 2H), 1.64-1.77 (m, 2H), 1.21 -1.49 (m, 1H), 1 .39 (s, 9H). MS: m/z = 414 [M+l ].
Step C: Preparation of (3-bromophenyl)(methyl)(((2-(piperidin-4-yl)thiazol-4-yl)methyl)imino)- 6- sulfanone
To a solution of tert-butyl 4-(4-((((3-biOmophenyl)(methyi)(oxo)- 6-sulfanylidene)amino)methyl) thiazol- 2-yl) piperidine- l -carboxylate ( l .Og, 2 mmol) in dichloromethane (50 mL) was added trifluoroacetic acid (4.3 ml, 58.3 mmol). The reaction mixture was stirred at 25 °C for 1 h and concentrated to obtain (3- bromophenyl)(methyl)(((2-(piperidin-4-yl)thiazol-4-yl)methyl)imino)- 6-sulfanone(0.7g, 97% yield). MS: m/z = 416.10 [M+3].
Step E: Preparation of (3-bromophenyJ)(met yl)(((2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazol-4-yI)methyl)imino)-X6-sulfanone
To a solution of (3-bromophenyl) (methyl)(((2-(piperidin-4-yl) thiazol-4-yl) methyl)imino)^6-sulfanone ; (362 mg, 0.9 mmol) in N, N-dimethylformamide (8 ml), N, N-diisopropylethylamine (0. 18 mi, 1.1 mmol) was added at 25 °C. The resulting reaction mixture was stirred for 10 min, then (HATU (498 mg, 1.3 mmol) and 2-(5-methyl-3-(trifluoromethyl)- l H-pyrazoI- l -yl)acetic acid (200 mg, 1 .0 mmol) were added and stirred at 25 °C for l h. The reaction was quenched with water ( 10 mL) then extracted twice with ethyl acetate ( 15mL), combined ethyl acetate layer was washed with brine ( 10 mL) and dried over sodium sulphate, concentrated and purified by preparative HPLC to obtain (3-bromophenyl)(methyl)(((2-( l -(2-(5- methyl-3-(trifluoromethyl)- l H-pyrazol- l -yI)acetyl)piperidin-4-yl)thiazol-4-yl)methyl)imino)- 6- sulfanone ( 170 mg, 0.3 mmol, 32 % yield). EXAMPLE 7
Preparation of l-(2-(l-(2-(3, 5-bis (difluoromethyl)-lH-pyrazol-l-yl) acetyl) piperidin-4-yl) thiazol- 4-yl)-3-((4-bromophenyl) (methyl) (oxo)^6-suIfanylidene) urea (Compound 139)
Step A: Preparation of tert-butyl 4-(4-(3-((4-bromophenyl) (methyl) (oxo)- 6-sulfanylidene) ureido) thiazol-2-yl) piperidine-l-carboxylate
To a solution of 2-( l -(tert-butoxycarbonyl) piperidin-4-yl) thiazole-4-carboxylic acid ( 1 g, 3.2 mmol) in acetonitrile (20 mL), triethylamine ( 1 .3 mL, 9.6 mmol) and diphenylphosphoryl azide ( 1 . 1 niL, 4.8 mmol) were added. The resulting reaction mixture was stirred at 25 °C for 16 h. The reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate ( 100 mL). The ethyl acetate layer was dried over anhydrous sodium sulphate and concentrated to obtain tert-butyl 4-(4-(azidocarbonyl) thiazol-2-yl) piperidine-l -carboxylate. tert-butyl 4-(4-(azidocarbonyl)thiazol-2-yl)piperidine- l -carboxylate and (4- bromophenyl)(imino)(methyl)^6-sulfanone (0.7 g, 3.2 mmol) were taken up in acetonitrile (20 mL) and heated to 90 °C for 1 6 h. The resulting reaction mixture was concentrated under reduced pressure and purified by column chromatography using 50% ethyl acetate in hexane as an eluent to obtain tert-butyl 4- (4-(3-((4-blΌlTlophenyl)(methyl)(oxo)-λ6-sulfanylidene)ureido)thiazol-2-yl)piperidine- l -carboxylate ( 1 .4 g, 2.6 mmol, 80% yield).
MS: m/z = 545.05 [M+3].
Step B: Preparation of l-((4-bromophenyl) (methyl) (oxo)^6-sulfanylidene)-3-(2-(piperidin-4-yl) thiazol-4-yl) urea 2, 2, 2-trifluoroacetate To a solution of tert-butyl 4-(4-(3-((4-bromophenyl) (methyl) (oxo)- 6-sulfanylidene) ureido) thiazol-2- yl) piperidine- l -carboxylate ( 1 g, 1.8 mmol) in dichloromethane ( 10 mL), was added trifluoroacetic acid (4.2 mL, 55 mmol). The resulting reaction mixture was stirred at 25 °C for 2 h. The reaction mixture was concentrated to obtain l -((4-bromophenyl) (methyl) (oxo)- 6-suIfanylidene)-3-(2-(piperidin-4-yi) thiazol- 4-yl) urea 2, 2, 2-trifluoroacetate ( 1 g, 1 .8 mmol, 98% yield). MS: m/z = 445. 1
Step C: l-(2-(l -(2-(3, 5-bis (difluoromethyl)-lH-pyrazol-l-yl) acetyl) piperidin-4-yl) thiazoI-4-yl)-3- ((4-bromophenyl) (methyl) (oxo)- '-sulfanylidene) urea
To a solution of 1 -((4-bromophenyl)(methyl)(oxo)- 6-sulfanyl idene)-3-(2-(piperidin-4-yl)thiazol-4- yl)urea (0.3 g, 0.7 mmol) in N,N-dimethylformamide (5 mL), N,N-diisopropyIethylamine (0.3 mL, 2 mmol), 2-(3,5-bis(difluoromethyl)-lH-pyrazol-l-yl)acetic acid (0.15 g, 0.7 mmol) and HATU (0.3 g, 0.8 mmol) were added successively. The resulting reaction mixture was stirred at 25 °C for 2 h. The reaction mixture was diluted with cold water (50 mL) and extracted twice with ethyl acetate (50 mL). The ethyl acetate layer was washed twice with cold water (50 mL), dried over anhydrous sodium sulphate and 5 concentrated under reduced pressure. The product was purified by column chromatography using 100% ethyl acetate as an eluent to obtain l-(2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin- 4-yl)thiazol-4-yl)-3-((4-bi mophenyl)(methyl)(oxo)- 6-sulfanylidene)urea (200 mg, 0.3 mmol, 45% yield).
Ή- MR (400 MHz, DMSO- δ 10.14 (s, 1H), 7.88-7.93 (m, 4H), 6.89-7.31 (m, 4H), 5.38 (dd,./= 37.0, 0 17.0 Hz, 2H), 4.32 (d, J= 13.4 Hz, 1H), 3.94 (d, ./= 14.2 Hz, 1H), 3.47 (s, 3H), 3.19-3.26 (m, 2H), 2.72- 2.88 (m, 1H), 2.05 (d, J= 11.7 Hz, 2H), 1.70 (m, 1H), 1.49 (m 1H)
MS: m/z = 653.05 [M+3].
The compounds listed in Table No.1 are prepared analogously to the processes described in the example 1 to 7 using appropriate starting material. 5 Table No.1:
Figure imgf000069_0001
2.04-2.11 (m, 2H), 1.72-1.81 (m, IH), 1.53 (dd, J =
26.1, 14.2 Hz, IH)
2-(l -(2-(3,5-dimethyI-l H-pyrazol-1 - 1 H-NMR (400 MHz, DMSO-i/6) δ 8.22 (s, IH), 7.55 (d, 514.25 yl)acetyl)piperidin-4-yl)-N-((2,6- J = 13.0 Hz, OH), 7.43 (t, J = 7.6 Hz, IH), 7.27 (d, J = dimethylphenyl)(methyl)(oxo)- 6- 7.6 Hz, 2H), 5.79 (d, J = 9.3 Hz, IH), 4.89-5.02 (m, 2H),
sulfaneylidene)thiazole-4- 4.35 (d, J = 13.0 Hz, IH), 3.99 (d, J = 14.5 Hz, IH),
carboxamide 3.55 (s, 3H), 3.34 (d, J = 3.8 Hz, IH), 3.28 (d, J = 3.4
Hz, OH), 3.20 (t, J = 11.8 Hz, IH), 2.74-2.80 (m, IH),
2.64-2.68 (m, 6H), 2.02-2.09 (m, 9H), 1.66-1.69 (m,
IH), 1.48-1.51 (m, IH), 1.23-1.27 (m, IH), 1.08-1.15
(m, 2H), 0.81-0.87 (m, IH)
2-( 1 -(2-(3-bromo-2-oxo-5- 1 H-NMR (400 MHz, DMSO-i/6) δ 8.39 (d, J = 1.2 Hz, 658.85 (trifl uoromethy 1 )pyri di n- 1 (2H)- IH), 8.29 (d, J = 2.4 Hz, IH), 8.23 (s, IH), 7.43 (t, J = yl)acetyl)piperidin-4-yl)-N-((2,6- 7.6 Hz, IH), 7.27 (d, J = 7.6 Hz, 2H), 4.99 (dd, J = 21.7, dimethylphenyl)(methyl)(oxo)- 6- 15.7 Hz, 2H), 4.33 (d, J = 13.3 Hz, IH), 3.96 (d, J =
sulfaneylidene)thiazole-4- 13.9 Hz, IH), 3.55 (s, 3H), 3.34-3.39 (m, IH), 3.23-3.27
carboxamide (m, IH), 2.79-2.85 (m, IH), 2.60-2.68 (m, 6H), 2.04- 2.13 (m, 2H), 1.76 (d, J = 12.1 Hz, 1 H), 1.53 (d, J = 12.5
Hz, IH), 1.09-1.23 (m, IH)
2-( 1 -(2-(3-chloro-2-oxo-5- 1 H-NMR (400 MHz, DMSO-a ) δ 8.36 (t, J = 1.1 Hz, 615.10 (trifluoromethyl )pyri di n- 1 (2H)- IH), 8.23 (s, IH), 8.16 (d, J = 2.4 Hz, IH), 7.43 (t, J = yl)acetyl)piperidin-4-yl)-N-((2,6- 7.6 Hz, IH), 7.27 (d, J = 7.6 Hz, 2H), 4.99 (dd, J = 21.5, dimethylphenyI)(rnethyl)(oxo)- 6- 15.7 Hz, 2H), 4.34 (d, J = 13.3 Hz, IH), 3.96 (d, J =
sul faneyl idene)thi azole-4- 13.4 Hz, IH), 3.57 (d, J = 15.0 Hz, 3H), 3.33-3.39 (m,
carboxamide IH), 3.24-3.27 (m, IH), 2.79-2.86 (m, IH), 2.64 (t, J =
15.0 Hz, 6H), 2.04-2.13 (m, 2H), 1.77 (d, J = 11.5 Hz,
IH), 1.51-1.57 (m, IH), 1.21-1.25 (m, IH), 0.81-0.87
(m, IH)
N-((2,6- 'H-NMR (400 MHz, DMSO-i6) δ 8.21 (s, IH), 7.55- 564.15 dimethylphenyl)(methyl)(oxo)- 6- 7.59 (m, 2H), 7.52-7.53 (m, 2H), 7.43 (t, J = 7.6 Hz,
sulfaneylidene)-2-(l-(2-(3- IH), 7.26 (d, J = 7.6 Hz, 2H), 4.42 (d, J = 13.0 Hz, IH),
(trifluoromethyl)phenyl)acetyl)piperi 4.05 (d, J = 13.3 Hz, IH), 3.87 (s, 2H), 3.54 (s, 3H),
din-4-yl)thiazole-4-carboxamide 3.25-3.29 (m, IH), 3.15-3.21 (m, IH), 2.72-2.78 (m,
IH), 2.63-2.67 (m, 6H), 2.02 (d, J = 12.4 Hz, 2H), 1.50
(q, J= 11.6 Hz, 2H)
2-(l-(2-(3,5-bis(difluoromethyl)-lH- 'H-NMR (400 MHz, DMSO-aK) δ 8.25 (s, IH), 7.44 (t, 600.05 pyrazol - 1 -yl)acety l)pi peri di n-4-y 1 )- J = 7.6 Hz, IH), 7.26-7.30 (m, 2H), 7.16 (dd, J = 7.3, 4.4
N-((2,6- Hz, IH), 7.01-7.04 (m, IH), 6.87-6.89 (m,' IH), 5.38 (q, dimethylphenyl)(ethyl)(oxo)- 6- J = 17.1 Hz, 211), 4.32 (d, J = 13.1 Hz, IH), 3.94 (d, J =
sulfaneylidene)thiazole-4- 13.8 Hz, IH), 3.56-3.71 (m, 2H), 3.35 (q, J = 3.8 Hz,
carboxamide IH), 3.30 (s, OH), 3.21-3.27 (m, IH), 2.78-2.84 (m, IH),
2.59-2.66 (m, 6H), 2.03-2.10 (m, 2H), 1.75 (d, J = 11.9
Hz, 1 H), 1.52 (d, J = 11.9 Hz, 1 H), 1.22 (t, J = 7.3 Hz,
3H), 1.15 (t, J = 6.3 Hz, IH) 2-(l-(2-(3,5-dimethyl-lH-pyrazol-l- 'H-NMR (400 MHz, OMSO-d6) δ 8.25 (s, IH), 7.44 (t, 528.60 yl)acetyl)piperidin-4-yl)-N-((2,6- J = 7.6 Hz, IH), 7.27 (d, J = 7.6 Hz, 2H), 5.78 (s, IH), dimethylphenyl)(ethyI)(oxo)- 6- 4.96 (dd, J = 35.8, 16.7 Hz, 2H), 4.35 (d, J = 13.4 Hz,
sulfaneylidene)thiazole-4- IH), 3.98 (d, J = 13.6 Hz, IH), 3.62 (dq, J = 30.2, 7.3
carboxamide Hz, 2H), 3.27-3.31 (m, IH), 3.17-3.23 (m, IH), 2.77 (t, J
= 11.5 Hz, IH), 2.62-2.66 (m, 6H), 2.04-2.08 (m, 8H),
1.67 (d, J = 12.2 Hz, IH), 1.49 (d, J = 11.9 Hz, IH),
1.20-1.27 (m, 4H)
2-(l-(2-(3-chloro-2-oxo-5- 1 H-NMR (400 MHz, DMSO-i¾) δ 8.36 (d, J = 1.1 Hz, 629.10 (tri fl uoromet hy 1 )pyri d i n- 1 (2H)- IH), 8.26 (s, IH), 8.16 (d, J = 2.4 Hz, IH), 7.44 (t, J = yl)acetyl)piperidin-4-yl)-N-((2,6- 7.6 Hz, IH), 7.27 (d, J = 7.5 Hz, 2H), 5.75 (s, OH), 4.99 dimethylphenyl)(ethyl)(oxo)^6- (dd, J = 22.3, 15.9 Hz, 2H), 4.33 (d, J = 13.1 Hz, IH),
sulfaneylidene)thiazole-4- 3.96 (d, J = 13.6 Hz, IH), 3.54-3.69 (m, 2H), 3.36 (td, J
carboxamide = 7.7, 3.9 Hz, IH), 3.24-3.28 (m, IH), 2.80-2.85 (m,
IH), 2.59-2.66 (m, 6H), 2.04-2.13 (m, 2H), 1.72-1.81
(m, IH), 1.48-1.57 (m, IH), 1.38 (s, OH), 1.21-1.26 (m,
4H), 0.93 (d, J = 6.7 Hz, OH), 0.80-0.86 (m, IH)
N-((2,6- 'H-NMR (400 MHz, DMSO-i/6) δ 8.24 (s, IH), 7.52- 578.50 dimethylphenyl)(ethyl)(oxo)- 6- 7.59 (4H), 7.44 (t, J = 7.6 Hz, IH), 7.27 (d, J = 7.6 Hz,
sulfaneylidene)-2-(l -(2-(3- 2H), 4.42 (d, J = 13.9 Hz, IH), 4.05 (d, J = 13.2 Hz,
(tri fl uoromethy 1 )phenyl )acety 1 )piperi IH), 3.87 (s, 2H), 3.53-3.70 (m, 2H), 3.26-3.30 (m, IH),
din-4-yl)thiazole-4-carboxamide 3.18 (t, J = 11.6 Hz, IH), 2.75 (t, J = 11.6 Hz, IH), 2.62
(s, 6H), 2.02 (d, J = 12.5 Hz, 2H), 1.43-1.58 (m, 2H),
1.22 (t, J = 7.3 Hz, 3H)
2-( 1 -(2-(3-bromo-2-oxo-5- 'H-NMR (400 MHz, DMSO-J6) δ 8.40 (s, IH), 8.31 (d, 672.95 (trifluoromethyi)pyridin-l(2H)- J = 2.2 Hz, IH), 8.27 (s, IH), 7.45 (t, J = 7.6 Hz, IH),
yl)acetyl)piperidin-4-yl)-N-((2,6- 7.29 (d, J = 7.6 Hz, 2H), 5.01 (dd, J = 22.3, 15.9 Hz,
dimethylphenyl)(ethyl)(oxo)- 6- 2H), 4.35 (d, J = 13.2 Hz, IH), 3.97 (d, J = 13.4 Hz,
sulfaneylidene)thiazole-4- IH), 3.56-3.73 (m, 2H), 3.35-3.40 (m, IH), 3.28 (t, J =
carboxamide 12.3 Hz, IH), 2.84 (t, J = 11.6 Hz, IH), 2.64 (s, 6H),
2.06-2.15 (m, 2H), 1.78 (dd, J = 23.6, 12.3 Hz, IH),
1.54 (dd, J = 24.4, 12.2 Hz, IH), ), 1.24 (t, J = 7.2 Hz,
3H).
2-(l-(2-(3,5-bis(difluoromethyl)-lH- 'H-NMR (400 MHz, DMSO-otf) δ 8.26 (s, IH), 7.78- 594.10 pyrazol-l-yl)acetyl)piperidin-4-yl)- 7.85 (m, IH), 7.34-7.39 (m, 2H), 6.49 (s, IH), 5.27 (dd,
N-((2,6- J = 36.8, 17.0 Hz, 2H), 4.36 (d, J = 14.4 Hz, IH), 3.95 difluorophenyl)(methyl)(oxo)- 6- (d, J = 13.7; Hz, IH), 3.70 (s, 3H), 3.36 (t, J = 3.8 Hz,
sulfaneylidene)thiazole-4- IH), 3.20-3.27 (m, IH), 2.80 (t, J = 11.6 Hz, IH), 2.19
carboxamide (s, 3H), 2.04-2.10 (m, 2H), 1.76 (dd, J = 27.6, 11.5 Hz,
IH), 1.52 (dd, J = 24.4, 12.2 Hz, IH)
N-((3-bromophenyl)(methyl)(oxo)- 'H-NMR (400 MHz, DMSO-c/6) δ 8.29 (s, IH), 8.19 (t, 566.00 6-sulfaneylidene)-2-( 1 -(2-(3,5- J = 1.8 Hz, IH), 8.01 (dd, J = 18.1, 8.0 Hz, 2H), 7.66 (t,
dimethyi-1 H-pyrazol-1 - J = 7.9 Hz, IH), 5.79 (s, IH), 4.98 (dd, J = 34.4, 16.7 yl)acetyl)piperidin-4-yI)thiazole-4- Hz, 2H), 4.37 (d, J = 12.7 Hz, IH), 4.01 (d, J = 13.4 Hz,
carboxamide IH), 3.66 (s, 3H), 3.36-3.37 (m, IH), 3.22 (t, J = 11.9
Hz, IH), 2.67-2.82 (m, IH), 2.06-2.10 (m, 8H), 1.72 (t, J
Figure imgf000072_0001
Figure imgf000073_0001
Figure imgf000074_0001
Figure imgf000075_0001
Figure imgf000076_0001
Figure imgf000077_0001
Figure imgf000078_0001
Figure imgf000079_0001
Figure imgf000080_0001
Figure imgf000081_0001
Figure imgf000082_0001
Figure imgf000083_0001
Figure imgf000084_0001
Figure imgf000085_0001
Figure imgf000086_0001
Figure imgf000087_0001
yl)acetyl)piperidin-4-yl)thiazole-4- 1 H), 3.72 (s, 3H), 3.37 (td, J= 7.6, 3.7 Hz, IH), 3.26 (t,
carboxamide J= 11.7 Hz, IH), 2.80-2.90 (m, 1 H), 2.20 (s, 3H), 2.06- 2.12 (m, 2H), 1.80 (t, J= 11.9 Hz, IH), 1.50-1.60(m,
IH)
2-(l-(2-(3,5-bis(difluoromethyl)-lH- Ή-NMR (400 MHz, DMSO-o½) δ 8.28 (s, IH), 8.01- 570.15(M' pyrazol-l-yl)acetyl)piperidin-4-yl)- 8.04 (m, 2H), 7.77 (dd, J = 6.8, 2.0 Hz, 2H), 6.88-7.30 1) N-((4-chIorophenyl)(methyl)(oxo)- (m, 3H), 5.38 (q,J= 17.0 Hz, 2H), 4.34 (d, J= 11.7 Hz,
121
X6-sulfaneylidene)thiazole-4- IH), 3.95 (d, J= 13.9 Hz, IH), 3.61 (s, 3H), 2.81 (t, J =
carboxamide 11.5 Hz, 2H), 2.04-2.11 (m, 3H), 1.76 (d, J= 9.8 Hz,
IH), 1.53(dd,J= 12.3, 4.3 Hz, IH)
N-(methyl(4-nitrophenyl)(oxo)- 6- 'H-NMR (400 MHz, OMSO-d6) δ 8.49 (dt, J= 9.4, 2.3 585.15 sulfanylidene)-2-( 1 -(2-(5-methyl-3- Hz, 2H), 8.28-8.33 (m, 3H), 6.50 (s, IH), 5.33 (d, J =
(trifluoromethyl)-lH-pyrazol-l- 16.9 Hz, IH), 5.24 (d,J= 16.9 Hz, IH), 4.38 (d, J =
122 yl)acetyl)piperidin-4-yl)thiazole-4- 13.4 Hz, IH), 3.97 (d,J = 13.4 Hz, IH), 3.70 (s, 3H),
carboxamide 3.37 (td, J =7.7, 3.7 Hz, IH), 3.26 (t, J= 11.7 Hz, IH),
2.80-2.85 (m, IH), 2.22 (d,J= 8.1 Hz, 3H), 2.06-2.12
(m, 2H), 1.74-1.83 (m, IH), 1.54 (t, 7= 11.5 Hz, IH)
2-(l-(2-(3,5-bis(difluoromethyl)-lH- 'H-NMR (400 MHz, DMSO- 6) δ 8.33 (s, IH), 7.92 (t, 594.10 pyrazol-l-yl)acetyl)piperidin-4-yl)- J= 9.2 Hz, 4H), 7.18 (d, J = 4.4 Hz, IH), 7.04 (d, J =
N-((4- 5.4 Hz, IH), 6.91 (d, ,7 = 4.2 Hz, IH), 5.44 (d,J= 17.1
bromophenyl)(isopentyl)(oxo)- 6- Hz, IH), 5.36 (d, J= 17.1 Hz, IH), 4.35 (d, J= 13.4 Hz,
123 sulfanylidene)thiazole-4- IH), 3.97 (d, J= 13.7 Hz, IH), 3.67-3.80 (m, 2H), 3.37
carboxamide (td, J= 7.7, 3.8 Hz, IH), 3.23-3.29 (m, IH), 2.80-2.86
(m, IH), 2.09 (t, J = 13.6 Hz, 2H), 1.80 (t, J= 11.7 Hz,
IH), 1.52-1.66 (m, 3H), 1.38 (dt, J= 17.9, 6.4 Hz, IH),
0.85 (dd, .7 = 6.5, 3.8 Hz, 6H)
N-((4- 'H-NMR (400 MHz, DMSO-^6) δ 8.33 (s, IH), 7.92 (t, 676.10 bromophenyl)(isopentyl)(oxo)- 6- J= 9.0 Hz, 4H), 6.50 (s, 1H.5.44 (d, .7= 17.1 Hz, IH),
sulfanylidene)-2-(l-(2-(5-methyl-3- 5.36 (d, .7= 17.1 Hz, IH) 4.38 (d, .7= 13.2 Hz, IH), 3.97
(tri fl uoromethy 1 )- 1 H -py razol - 1 - (d, J= 13.4 Hz, IH), 3.67-3.80 (m, 2H), 3.35-3.39 (m,
124
yl)acetyl)piperidin-4-yl)thiazole-4- IH), 3.26 (t, .7= 11.6Hz, IH), 2.83 (t, .7=11.6 Hz, IH),
carboxamide 2.21 (s, 3H), 2.09 (dd,J= 13.1, 11.6 Hz, 2H), 1.80 (t, J
= 11.7 Hz, IH), 1.52-1.68 (m, 3H), 1.34-1.43 (m, IH),
0.85 (dd, J = 6.6, 3.9 Hz, 6H)
2-( 1 -(2-(3,5-bis(difluoromethyl)- 1 H- 'H-NMR (400 MHz, DMSO-i¾) <58.25 (s, IH), 7.49- 606.15 pyrazol-l-yl)acetyl)piperidin-4-yl)- 7.59 (m, 2H), 7.45-7.49 (m, IH), 7.18 (d, J= 2.4 Hz,
N-((2-chloro-6- IH), 7.04 (d, .7= 3.7 Hz, IH), 6.91 (d, J=3.2Hz, IH), methylphenyl)(methyl)(oxo)- 6- 5.44 (d, .7 = 17.1 Hz, IH), 5.35 (d, .7= 17.1 Hz, IH),
125
sulfanylidene)thiazole-4- 4.34 (d, J= 12.7 Hz, 1H),!3.96 (d, J= 13.2 Hz, IH),
carboxamide 3.71 (s, 3H), 3.37 (s, IH), 3.22-3.30 (m, IH), 2.79-2.85
(m, IH), 2.75 (s, 3H), 2.04-2.11 (m, 2H), 1.77 (d,J =
12.0 Hz, IH), 1.54 (d,J= 12.2 Hz, IH)
1 -(2-( 1 -(2-(3,5-bis(difluoromethyl)- 'H-NMR (400 MHz, OMSO-d6) δ 10.15 (s, IH), 8.18 (t, 653.05 1 H-pyrazol-1 -yl)acetyl)piperidin-4- .7= 1.7 Hz, IH), 7.93-8.01 (m, 2H), 7.63 (t,.7=8.1 Hz,
yl)thiazol-4-yl)-3-((3- IH), 6.88-7.30 (m, 4H), 5.37 (dd,J=36.7, 17.1 Hz,
126
bromophenyl)(methyl)(oxo)- 6- 2H), 3.92-4.01 (m, IH), 3.52 (s, 3H), 3.18-3.26 (m, 2H),
sulfaneylidene)urea 2.78-2.83 (m, IH), 2.00-2.06 (m, 2H), 1.71 (td, .7= 12.0,
8.6 Hz, IH), 1.46-1.55 (m, IH) l-((3-bromophenyl)(methyl)(oxo)- 'H-NMR (400 MHz, DMSO- d) δ 10.12 (s, 1 H), 8.17 (t, 635.05 6-su!faneylidene)-3-(2-(l-(2-(5- J= 1.8 Hz, IH), 7.92-8.00 (m, 2H), 7.62 (t, ,/= 7.9 Hz, methyl-3-(trifluoromethyl)-l H- 1 H), 7.07 (s, 1 H), 6.48 (s, 1 H), 5.25 (dd, J = 38.3, 17.0
127 pyrazol-l-yl)acetyI)piperidin-4- Hz, 2H), 4.33 (d, J= 13.0 Hz, IH), 3.92-3.98 (m, IH),
yl)thiazol-4-yl)urea 3.51 (s, 3H), 3.18-3.26 (m, 2H), 2.76-2.82 (m, IH), 2.19
(s, 3H), 1.99-2.10 (m, 2H), 1.70 (m, IH), 1.49 (m, IH)
'H-NMR (400 MHz, OMSO-d6) δ 8.25 (s, IH), 7.53- 587.55
N-((2-chloro-6- 7.59 (m, 2H), 7.45-7.48 (m, IH), 6.50 (s, IH), 5.33 (d, J methylphenyl)(methyl)(oxo)- 6- = 17.1 Hz, IH), 5.24 (d, J = 16.9 Hz, IH), 4.36 (d, J =
128 sulfanylidene)-2-(l-(2-(5-methyl-3- 13.0 Hz, IH), 3.96 (d, J = 13.2 Hz, IH), 3.71 (s, 3H),
(trifl uoromethy 1 )- 1 H-pyrazol - 1 - 3.36-3.44 (m, IH), 3.22-3.31 (m, IH), 2.79-2.85 (m, yl)acetyl)piperidin-4-yl)thiazole-4- IH), 2.75 (s, 3H), 2.21 (s, 3H), 2.08 (t, J= 13.4 Hz, 2H),
carboxamide 1.79 (t, J= 12.3 Hz, IH), 1.51-1.59(m, IH)
2-(l-(2-(3,5-bis(difluoromethyl)-lH- 'H-NMR (400 MHz, DMSO-otf) δ 8.16 (t, J = 1.8 Hz, 639.05 pyrazol-l-yl)acetyl)piperidin-4-yl)- III), 8.00 (ddq, 7= 12.0, 8.0, 0.9 Hz, 2H), 7.66 (t, J =
129 N-((3-bromophenyl)(methyl)(oxo)- 8.4 Hz, 2H), 6.51 (s, IH), 5.32 (s, 2H), 3.62-3.66 (m,
6-sulfaneylidene)thiazole-4- 7H), 3.55 (d, J= 4.9 Hz, 2H), 3.43-3.45 (m, 2H), 2.22 carboxamide (s, 3H)
N-((3-bromophenyl)(methyl)(oxo)- 'H-NMR (400 MHz, DMSO-o½) δ 8.16 (t, J = 1.8 Hz, 620.90 6-sulfaneylidene)-2-(4-(2-(5- IH), 8.00 (ddq, J= 12.0, 8.0, 0.9 Hz, 2H), 7.66 (t, ./ =
130 methy 1 -3 -(tri fl uoromethy 1 )- 1 H- 8.4 Hz, 2H), 6.51 (s, IH), 5.32 (s, 2H), 3.62-3.66 (m,
pyrazo 1 - 1 -y 1 )acety 1 )piperazi n- 1 - 7H), 3.55 (d, J= 4.9 Hz, 2H), 3.43-3.45 (m, 2H), 2.22
yl)thiazole-4-carboxamide (s, 3H)
2-(4-(2-(3,5-bis(difluoromethyl)-lH- 'H-NMR (400 MHz, DMSO-i6) δ 7.88-7.93 (m, 4H), 639.05 pyrazol- 1 -yl)acetyl)piperazin- 1 -yl)- 7.65 (s, IH), 6.89-7.30 (m, 3H), 5.41 (s, 2H), 3.56-3.64
131 N-((4-bromophenyl)(methyl)(oxo)- (m, 7H), 3.52 (d, J = 4.6 Hz, 2H), 3.41 (t, J = 5.0 Hz,
6-sulfaneylidene)thiazole-4- 2H)
carboxamide
N-((4-bromophenyl)(methyl)(oxo)- 'H-NMR (400 MHz, DMSO-ί/ό δ 7.88-7.93 (m, 4H), 589 6-sulfaneylidene)-2-(4-(2-(3- 7.65 (s, IH), 7.54 (d, J= 1.7 Hz, IH), 7.13 (t, J= 53.7
132 (difluoromethyl)-l H-pyrazol-1- Hz, IH), 6.61 (d, J= 1.5 Hz, IH), 5.29 (d, J= 19.3 Hz,
yl)acetyl)piperazin-l-yl)thiazole-4- 2H), 3.56-3.65 (m, 7H), 3.50 (s, 2H), 3.41 (d, J = 4.4
carboxamide Hz, 2H)
N-((4-bromophenyl)(methyl)(oxo)- 'H-NMR (400 MHz, DMSO-i/6) δ 7.88-7.93 (m, 4H), 620.75 6-sulfaneylidene)-2-(4-(2-(5- 7.65 (s, IH), 6.50 (s, IH), 5.30 (s, 2H), 3.56-3.64 (m,
133 methyl-3-(trifluoromethyI)-lH- 7H), 3.52 (s, 2H), 3.41-3.43 (m, 2H), ,2.20-2.32 (m,
pyrazo 1 - 1 -y 1 )acety 1 )piperazi n- 1 - 3H),
yl)thiazole-4-carboxamide
'H-NMR (400 MHz, DMSO-i/6) δ 8.36 (s, IH), 7.86- 620.00
N-(methyl(oxo)(pyndin-2-yl)- 6-' 7.89 (m, 2H), 7.75-7.78 (m, 2H), 6.88-7.30 (m, 4H), sulfaneylidene)-2-(l-(2-(5-methyl-3- 5.38 (q, J = 17.1 Hz, 2H), 4.33 (d, ./ = 13.7 Hz, IH),
134
(trifl uoromethy i )- 1 H-pyrazol- 1 - 3.80-4.03 (m, IH), 3.33-3.37 (m, IH), 3.23 (d, J= 11.2 yl)acetyi)piperidin-4-yl)thiazole-4- Hz, 1 H), 2.81 (t, J = 11.6 Hz, 1 H), 2.07 (t, J = 13.9 Hz,
carboxamide 2H), 1.78 (s, IH), 1.53 (d,J= 15.2 Hz, IH), 1.37 (t,J =
6.7 Hz, 3H), 1.16 (t, J = 6.5 Hz, 3H)
3-(S-methyl-N-(2-(l-(2-(5-methyl-3- 'H-NMR (400 MHz, DMSCW6) δ 8.30 (s, IH), 8.06 634.1
(tri fl uoromethy 1 )- 1 H-pyrazol- 1 - (dq, J = 7.9, 1.0 Hz, 1 H), 8.02 (t, ,/ = 2.0 Hz, 1 H), 7.83
135 yl)acetyl)piperidin-4-yl)thiazole-4- (t, ,/ = 7.9 Hz, 1 H), 7.76 (dq, ./ = 8.2, 1.1 Hz, 1 H), 6.50
carbonyl)sulfonimidoyl)phenyl (s, IH), 5.33 (d, J = 17.1 Hz, IH), 5.24 (d, ./= 16.9 Hz,
methanesulfonate IH), 4.38 (d, J = 13.2 Hz, IH), 3.97 (d, J = 14.2 Hz,
Figure imgf000090_0001
Figure imgf000091_0001
Figure imgf000092_0001
Compound names generated by using ChemDraw Professional 16.0
BIOLOGY EXAMPLES:
Phytophthora infestans (Late blight of potato & tomato):
IN VITRO TEST: Compounds were dissolved in 0.3% DMSO & then added to Rye Agar medium just prior to dispensing it into petri dishes. 5 mL medium with compound in the desired concentration was dispensed into 60mm sterile petri-plates. After solidi fication each plate was seeded with 5mm size mycelial disc taken form periphery of actively growing virulent culture plate. Plates were incubated in growth chambers at 18 °C temperature and 95% relative humidity for seven days and radial growth was measured. Compounds 1 2 3 4 5 6 7 8 9 10
1 1 12 13 14 15 16 17 1 8 19 20 21 22
23 24 25 26 27 28 29 30 3 1 32 33 34
35 36 37 38 40 41 42 43 44 45 46 47
48 49 50 51 52 53 54 55 56 57 58 60
61 62 63 64 65 66 67 68 69 70 71 72
73 74 75 76 77 78 79 80 81 82 83 84
85 86 87 88 89 90 91 92 93 94 95 96
97 98 99 100 101 102 103 104 105 106 107 108
109 1 10 1 1 1 1 12 1 1 4 1 1 6 1 17 1 1 8 1 1 9 120 121 122
123 124 125 126 127 128 129 130 131 132 133 134
135 136 137 1 38 139 140 141 142 143 144 145 146
147 148 149 1 50 at 30 ppm gave 70% control in these tests when compared to the untreated check which showed extensive disease development.
GREENHOUSE: Compounds were dissolved in 2% DMSO/Acetone & then mixed with water to calibrated spray volume of 50 mL. This 50 mL spray solution was poured into the spray bottles for further applications. To test the preventive activity of compounds, healthy young Tomato plants raised in the greenhouse were sprayed with active compound preparation at the stated application rates inside the spray cabinets using hallow-cone nozzles. One day after treatment, the plants were inoculated with sporangial suspension (Cold sterile water) containing 0.24x 1 06 Phytophthora infestans inoculum. After inoculation the plants were kept in darkness at 1 5 °C during 24 hours, and then they were kept in greenhouse chamber at 1 8 °C temperature and 95-100 % relative humidity for disease expression. A visual assessment of compound 's performance was carried by rating the disease severity (0- 1 00% scale) on treated plants on 3, 7, 10 and 1 5 days after appl ication. Efficacy (% control) of the compounds was calculated by comparing the disease rating i n the treatment with untreated control. The sprayed plants were also assessed for compound's phytotoxic effects by recording symptoms like necrosis, chlorosis and stunting. Compounds
1 2 5 9 10 24 25 26 27 28 30 32 33
35 36 37 42 43 44 58 63 65 76 1 05 106
108 109 1 10 1 1 1 1 19 125 127 139 141 at 50 ppm gave 90% control in these tests when compared to the untreated check which showed extensive disease development. None of the compounds showed any negative crop response to any of the compounds tested.
Example B: Plasmopara viticola test in Grape
Compounds were dissolved in 2% DMSO/Acetone & then mixed with water to calibrated spray volume of 50 mL. This 50 mL spray solution was poured into the spray bottles for further applications.
To test the preventive activity of compounds, five week old healthy grape seedlings raised in the greenhouse were sprayed with active compound preparation at the stated application rates inside the spray cabinets using hallow-cone nozzles. One day after treatment, the plants were inoculated with inoculum suspension (Cold sterile water) containing 6x106 Plasmopara viticola inoculum. The inoculated plants were then kept in greenhouse chamber at 1 8-21 °C temperature and 95-100 % relative humidity for disease expression.
A visual assessment of compound's performance was carried by rating the disease severity (0-1 00% scale) on treated plants on 3, 7, 1 0 and 1 5 days after application. Efficacy (% control) of the compounds was calculated by comparing the disease rating in the treatment with untreated control. The sprayed plants were also assessed for compound's phytotoxic effects by recording symptoms like necrosis, chlorosis and stunting. Compounds 2 5 10 24 25 26 27 28 30 32
33 35 36 37 42 43 44 58 65 76 105 108
109 1 10 1 1 1 1 1 9 125 127 139 at 50 ppm gave 90% control in these tests when compared to the untreated check which showed extensive disease development. None of the compounds showed any negative crop response to any of the 'compounds tested.

Claims

WE CLAIM:
1 . A compound of Formula 1
Figure imgf000095_0001
5 wherein, E is a fragment selected from the group consisting of E-1 , E-2, E-3, E-4 and E-5 :
Figure imgf000095_0002
E- 1 E-2 E-3 E-4 E-5 wherein, T' , T2J3 and T4 are independently selected from 5- or 6- membered aryl ring or 5- or 6- membered saturated or partially saturated cyclic ring or 5- or 6- membered heteroaryl ring or 5- or 6- or 7- membered saturated or partially saturated heterocyclic ring, wherein each ring member0 of heteroaryl ring is selected from Q N, O and S, and wherein each ring member of heterocyclic ring is selected from C, N, 0, S(0)„ C(=0), C(=S), S(=NR2) and S(0)=NR2, and T1, T2 , T3 and T4 are optionally substituted by one or more R1 on C atoms and one or more R2 on hetero atoms; or
T2 T3 and T4 are independently selected from C rC6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C Q, haloalkyi, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C8 cycloalkyi, C3-C8 halocycloalkyl, CrC65 alkyl C3-C8 cycloalkyi, C3-C8 cycloalkyi CrC6 alkyl, C3-C8 cycloalkyi C3-C8 cycloalkyi, C3-C8 halocycloalkyl CrC6 alkyl, C ]-C6 alkoxy C rC6 alkyl, C3-C6 cycloalkoxy C C6 alkyl, CrC6 alkylthio C ]-C6 alkyl, Ci-C6 alkylsulfinyl C!-C6 alkyl, CrC6 alkylsuifonyl C i-C6 alkyl, Cj-C6 alkylamino C rC6 alkyl, C rC6 dialkylamino CrC6 alkyl, C rQ haloalkylamino C rCf) alkyl, C3-C3 cycloalkylamino CrC6 alkyl, CrC6 alkylcarbonyl, C rC6 haloalkylcarbonyl, C3-C80 cycloalkylcarbonyl, C|-C6 alkoxycarbonyl, C3-C8 cycloalkoxycarbonyl, CrC6 alkylaminocarbonyl, C C6 dialkylaminocarbonyl, C3-C8 cycloalkylaminocarbonyl, CrC6 haloalkoxy C rC6 alkyl, C rC6 hydroxyalkyl, CrQ, alkoxy, Q-Q haloalkoxy, C3-Q cycloalkoxy, C3-Q halocycloalkoxy, C3-C8 cycloalkyi Q-Q alkoxy, Q-Q alkenyloxy, Q-Q haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C rC alkoxy Q-Q alkoxy, Q -Q alkylcarbonyloxy, Q-5 C6 haloalkylcarbonyloxy, C3-C8 cycloalkylcarbonyloxy, Q-C6 alkylcarbonyl Q -Q alkoxy, Q-Q alkylthio, Q -Q haloalkylthio, C3-Q cycloalky!thio, C ,-C6 alkylsulfinyl, C!-C6 haloalkylsulfinyl, C ]-C6 alkylsulfonyl, C rC6 haloalkylsulfonyl, C3-C8 cycloalkylsulfonyl, C rC6 trialkylsilyl, CrC6 alkylsulfonylamino, and C rC6 haloalkylsulfonylamino;
L1 , L2 , L3 , L4, and L5 are independently a direct bond, O, S(=0)a, C(=0), C(=S), C(R22)2, C(R22)2- C(R22)2, or NR23; A is a direct bond or C(R4)2 or C(R4)2-C(R4)2, C(=0) or NR5;
W is O or S;
W' is OR18, SRl 9, N(R20)2 or R21 ;
a and m are independently 0, 1 or 2;
Z is C or N; R3 is selected from hydrogen, halogen, cyano, hydroxy, amino, aldehyde, carboxylic acid, C rC6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CrC6 haloalkyi, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C -C6 cycloalkyi, C3-C6 halocycloalkyl, CrC6 alkyl C3-C6 cycloalkyl, C3-C6 cycloalkyl C C6 alkyl, C3-C6 halocycloalkyl Ci-Ce alkyl, C3-C6 cycloalkenyl, C3-C6 halocycloalkenyl, CrC<, alkoxy C rC6 alkyl, CrC6 alkyl Ci-C6 thioalkyl, Q-Q, alkyl Ci-C6 sulfinylalkyl, C C6 alkyl C rC6 sulfonylalkyl, C C6 alkylamino CrC6 alkyl, CrC<; dialkylamino CrC6 alkyl, C,-C6 haloalkylamino C ,-C6 alkyl, C C6 alkylcarbonyl, CrC6 haloalkylcarbonyl, C3-C6 cycloalkylcarbonyl, CrC6 alkoxycarbonyl, C3-C6 cycloalkoxycarbonyl, C3-C6 cycloalkyl C C6 alkoxycarbonyl, CrC6 aikyiaminocarbonyl, CrC6 dialkylaminocarbonyl, CrC6 alkoxy, CrC6 haioaikoxy, C3-C6 cycloalkoxy, C3-C(, halocycloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C ]-C6 alkoxy C!-C6 alkoxy, CrC6 alkylcarbonyloxy, Ci-C6 haloalkylcarbonyloxy, C ,-C6 alkylthio, C,-C6 haloalkylthio, C3-C6 cycloalkylthio, C rC6 alkylamino, Cr C6 dialkylamino, CrC6 haloalkylamino, C C6 halodialkylamino, C3-C6 cycloalkylamino, CrC6 alkylcarbonylamino, C C6 haloalkylcarbonylamino, C| -C6 alkylsulfonylamino and C,-C6 haloalkylsulfonylamino; or two R3 are taken together as C rC6 alkyl, C C4 aikylene or C2-C4 aikenyiene to form a bridged bicyclic or fused bicyclic ring system; or two R3 attached to adjacent ring carbon atoms are taken together as -CH=CH-CH==CH- optionally substituted with a substituent selected from C rC4 alkyl, CrC4 haloalkyi, C,-C4 alkoxy, C rC4 haioaikoxy, halogen, hydroxy, amino, cyano and nitro;
the presentation " " in ring D is a single bond when Z is N and the presentation " " is a single or double bond when Z is C; "n" is an integer ranging from 0 to 9 with a proviso that when Z is N, "n" is an integer ranging from 0 to
8; and when the presentation " " in ring D is a double bond then "n" is an integer ranging from 0 to
7;
G is an optionally substituted 5- or 6- membered heteroaryl ring or 5- or 6-membered saturated or partially saturated heterocycl ic ring, each ring member of heteroaryl ring is selected from C, N, O and S, and wherein each ring member of heterocyclic ring is selected from C, N, O, S(0)a, C(=0), C(=S), S(=NR2) and S(0)=NR2;
wherein, the optional substituent on G is R3a on carbon ring members and Rl la on heteroatom ring members;
R½ is hydrogen or R3b; R b is phenyl, C rC3 alkyl, C |-C3 haloalkyl, halogen or 5- or 6-membered heteroaryl ring optionally substituted with one or more substituents independently selected from R4a on carbon ring members and R4b on heteroatom ring members;
R4a is independently selected from C,-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3- C6 cycloalkyl, C3-C6 cycloalkyl C C6 alkyl, C]-C6 alkyl C3-C6 cycloalkyl, C r C6 haloalkyl C3-C6 cycloalkyl, CrC6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-
C6 halocycloalkyl, halogen, hydroxy, amino, cyano, nitro, C i-C6 alkoxy, Cr C6 haloalkoxy, CrC6 alkylthio, C C6 alkylsulfinyl, CrC6 alkylsulfonyl, Cr C6 haloalkylthio, CrC6 haloalkylsulfinyl, C C6 haloalkylsulfonyl, C C6 alkylamino, C:- C6 dialkylamino, C3-C6 cycloalkylamino, C C6 alkoxy CrC6 alkyl, CrC6 hydroxyalkyl, C ,-C6 alkylcarbonyl, CrCf, alkoxycarbonyl, CrC(, alkylcarbonyloxy, C r
C6 alkylcarbonylthio, C C6 alkylaminocarbonyl, C |-C6 dialkylaminocarbonyl and C r C6 trialkylsilyl;
R4b is independently selected from C ,-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3- C6 cycloalkyl, C rC6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3- C6 halocycloalkyl and C ,-C6 alkoxy CrC6 alkyl;
R "a is hydrogen or R l lb; R l l b is independently C,-C3 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3- C6 cycloalkyl, C rC6 haloalkyl, C2-C6 haloalkenyl, C2-C(, haloalkynyl, C3-C6 halocycloalkyl and C ]-C6 alkoxy C rC6 alkyl;
J is selected from fragments of Formula II and III
Figure imgf000097_0001
wherein, the right side of the fragment of Formula II or III is attached to Q and the left side of the fragment of Formula II or III is attached to G;
L6 and L7 are independently a direct bond, O, C(=0), C(=S), C(RI2)2, C(RI 2)2-C(R 12)2, NR 13 or NR, 3C(=0); or
L6 and L7 together with the atoms to which they are attached may form a 4- to 7- membered carbocyclic or heterocyclic ring or ring system; or
R" together with L6 or L7 or G or Q or R12 or R13 or R14 or Ri 5 may form a 4- to 7- membered carbocyclic or heterocyclic ring or ring system;
Q is independently phenyl, benzyl, naphthalenyl, a 5- or 6- membered aryl ring, an 8- to 1 1 - membered aryl multi-cyclic ring system, an 8- to 1 1 - membered aryl fused ring system, a 5- or 6- membered heteroaryl ring, an 8- to 1 1 - membered heteroaryl multi-cyclic ring system or an 8- to 1 1 - membered heteroaryl fused ring system, each ring member of the heteroaryl ring or the ring system is selected from C, N, O and S, and each ring or ring system is optionally substituted with R14 on carbon atoms and R15 on hetero atoms; or
Q is independently a 3- to 7- membered nonaromatic carbocyclic ring, a 5-, 6- or 7- membered nonaromatic heterocyclic ring, an 8- to 15- membered nonaromatic multi-cyclic ring system or an 8- to 15- membered nonaromatic fused ring system, each ring member of the nonaromatic ring or the ring system is selected from C, N, O, S(0)a, C(=0), C(=S), S(=NR2) and S(=0)=NR2 & SiRl6R17, and each ring or ring system is optionally substituted with R14 on carbon atoms and R15 on hetero atoms;
R16 and R17 are independently selected from C,-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3- C6 cycloalkyl, C3-C6 halocycloalkyl, C -C6 cycloalkyl C rC6 alkyl, C rC6 alkyl C3-C6 cycloalkyl, C |-C6 haloalkyl C3-C6 cycloalkyl, CrC6 haloalkyl, CrC6 alkoxy and C rC6 haloalkoxy;
R1, R2, R6, R7, R8, R9, R10, R14, R15, R18, R19, R20, R21, R24 and R27 are independently selected from hydrogen, halogen, hydroxy, cyano, nitro, CrC6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CrC6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C ,-C6 alkyl C3-C8 cycloalkyl, C3-C8 cycloalkyl C ,-C6 alkyl, C3-C8 cycloalkyl C3-C8 cycloalkyl, C3-C8 halocycloalkyl C C6 alkyl, C rC6 alkoxy CrC6 alkyl, C3-C8 cycloalkoxy C rC6 alkyl, C |-C6 alkylthio C rC6 alkyl, C C6 alkylsulfinyl CrC6 alkyl, C rC6 alkylsulfonyl C C6 alkyl, C |-C6 alkylamino, CrC6 dialkylamino, CrC6 alkylamino C C6 alkyl, C rC6 dialkylamino C C6 alkyl, C |-C6 haloalkylamino C]-C6 alkyl, C3-C8 cycloalky!amino, C3-C8 cycloalkylamino C C6 alkyl, C Cb alkylcarbonyl, C rC6 haloalkylcarbonyl, C3-C8 cycloalkylcarbonyl, C rCb alkoxycarbonyi, C3- C8 cycloalkoxycarbonyl, C |-C6 al kylaminocarbonyl, C | -C5 dialkylaminocarbonyl, C3-C8 cycloalkylaminocarbonyl, C rC6 haloalkoxy C C6 alkyl, C rC6 hydroxyalkyl, Ci-Cf) hydroxyalkenyl, CrC6 hydroxyalkynyl, C rC6 alkoxy, C rC6 haloalkoxy, C rC6 cycloalkoxy, C3- C8 halocycloalkoxy, C3-C8 cycloalkyl CrC6 alkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2- C6 alkynyloxy, C2-C6 haloalkynyloxy, C C6 alkoxy C rC() alkoxy, C rC6 alkylcarbonyloxy, C,-C6 haloalkylcarbonyloxy, C3-C6 cycloalkylcarbonyloxy, C rC6 alkylcarbonyl C rC(, alkoxy, C rC6 alkylthio, CrC6 haloalkylthio, C3-C8 cycloalkylthio, C C6 alkylsulfinyl, C rC6 haloalkylsulfinyl, C ,-C6 alkylsulfonyl, C C6 haloalkylsulfonyl, C3-C8 cycloalkylsulfonyl, C3-C8 cycloalkylsulfinyl, CrC6 trialkylsilyl, CrC6 alkylsulfonylamino, C,-C6 haloalkylsulfonylamino, CrC6 alkylcarbonylthio, C C6 alkylsulfonyloxy, C ,-C6 alkylsulfinyloxy, arylsulfonyloxy, arylsulfinyloxy, arylsulfonyl, arylsulfinyl, C C6 cyanoalkyl, C2-C6 alkenylcarbonyloxy, CpC6 alkoxy CrC6 alkylthio, Cj-C6 alkylthio C rC6 alkoxy, C2-C6 haloalkenylcarbonyloxy, C C alkoxy C2-C6 alkynyl, C2-C6 alkynylthio, C3-Cg halocycloalkylcarbonyloxy, C2-C6 alkenylamino, C2-C6 alkynylamino, C C6 haloalkylamino, C3-C8 cycloalkyl CrC6 alkylamino, CrC6 alkoxyamino, Cr C6 haloalkoxyamino, C C6 alkylcarbonylamino, C ,-C6 haloalkylcarbonylamino, C,-C6 alkoxycarbonylamino, C2-C6 alkenylthio, C i-C6 haloalkoxycarbonyl, C C6 alkoxy C,-C6 alkylcarbonyl, C,-C6 haloalkoxycarbonylamino, C i-Cf, alkoxy C,-C6 alkylaminocarbonyl, C C6 alkylthiocarbonyl, C3-C8 cycloalkenyloxy C C6 alkyl, C rC6 alkoxy C C6 alkoxycarbonyi, C C6 haloalkoxy CrC6 haloalkoxy, C|-C6 alkoxy C C6 haloalkoxy, C3-C8 halocycloalkoxy CrCc alkyl, C,-C6 dialkylaminocarbonylamino, C ,-C6 alkoxy C2-C6 alkenyl, CrC6 alkylthiocarbonyloxy, C C6 haloalkoxy C rC6 alkoxy, C ]-C6 haloalkylsulfonyloxy, C rC6 alkoxy C C6 haloalkyl, CrC6 dihaloalkylamino, CrC6 dialkoxy CrCf, alkyl, C C6 alkylaminocarbonylamino, C C6 haloalkoxy C]-C6 haloalkyl, CrC6 alkylaminocarbonyl C C6 alkylamino, C rC6 trialkylsilyl C2-C6 alkynyloxy, CrC6 trialkylsilyloxy, C C6 trialkylsilyl C2-C6 alkynyl, CrC6 cyanoalkoxy CrC6 alkyl, CrC6 dialkylthio CrC6 alkyl, C ,-C6 alkoxysulfonyl, C3-C8 halocycloa!koxycarbonyl, CrC6 alkylcy C3-C8 cloalkylcarbonyl, C3-C8 halocyclo C C6 alkylcarbonyl, C2-C6.alkenyloxycarbonyI, C2-C6 alkynyloxycarbonyl, C rC6 cyanoalkoxycarbonyi, C rC6 alkylthio C rC6 alkoxycarbonyi, C2-C6 alkynylcarbonyloxy, C2-C6 haloalkynylcarbonyloxy, cyanocarbonyloxy, C,-C6 cyanoalkylcarbonyloxy, C3-C8 cycloalkylsulphonyloxy, C3-C8 cycloalkyl C]-C6 alkylsulphonyloxy, C3-C8 halocycloalkylsulphonyloxy, C2-C6 alkenylsulphonyloxy, C2-C6 alkynylsulphonyloxy, C rC6 cyanoalkylsulphonyloxy, C2-C6 haloalkenylsulphonyloxy, C2-C6 haloalkynylsulphonyloxy, C2-Cb alkynylcycloalkyloxy, C2-Q, cyanoalkenyloxy, C2-C6 cyanoalkynyloxy, C | -C6 alkoxycarbonyloxy, C2-C6 alkenyloxycarbonyloxy, C2-C6 alkynyloxycarbonyloxy, C rC6 alkoxyalkylcarbonyloxy, sulfilimines, sulfoximines, SF5 or L8Q;
L8 is independently selected from a direct bond, O, S(=0)a, C(=0), C(=S), C(R22)2, C(R2 )2-C(R 2)2, or R23;
5 R4, R 12, and R22 are independently selected from hydrogen, halogen, cyano, hydroxy, aldehyde, C rC6 alky], C2-C6 alkenyl, C2-C6 alkynyl, C C6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C ,-C6 alkoxy CrC6 alkyl, CrC6 alkylthio C,-C6 alkyl, Cr C6 alkylsulfinyl CrC6 alkyl, CrC4 alkylsulfonyl CrC6 alkyl, CrC6 alkylcarbonyl, C r C6 haloalkylcarbonyl, CrC6 alkoxycarbonyl, CpQ, alkoxycarbonyl CrC<, alkyl, C,-C60 alkylaminocarbonyl, C C6 dialkylaminocarbonyl, C ,-C6 alkoxy, CrC6 haloalkoxy, C r
C6 alkylthio, CrC6 haloalkylthio, C C6 alkylsulfinyl, C rC6 haloalkylsulfinyl, CrC6 alkylsulfonyl and C C6 haloalkylsulfonyl;
R3, R13, and R23 are independently selected from hydrogen, C C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, d -Q, haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C C6 alkoxy C r5 C6 alkyl, C C4 alkylthio C,-C6 alkyl, C,-C6 alkylsulfinyl CrC6 alkyl, C,-C6 alkylsulfonyl
C rC6 alkyl, C C6 alkylcarbonyl, C C6 haloalkylcarbonyl, CrC6 alkoxycarbonyl, C r C6 alkoxycarbonyl CrC6 alkyl, CrCf) alkylaminocarbonyl, CrC6 dialkylaminocarbonyl, C |-C6 alkylsulfonyl and C rC6 haloalkylsulfonyl; and salts, metal complexes, N-oxides, isomers, and polymorphs of the compounds of Formula I.
2. The compound as claimed in claim 1 , wherein
T1 is independently selected from 5- or 6- membered heteroaryl ring or 5- or 6- or 7- membered saturated or partial ly saturated heterocyclic ring, wherein each ring member of heteroaryl ring is selected from C, N, O and S, and wherein each ring member of heterocyclic ring is selected from C, N,5 O, S(0)a, C(=0), and C(=S); and T1 is optionally substituted by one or more R1 on C atoms and one or more R2 on hetero atoms;
T2 , T3 and T4 C ,-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CrC6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, CrC6 alkyl C3-C6 cycloalkyl, C3-C6 cycloalkyl C C6 alkyl, C3-C6 cycloalkyl C3-C5 cycloalkyl, C -C6 halocycloalkyl C rC6 alkyl, C3-C6 cycloalkenyl, C3-C60 halocycloalkenyl, C C6 alkoxy C C6 alkyl, C -C6 cycloalkoxy C rC6 alkyl, C rC6 alkylthio C rC6 alkyl, CrC6 alkylsulfinyl CrC6 alkyl, CrC6 alkylsulfonyl CrC6 alkyl, CrC6 alkylamino CrC6 alkyl, C,-C6 dialkylamino CrC6 alkyl, Ci-C6 haioalkylamino C C6 alkyl, C3-C6 cycloalkyiamino CrC6 alkyl, CrC6 alkylcarbonyl, CrC6 haloalkylcarbonyl, C3-C6 cycloalkylcarbonyl, CrC6 alkoxycarbonyl, C3-C6 cycloalkoxycarbonyl, C C6 alkylaminocarbonyl, CrC6 dialkylaminocarbonyl, C3-C6 5 cycloalkylaminocarbonyl, CrC6 haloalkoxy C C6 alkyl, CrC6 hydroxyalkyl, CrC6 alkoxy, CrC6 haloalkoxy, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C3-C6 cycloalkyl CrC6 alkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6haloalkynyloxy, CrC6 alkoxy CrC6 alkoxy, C C6 alkylcarbonyloxy, CrC6 haloalkylcarbonyloxy, C3-C6 cycloalkylcarbonyloxy, CrC6 alkylcarbonyl CrC6 alkoxy, CrC6 alkylthio, CrC6 haloalkylthio, C3-C6 cycloalkylthio, C]-C6 10 alkylsulfinyl, C]-C6 haloalkylsulfinyl, C,-C6 alkylsulfonyl, CrC6 haloalkylsulfonyl, C3-C6 cycloalkylsulfonyl, C|-C6trialkylsilyl, CrC6alkylsulfonylamino, and CrC6 haloalkylsulfonylamino;
L1 is a direct bond or O; and L2 L3 L4, and L5 are independently a direct bond, O, S(=0)a, C(=0), C(=S), C(R22)2;
A is C(R4)2; 5 WisO;
Z is C; the presentation " " in ring D is a single bond;
"n" is an integer ranging from 0 to 9;
G is an optionally substituted 5- or 6- membered heteroaryl ring; 0 L6 and L7 are independently a direct bond, O, C(=0), C(=S), C(R12) and NRl C(=0); and
Q is 5- or 6- membered aryl ring or 5- or 6- membered heteroaryl ring.
3. The compound as claimed m claim 1, wherein
E is E-l; 5 Τ' is selected from Tl to Tl 67; G is selected from Gl to G63; Q is selected from Ql to Q99. The compound as claimed in claim 1, wherein
T1 is selected from Tl and T51 ;
G isGl,G45 andG61;
Q is Q45, Q32, Q33 and Q34.
The compound as claimed in claim 1, comprising
N-((3-biOmophenyi)(methyl)(oxo)- <,-sulfaneyiidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((3-bromophenyl)(methyl)(oxo)- 6-sulfanylidene)thiazole-
4- carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((2,6- dimethylphenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; N-((2,6- dimethylphenyl)(methyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-dimethyl-lH-pyrazol-l- yl)acetyl)piperidin-4-yl)-N-((2,6-dimethylphenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole-4- carboxamide; 2-(l-(2-(3-bromo-2-oxo-5-(trifluoromethyl)pyridin-l(2H)-yl)acetyl)piperidin-4-yl)- N-((2,6-dimethylphenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; 2-(l-(2-(3- chloro-2-oxo-5-(trifluoromethyl)pyridin-l(2H)-yl)acetyl)piperidin-4-yl)-N-((2,6- dil·nethylphenyl)(methyl)(oxo)-λ6-sulfaneylidene)thiazole-4-carbo amide; N-((2,6- dimethylphenyl)(methyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(3-
(trifluoromethyl)phenyl)acetyI)piperidin-4-yl)thiazole-4-carboxamide; N-((2,6- dimethylphenyl)(ethyl)(oxo)- 6-sulfanylidene)-2-(l-^^
l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-
1- yl)acetyl)piperidin-4-yl)-N-((2,6-dimethylphenyl)(ethyl)(oxo)- 6-sulfaneylidene)thiazole-4- carboxamide; 2-(l-(2-(3,5-dimethyl-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((2,6- dimethylphenyl)(ethyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; 2-(l-(2-(3-chloro-2-oxo-
5- (triiluoromethyl)pyridin-l(2H)-yl)acety])piperidin-4-yl)-N-((2,6-dimethylphenyl)(eth
-sulfaneylidene)thiazole-4-carboxamide; N-((2,6-dimethylphenyl)(ethyl)(oxo)- 6- sulfaneylidene)-2-(l-(2-(3-(trifluoromethyl)phenyl)acetyl)piperidin-4-yl)thiazole-4-carboxamide;
2- (l-(2-(3-bromo-2-oxo-5-(trifluoromethyl)pyridin-l(2H)-yl)acetyl)piperidin-4-yl)-N-((2,6- dimethylphenyl)(ethyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; N-((2,6- difluorophenyl)(methyl)(oxo)^-sulfanylidene)-2-(l-(2-(5-methyl-3-(trifluoi methyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((2,6-difluorophenyl)(methyl)(oxo)- 6- sulfaneylidene)thiazole-4-carboxamide; N-((3-bromophenyl)(methyl)(oxo)- 6-sulfaneylidene)-2- (l-(2-(3,5-dimethyl-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3- bromo-2-oxo-5-(trifluoromethyl)pyridin-l(2H)-yl)acetyl)piperidin-4-yl)-N-((3- biOmophenyl)(isopropyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; N-((3- bromophenyl)(methyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(3-chloro-2-oxo-5- (trifluoromethyl)pyridin-l(2H)-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3- bromo-2-oxo-5-(trifluoromethyl)pyridin-l(2H)-yl)acetyl)piperidin-4-yl)-N-((3- bromophenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; N-((2,6- dichlorophenyl)sulfonyl)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperi 4-yl)thiazole-4-carboxamide; N-((3-bromophenyI)(methyl)(oxo)^6-sulfaneylidene)-2-(l-(2-((3- (trifluoromethyl)pyridin-2-yl)oxy)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5- bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((4-brornophenyl)(methyl)(oxo)- 6- sulfaneylidene)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l- yl)acetyl)piperidin-4-yl)-N-((3-chlorophenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole-4- carboxamide; N-((3-chlorophenyl)(methyI)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3- (trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; N-((4- bromophenyl)(methyl)(oxo)^6-sulfaneylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((2-bromophenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole- 4-carboxamide; N-((2-biOmophenyl)(methyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3- (trifluoromethyl)-lH-pyrazol-l-yi)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5- bis(difIuoromethyl)-lH-pyrazol-l-yl)acetyl)pipendin-4-yl)-N-((3-methoxyphenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; N-((4-chlorophenyl)(methyl)(oxo)- 6-sulfaneylidene)- 2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4- carboxamide; (S)-N-((3-bromophenyl)(methyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3- (trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(]-(2-(3,5- bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-(methyl(oxo)(phenyl)- 6- sulfaneylidene)thiazole-4-carboxamide; (S)-2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l- yl)acetyl)piperidin-4-yl)-N-((3-bromopheny])(methyl)(oxo)- 6-sulfaneylidene)thiazole-4- carboxamide; (S)-2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N- (methyl(oxo)(phenyl)^6-sulfaneylidene)thiazo]e-4-carboxamide; (R)-2-(l-(2-(3,5- bis(difluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4-yl)-N-(methyl(oxo)(phenyl)- 6- sulfaneylidene)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-l H-pyrazol-1 - yl)acetyl)piperidin-4-yl)-N-((2,6-dichlorophenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole-4- carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4-yl)-N-((3- bi mophenyl)(isopi pyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; (R)-2-(l-(2-(3,5- bis(difluorometbyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4-yl)-N-((3-bromophenyl)(methyl)(oxo)- 6- sulfaneylidene)thiazole-4-carboxamide; N-((2,6-dichlorophenyl)(methyl)(oxo)- 6- sulfaneylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4- yl)thiazole-4-carboxamide; N-((3-methoxyphenyl)(methyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5- methyl-3-(trifluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l- (2-(3,5-bis(difluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4-yl)-N-((3,4- dichloiOphenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; N-((3- bromophenyl)(isopi pyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3-(tril1uoi methyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((3-bromophenyl)(ethyl)(oxo)- 6-sulfaneylidene)thiazole-4- carboxamide; N-((3-blΌmophenyl)(ethyl)(oxo)-λ6-sulfaneylidene)-2-(l-(2-(5-lTlethyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5- bis(difluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4-yl)-N-(methyl(oxo)(o-tolyl)- 6- sulfaneylidene)thiazole-4-carboxamide; N-methyl(oxo)(0-tolyl)- 6-sulfanylidene)-2-(l-(2-(5- methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxaiTiide; 2-(l- (2-(3,5-bis(difluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4-yl)-N-((3- fluorophenyl)(methyl)(oxo)^6-sulfaneylidene)thiazole-4-carboxamide; N-((3- fluorophenyl)(methyl)(oxo)^6-sulfaneylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; N-(methyl(oxo)(pyridin-2-yl)^6- sulfaneylidene)-2-(]-(2-(5-methyl-3-(trifluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4- yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4- yI)-N-(methyl(oxo)(pyridin-2-yl)^6-sulfaneylidene)thiazole-4-carboxamide; 2-(l-(2-(3,5- bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((2-methoxyphenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; N-((2-methoxyphenyl)(methyl)(oxo)- 6- sulfaneylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4- yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4- yl)-N-((2,4-difluoiOphenyl)(methyl)(oxo)- <,-sulfaneylidene)thiazole-4-carboxamide; N-((2,4- difluoiOphenyl)(methyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3-(triiluoiOmethyl)-lH- pyrazol-1 -yl)acetyI)piperidin-4-yl)thiazole-4-carboxamide; N-(methyl(oxo)(3- (trifluoromethoxy)phenyl)- 6-sulfaneylidene)-2-(l-(2-(5-iTiethyl-3-(triflLioromethyl)-l H-pyrazol- 1 -yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-( 1 -(2-(3,5-bis(difluoromethyl)-l H-pyrazol- l-yl)acetyl)piperidin-4-yl)-N-(methyl(oxo)(3-(trifluoromethoxy)phenyl)- 6- sulfaneylidene)thiazole-4-carboxamide; N-((3,5-dichlorophenyl)(rnethyl)(oxo)^6- sulfaneylidene)-2-(l-(2-(5-methy]-3-(trifluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4- yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4- yl)-N-((3,5-dichlorophenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; N-((3- bromophenyl)(methyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(3-cyano-2-oxo-5-
(trifluorornethyl)pyridin-l(2H)-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; N- (methyl(oxo)(3-(trifluoromethyl)benzyl)^6-sulfaneylidene)-2-(l-(2-(5-rnethyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; N- (methyl(oxo)(p-tolyl)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-l H-pyrazol-1 - yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-l H-pyrazol-1 - yl)acetyl)piperidin-4-yl)-N-(methyl(oxo)(p-tolyl)- 6-sulfaneylidene)thiazole-4-carboxarnide; 2- (l-(2-(3,5-bis(difluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4-yl)-N-((3- cblorophenyl)(ethyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; N-((3- chlorophenyl)(ethyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-iTiethyl-3-(trifluoiOmethyl)-lH-pyrazol- l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol- l-yl)acetyl)piperidin-4-yl)-N-((3-chlorophenyl)(isopropyl)(oxo)- 6-sulfaneylidene)thiazole-4- carboxamide; N-((3-chlorophenyl)(isopi pyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3- (trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5- bis(difluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4-yl)-N-(methyl(oxo)(3- (trifluoromethyl)benzyl)- 6-sulfaneylidene)thiazole-4-carboxamide; N-((4- methoxyphenyl)(methyl)(oxo)-λ6-SLllfaneyΠdene)-2-(l-(2-(5-lTlethyl-3-(trifluorornethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((4-methoxyphenyi)(methyl)(oxo)- 6- sulfaneylidene)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-l H-pyrazol-1 - yl)acetyl)piperidin-4-yl)-N-((4-bromophenyl)(ethyl)(oxo)- 6-sulfaneylidene)thiazole-4- carboxamide; N-((4-bromophenyl)(ethyl)(oxo)^6-sulfaneylidene)-2-(l-(2-(5-methyl-3- (trifluorornethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxarnide; 2-(l-(2-(3,5- bis(difluoromethyl)-] H-pyrazol-1 -yl)acetyl)piperidin-4-yl)-N-((4-bromophenyl)(isopropyl)(oxo)- λ6-sulfaneylidene)thiazole-4-carboxamide; N-((4-bromophenyl)(isopi pyl)(oxo)- 6- sulfaneylidene)-2-(l -(2-(5-methyl-3-(trifluoromethyl)-l H-pyrazol-1 -yl)acetyl)piperidin-4- yl)thiazole-4-carboxamide; (4-bromophenyl)(methyl)(((2-(l -(2-(5-methyl-3-(trifluoromethyl)- lH-pyrazol-l-yl)acetyl)pipendin-4-yl)thiazol-4-yl)methyl)imino)^6-sulfanone; (((2-(l-(2-(3,5- bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-y!)thiazol-4-yl)methyl)imino)(4- bromophenyl)(methyl)- 6-sulfanone; (((2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l- yl)acetyl)piperidin-4-yl)thiazol-4-yl)methyl)imin^ (3- bromophenyl)(methyl)(((2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin- 4-yl)thiazol-4-yl)methyl)imino)- 6-sulfanone; N-((2-bromophenyl)(isopiOpyl)(oxo)- i>- sulfaneylidene)-2-(l-(2-(5-methyI-3-(tnfluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4- yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4- yl)-N-((2-bromophenyl)(isopropyl)(oxo)^6-sulfaneylidene)thiazole-4-carboxamide; N-((3,4- difluorophenyl)(methyl)(oxo)- 6-su]faneylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((3,4-difluoi phenyl)(methyl)(oxo)- 6- sulfanylidene)thiazole-4-carboxamide; N-((2,6-difluorophenyl)(isopropyl)(oxo)- 6- sulfanylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH^yrazol-l-yl)acetyl)piperidin-4- yl)thiazole-4-carboxamide; 3-(N-(2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l- y])acetyl)piperidin-4-yl)thiazole-4-carbonyl)propan-2-ylsulfonimidoyl)phenyl methanesulfonate; 3-(N-(2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4 carbony!)propan-2-ylsulfonimidoyl)phenyl methanesulfonate; 2-(l-(2-(3,5-bis(difluoromethyl)- lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((2-bromophenyl)(ethyl)(oxo)- 6- sulfaneylidene)thiazole-4-carboxamide; 3-(N-(2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazoI-l- yl)acetyl)piperidin-4-yl)thiazo]e-4-carbonyl)ethylsulfonimidoyl)phenyl methanesulfonate; 3-(N- (2-(l-(2-(5-methyl-3-(trifluoi methyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4- carbonyl)ethylsulfonimidoyl)phenyl methanesulfonate; N-((2,6-difluorophenyI)(ethyl)(oxo)- 6- sulfanylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4- yl)thiazole-4-carboxamide; N-((2-bromophenyl)(ethyl)(oxo)^c-sulfaneylidene)-2-(l-(2-(5- methyl-3-(tritluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; N- (methyl(oxo)(m-tolyl)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3-(trifluoiOmethyl)-lH-pyrazol-l- yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l- yl)acetyl)piperidin-4-yl)-N-(methyl(oxo)(m-tolyl)^6-sulfaneylidene)thiazole-4-carboxamide; 2- (l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((3- bromophenyl)(oxo)(trifluoromethyl)^6-sulfaneylidene)thiazole-4-carboxamide; 2-(l-(2-(3,5- bis(difluoromethyl)-l H-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-(ethyl(3-fiuoi phenyl)(oxo)- 6- sulfaneylidene)thiazole-4-carboxamide; N-(ethyl(3-fluorophenyl)(oxo)- 6-sulfaneylidene)-2-( 1 - (2-(5-methyl-3-(trifluoromethyl)-lH^yrazo
N-((3,5-difluorophenyl)(methyl)(oxo)- -sulfaney]idene)-2-(l-(2-(5H^ethy]-3-(trifluoromethyl)- lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; N-((3,4- dichlorophenyl)(methyl)(oxo)- 6-suIfaneyIidene)-2-(l-(2-(5-methy]-3-(tritluoiOiTiethyl)-lH- pyrazol-l-y])acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-]H- pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((2,6-difluorophenyl)(ethyl)(oxo)- <'- sulfanylidene)thiazole-4-carboxamide; N-((3,5-dimethylphenyl)(methyl)(oxo)- 6-sulfaneylidene)- 2-(l-(2-(5-methyl-3-(trifluoroiTiethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4- carboxamide; N-((3-bromophenyl)(cyclopropylmethyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5- methyl-3-(trifluoromethyl)-lH-pyrazol-]-yl)acetyI)piperidin-4-y])thiazole-4-carboxamide; N-((4- i]uoropheny])(methyl)(oxo)- 6-su]faneylidene)-2-(]-(2-(5-methyl-3-(trifluoiOmethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-( l-(2-(3,5-bis(difluoromethyl)-lH- pyrazoi-l-yl)acetyl)piperidin-4-yl)-N-((3,5-dimethylphenyl)(methyl)(oxo)^6- sulfaneylidene)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l- yl)acetyl)piperidin-4-yl)-N-((4-fluol phenyl)(methy])(oxo)-λ6-sulfaneyIidene)thiazole-4- carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l-yl)acetyI)piperidin-4-yl)-N-((3- hydroxyphenyl)(isopropyl)(oxo)^6-sulfany]idene)thiazoIe-4-carboxamide; 2-(l-(2-(3,5- bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((3,5- difluorophenyl)(methyl)(oxo)-λ6-sulfaneylidene)thiazole-4-carbo amide; 2-(l-(2-(3,5- bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((3- bromophenyl)(cyclopropyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; N-((3- bromophenyl)(cyc]opropyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH- pyrazol-l-yl)acety])piperidin-4-yl)tbiazole-4-carboxamide; N-((3- hydroxyphenyl)(isopropyl)(oxo)- 6-suifanylidene)-2-(l-(2-(5-methyI-3-(tri luoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((2,6-dichlorophenyl)(isopropyl)(oxo)^6- sulfanylidene)thiazole-4-carboxamide; N-((2,6-dichlorophenyl)(ethyi)(oxo)- 6-sulfanylidene)-2- (l-(2-(5-methyl-3-(tnfluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4- carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((2,6- dichIorophenyI)(ethyI)(oxo)- 6-suIfanylidene)thiazoIe-4-carboxamide; N-((2,6- dichlorophenyl)(isopi pyl)(oxo)- 6-sulfanylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH- pyrazol-l-yl)acetyl)piperidin-4-yI)thiazole-4-carboxamide; 2-(l-(2-(3,54jis(difluoromethy!)-lH- pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((2-chlorophenyl)(methyl)(oxo)- 6-sulfanylidene)thiazole- 4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-l H-pyrazoI-1 -yl)acetyl)piperidin-4-yl)-N- (methyl(4-nitrophenyl)(oxo)- 6-sulfanylidene)thiazole-4-carboxamide; N-((4- bromophenyl)(methyl)(oxo)^6-sulfaneylidene)-2-(l-(2-(5-(difluoiOmethyl)-lH-pyrazol-l- yl)acetyl)piperidin-4-yI)thiazole-4-carboxamide; N-((4-bromophenyl)(methyl)(oxo)- 6- sulfaneylidene)-2-(l-(2-(5-(trifluoromethyl)-2H etrazol-2-yl)acetyl)pipendin-4-yl)thiazole-4- carboxamide; N-((3-bromophenyl)(methyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-(difluoromethyl)- lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; N-((3- bromophenyl)(methyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-(trifluoromethyl)-2H-tetrazol-2- yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; N-(2-(l-(2-(3,5-bis(di luoromethyl)-lH-pyrazol-
1- yl)acetyl)piperidin-4-yl)thiazol-4-yl)-2,
6-dichlorobenzenesulfonamide; 2-(l-(2-(3,5- bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((3,5- bis(tnfluoromethyl)phenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; N- (rnethyl(oxo)(3-(trifluoromethyl)phenyl)^6-sulfaneylidene)-2-(l-(2-(5-methyl-3- (trifluoromethyl)-lH-pyrazol-l-y!)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5- bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((4-chlorophenyl)(methyl)(oxo)- 6- sulfaneylidene)thiazole-4-carboxamide; N-(methyl(4-nitrophenyl)(oxo)- 6-sulfanylidene)-2-(l- (2-(5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxa
2- (l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((4- bromophenyl)(isopentyl)(oxo)- 6-sulfanylidene)thiazole-4-carboxamide; N-((4- bromophenyl)(isopentyl)(oxo)- 6-sulfanylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH- pyrazol- 1 -yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-( 1 -(2-(3,5-bis(difluoromethyl)-l H- pyrazol-l-yl)acetyl)piperidin-4-yl)-N-((2-chloro-6-methylphenyl)(methyl)(oxo)- 6- sulfanylidene)thiazole-4-carboxamide; l-(2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-l- yl)acetyl)piperidin-4-yl)thiazol-4-yl)-3-((3-bromophenyl)(methyl)(oxo)- 6-sulfaneylidene)urea; l-((3-bromophenyl)(methyl)(oxo)- 6-sulfaneylidene)-3-(2-(l-(2-(5-methyl-3-(trifluoromethyl)- lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazol-4-yl)urea; N-((2-chloro-6- methylphenyl)(methyl)(oxo)^6-sulfanylidene)-2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH-pyrazol- l-y])acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5-bis(difluoromethyl)-lH-pyrazol-
1- yl)acetyl)piperidin-4-yl)-N-((3-bromophenyl)(methyl)(oxo)- 6-sulfaneyIidene)thiazole-4- carboxamide; N-((3-bromophenyl)(methyl)(oxo)- 6-sulfaneylidene)-2-(4-(2-(5-methyl-3- (trifluoromethyl)-] H-pyrazol-l-yl)acetyl)piperazin-l-yl)thiazole-4-carboxamide; 2-(4-(2-(3,5- bis(difluoromethyI)-lH-pyrazol-l-yl)acetyl)piperazin-l-yl)-N-((4-bromophenyl)(methyl)(oxo)- 6-sulfaneylidene)thiazole-4-carboxamide; N-((4-bromophenyl)(methyl)(oxo)- 6-sulfaneyIidene)-
2- (4-(2-(3-(difluoromethyl)-l H-pyrazol-]-y])acetyl)piperazin-l-yl)thiazole-4-carboxamide; N- ((4-bromophenyl)(methyl)(oxo)- 6-sulfaney!idene)-2-(4-(2-(5-methyl-3-(trifluoromethyl)-lH- pyrazol-1 -yl)acetyl)piperazin-l-yl)thiazole-4-carboxamide; N-(methyl(oxo)(pyridin-2-yl)- 6- sulfaneylidene)-2-(l-(2-(5-methyl-3-(tniluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4- yl)thiazole-4-carboxamide; 3-(S-methyl-N-(2-(l-(2-(5-methyl-3-(trifluoi methyl)-lH-pyrazol-l- yl)acetyl)piperidin-4-yl)thiazole-4-carbonyl)sulfonimidoyl)phenyl methanesulfonate; 2-(l-(2- (3,5-bis(difluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)-N-(methyl(oxo)(3- (trifluoromethyl)phenyl)- 6-su]faneylidene)thiazole-4-carboxamide; N-((4- chlorophenyl)(isopropyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3-(tnfluoromethy!)-lH- pyrazol-1 -yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; l-((4-bromophenyl)(methyl)(oxo)- 6- sulfaneylidene)-3-(2-(l-(2-(5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl)acety!)piperidin-4- yl)thiazol-4-yl)urea; 1 -(2-( 1 -(2-(3,5-bis(difluoromethyl)-l H-pyrazol- 1 -yl)acetyl)piperidin-4- yl)thiazol-4-yI)-3-((4-bromophenyl)(methyl)(oxo)^6-sulfaneylidene)urea; l-((3- bromophenyl)(chloromethyl)(oxo)^6-sulfaneylidene)-3-(2-(l-(2-(5-methyl-3-(trifluoiOmethyl)- 1 H-pyrazol- l-yl)acetyl)piperidin-4-yl)thiazol-4-yl)urea; l-(2-(l-(2-(3,5-bis(difluoromethyl)-l H- pyrazol-l-yl)acetyl)piperidin-4-yl)thiazol-4-yl)-3-((3-bromophenyl)(chloromethyl)(oxo)^6- sulfaneylidene)urea; N-((3-bi mophenyl)(cyclohexyl)(oxo)^6-sulfaneylidene)-2-(l-(2-(5-methyl- 3-(trifluoromethyl)-lH-pyrazol-l -yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; N-((3- bromophenyl)(isopentyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3-(trifluoiOmethyl)-lH- pyrazol-l-yl)acetyI)piperidin-4-yl)thiazole-4-carboxamide; N-((3,5- bis(trifluot methyl)phenyl)(methyl)(oxo)- 6-sulfaneylidene)-2-(l-(2-(5-methyl-3- (trifluoromethyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 3-(N-(2-(l-(2- (3,5-bis(difluoromethyl)-l H-pyrazol- l-yl)acetyl)piperidin-4-yl)thiazole-4-carbonyl)-S- methylsulfonimidoyl)phenyl methanesulfonate; 2-(l -(2-(3,5-bis(difluoromethyl)-l H-pyrazol- 1 - yl)acetyl)piperidin-4-yl)-N-((3-bromophenyl)(isopentyl)(oxo)- 6-sulfaneylidene)thiazole-4- carboxamide; N-(methyl(oxo)(4-(tnfluoromethyl)phenyl)^6-sulfanylidene)-2-(l-(2-(5-methyl-3- (trifluoi methyl)-lH-pyrazol-l-yl)acetyl)piperidin-4-yl)thiazole-4-carboxamide; 2-(l-(2-(3,5- bis(difluoromethyl)-l H-pyrazol- l-yl)acetyl)piperidin-4-yl)-N-(methyl(oxo)(4- (trifluoromethyl)phenyl)- 6-sulfanylidene)thiazole-4-carboxamide; 2-(l-(2-(3,5- bis(difluoromethyl)-l H-pyrazol- l-yl)acetyl)piperidin-4-yl)-N-(oxodiphenyl- 6- sulfanylidene)thiazole-4-carboxamide; and 2-(l-(2-(5-methyl-3-(trifluoromethyl)-l H-pyrazol- 1- yl)acetyl)piperidin-4-yl)-N-(oxodiphenyl- 6-sulfanylidene)thiazole-4-carboxamide. position for controlling or preventing phytopathogenic micro-organisms comprising;
the compound of Formula I as claimed in claim 1, and
one or more inert carriers.
7. The composition as claimed in claim 6, further comprises one or more active compatible compounds selected from fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilizers and nutrients.
8. The composition as claimed in claim 6, wherein the concentration of the compound of Formula I ranges 5 from 1 to 90% by weight with respect to the total weight of the composition, preferably from 5 to 50% by weight with respect to the total weight of the composition.
9. A combination comprising;
a. a compound of Formula I; and
b. one or more active compatible compounds selected from fungicides, insecticides, nematicides,0 acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilizers and nutrients.
10. Use of compound of Formula I as claimed claim 1 , for controlling or preventing phytopathogenic fungi, stramenopiles, bacteria, insects, nematodes, trematodes and mites in agricultural crops and or horticultural crops.
1 1 . Use of composition as claimed in claim 6, for controlling or preventing phytopathogenic fungi,5 stramenopiles, bacteria, insects, nematodes, trematodes and mites in agricultural crops and or horticultural crops.
12. Use of combination as claimed in claim 9, for controlling or preventing phytopathogenic fungi, stramenopiles, bacteria, insects, nematodes, trematodes and mites in agricultural crops and or horticultural crops.
. Use of compound as claimed in claim 10, for controlling or preventing phytopathogenic fungi and oomycetes in agricultural crops and or horticultural crops.
14. Use of the compound as claimed in claim 10, wherein the agricultural crops are selected from cereals, corn, rice, soybean and other leguminous plants, fruits and fruit trees, grapes, nuts and nut trees, citrus and citrus trees, any horticultural plants, cucurbitaceae, oleaginous plants, tobacco, coffee, tea, cacao, sugar beet,5 sugar cane, cotton, potato, tomato, onions, peppers and other vegetables, and ornamentals.
1 5. A method of controlling or preventing infestation of useful plants by phytopathogenic micro-organisms in agricultural crops and or horticultural crops wherein the compound of Formula 1 claimed in claim 1 , is applied to the plants, to parts thereof or the loci thereof.
16. A method of controlling or preventing infestation of useful plants by phytopathogenic micro-organisms in 5 agricultural crops and or horticultural crops wherein the compound of Formula I claimed in claim 1 , is applied to seeds.
17. A process for preparing a compound of Formula I, wherein the process comprises steps of
a. reacting JQ-1 with a compound of Formula 5 to obtain a compound of Formula 4:
Figure imgf000111_0001
0 wherein, R28 is -C(=0)OH, -C(=0)C1, -C(=0)N3, -CH2OH or -CH2X; wherein X is CI, Br or I; R1 G, L6 and Q each are as defined in claim 1 ;
b. converting the compound of For a compound of Formula 2 by de-protection reaction:
Figure imgf000111_0002
wherein, R", G, L6 and Q each are as defined in claim 1 ;
the compound of Formula 2 is reacted with a compound of Formula E-I A to obtain the compound of Formula I:
Figure imgf000111_0003
wherein, R", G, L6, Q, W and T 1 each are as defined in claim 1 .
8. Compounds of Formula 4 and 2:
0 4
wherein, R", G, L6, Q and W each are as defined in claim 1 .
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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021094904A2 (en) 2019-11-11 2021-05-20 Pi Industries Ltd. Novel sulfilimines or sulfoximines containing fungicidal heterocyclic compounds
WO2021094905A1 (en) 2019-11-11 2021-05-20 Pi Industries Ltd. 1 -(4-(4-(5-phenyl-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1 -yl)-ethan-1 -one derivatives and related compounds as fungicides for crop protection
WO2021094903A1 (en) 2019-11-11 2021-05-20 Pi Industries Ltd. 1-(4-(4-(5-phenyl-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1-yl)-ethan-1-one derivatives and related compounds as fungicides for crop protection
WO2022130188A1 (en) 2020-12-15 2022-06-23 Pi Industries Ltd. Agrochemical composition comprising piperidine thiazole compounds
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Citations (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004050637A2 (en) 2002-12-03 2004-06-17 Axys Pharmaceuticals, Inc. 2-(2-hydroxybiphenyl-3-yl)-1h-benzoimidazole-5-carboxamidine derivatives as factor viia inhibitors
WO2006071730A1 (en) 2004-12-27 2006-07-06 Astrazeneca Ab Pyrazolone compounds as metabotropic glutamate receptor agonists for the treatment of neurological and psychiatric disorders
WO2006116713A1 (en) 2005-04-27 2006-11-02 Amgen Inc. Substituted amide derivatives as protein kinase inhibitors
US20070049574A1 (en) 2005-08-31 2007-03-01 Kurt Amrein New pyrazolones as 11b-HSD1 inhibitors for diabetes
WO2007039563A1 (en) 2005-09-30 2007-04-12 N.V. Organon 9-azabicyclo [3 . 3 . 1] nonane derivatives as monoamine reuptake inhibitors
WO2008013622A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2009094445A2 (en) 2008-01-25 2009-07-30 E. I. Du Pont De Nemours And Company Fungicidal hetercyclic compounds
WO2009094407A2 (en) 2008-01-25 2009-07-30 E. I. Du Pont De Nemours And Company Fungicidal amides
WO2010065579A2 (en) 2008-12-02 2010-06-10 E. I. Du Pont De Nemours And Company Fungicidal heterocyclic compounds
WO2010123791A1 (en) 2009-04-22 2010-10-28 E. I. Du Pont De Nemours And Company Solid forms of an azocyclic amide
WO2011076699A1 (en) 2009-12-21 2011-06-30 Bayer Cropscience Ag Bis(difluormethyl)pyrazoles used as fungicides
WO2011085170A1 (en) 2010-01-07 2011-07-14 E. I. Du Pont De Nemours And Company Fungicidal heterocyclic compounds
WO2012020060A1 (en) 2010-08-11 2012-02-16 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives as fungicides
WO2012025557A1 (en) 2010-08-25 2012-03-01 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives as fungicides
WO2012055837A1 (en) 2010-10-27 2012-05-03 Bayer Cropscience Ag Heteroaryl piperidine and heteroaryl piperazine derivatives as fungicides
WO2012082580A2 (en) 2010-12-17 2012-06-21 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2012104273A1 (en) 2011-02-01 2012-08-09 Bayer Cropscience Ag Heteroaryl piperidine and heteroaryl piperazine derivatives as fungicides
WO2013037768A1 (en) 2011-09-15 2013-03-21 Bayer Intellectual Property Gmbh Piperidine pyrazoles as fungicides
WO2013098229A2 (en) 2011-12-27 2013-07-04 Bayer Intellectual Property Gmbh Heteroarylpiperidine and piperazine derivatives as fungicides
WO2013127808A1 (en) 2012-03-02 2013-09-06 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2013127784A1 (en) 2012-03-02 2013-09-06 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2014071044A1 (en) 2012-11-01 2014-05-08 Allergan, Inc. Substituted 6,7-dialkoxy-3-isoquinoline derivatives as inhibitors of phosphodiesterase 10 (pde10a)
WO2014075874A1 (en) 2012-11-13 2014-05-22 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2014075873A1 (en) 2012-11-13 2014-05-22 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2014118142A1 (en) 2013-02-01 2014-08-07 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2014118143A1 (en) 2013-02-04 2014-08-07 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2014154530A1 (en) 2013-03-25 2014-10-02 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2014179144A1 (en) 2013-04-29 2014-11-06 E. I. Du Pont De Nemours And Company Fungicidal heterocyclic compounds
WO2014206896A1 (en) 2013-06-24 2014-12-31 Bayer Cropscience Ag Piperidinecarboxylic acid derivatives as fungicides
WO2015028457A1 (en) 2013-08-28 2015-03-05 Bayer Cropscience Ag Malonic ester derivatives of heteroarylpiperidines and -piperazines as fungicides
US20150216168A1 (en) * 2012-09-05 2015-08-06 Bayer Cropscience Ag Use of substituted 2-amidobenzimidazoles, 2-amidobenzoxazoles and 2-amidobenzothiazoles or salts thereof as active substances against abiotic plant stress
WO2015144571A1 (en) 2014-03-24 2015-10-01 Bayer Cropscience Ag Phenylpiperidinecarboxamide derivatives as fungicides
WO2016024350A1 (en) 2014-08-13 2016-02-18 株式会社エス・ディー・エス バイオテック Condensed 11-membered ring compounds and agricultural and horticultural fungicide containing same
WO2017076739A1 (en) 2015-11-03 2017-05-11 Basf Se Use of substituted oxadiazoles for combating phytopathogenic fungi
WO2017109858A1 (en) 2015-12-22 2017-06-29 株式会社エス・ディー・エス バイオテック Condensed 11-membered ring compound, and agricultural and horticultural germicide including same
WO2017109855A1 (en) 2015-12-22 2017-06-29 株式会社エス・ディー・エス バイオテック Thiazole compound, and agricultural and horticultural germicide including same

Patent Citations (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004050637A2 (en) 2002-12-03 2004-06-17 Axys Pharmaceuticals, Inc. 2-(2-hydroxybiphenyl-3-yl)-1h-benzoimidazole-5-carboxamidine derivatives as factor viia inhibitors
WO2006071730A1 (en) 2004-12-27 2006-07-06 Astrazeneca Ab Pyrazolone compounds as metabotropic glutamate receptor agonists for the treatment of neurological and psychiatric disorders
WO2006116713A1 (en) 2005-04-27 2006-11-02 Amgen Inc. Substituted amide derivatives as protein kinase inhibitors
US20070049574A1 (en) 2005-08-31 2007-03-01 Kurt Amrein New pyrazolones as 11b-HSD1 inhibitors for diabetes
WO2007039563A1 (en) 2005-09-30 2007-04-12 N.V. Organon 9-azabicyclo [3 . 3 . 1] nonane derivatives as monoamine reuptake inhibitors
WO2008013622A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2008013925A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
US20100292275A1 (en) * 2008-01-25 2010-11-18 E.I. Du Pont De Nemours And Company Fungicidal heterocyclic compounds
WO2009094445A2 (en) 2008-01-25 2009-07-30 E. I. Du Pont De Nemours And Company Fungicidal hetercyclic compounds
WO2009094407A2 (en) 2008-01-25 2009-07-30 E. I. Du Pont De Nemours And Company Fungicidal amides
WO2010065579A2 (en) 2008-12-02 2010-06-10 E. I. Du Pont De Nemours And Company Fungicidal heterocyclic compounds
WO2010123791A1 (en) 2009-04-22 2010-10-28 E. I. Du Pont De Nemours And Company Solid forms of an azocyclic amide
WO2011076699A1 (en) 2009-12-21 2011-06-30 Bayer Cropscience Ag Bis(difluormethyl)pyrazoles used as fungicides
WO2011085170A1 (en) 2010-01-07 2011-07-14 E. I. Du Pont De Nemours And Company Fungicidal heterocyclic compounds
WO2012020060A1 (en) 2010-08-11 2012-02-16 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives as fungicides
WO2012025557A1 (en) 2010-08-25 2012-03-01 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives as fungicides
WO2012055837A1 (en) 2010-10-27 2012-05-03 Bayer Cropscience Ag Heteroaryl piperidine and heteroaryl piperazine derivatives as fungicides
WO2012082580A2 (en) 2010-12-17 2012-06-21 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
US20130261154A1 (en) * 2010-12-17 2013-10-03 E I Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2012104273A1 (en) 2011-02-01 2012-08-09 Bayer Cropscience Ag Heteroaryl piperidine and heteroaryl piperazine derivatives as fungicides
WO2013037768A1 (en) 2011-09-15 2013-03-21 Bayer Intellectual Property Gmbh Piperidine pyrazoles as fungicides
WO2013098229A2 (en) 2011-12-27 2013-07-04 Bayer Intellectual Property Gmbh Heteroarylpiperidine and piperazine derivatives as fungicides
WO2013127808A1 (en) 2012-03-02 2013-09-06 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2013127784A1 (en) 2012-03-02 2013-09-06 Syngenta Participations Ag Microbiocidal pyrazole derivatives
US20150216168A1 (en) * 2012-09-05 2015-08-06 Bayer Cropscience Ag Use of substituted 2-amidobenzimidazoles, 2-amidobenzoxazoles and 2-amidobenzothiazoles or salts thereof as active substances against abiotic plant stress
WO2014071044A1 (en) 2012-11-01 2014-05-08 Allergan, Inc. Substituted 6,7-dialkoxy-3-isoquinoline derivatives as inhibitors of phosphodiesterase 10 (pde10a)
WO2014075874A1 (en) 2012-11-13 2014-05-22 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2014075873A1 (en) 2012-11-13 2014-05-22 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2014118142A1 (en) 2013-02-01 2014-08-07 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2014118143A1 (en) 2013-02-04 2014-08-07 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2014154530A1 (en) 2013-03-25 2014-10-02 Syngenta Participations Ag Microbiocidal pyrazole derivatives
WO2014179144A1 (en) 2013-04-29 2014-11-06 E. I. Du Pont De Nemours And Company Fungicidal heterocyclic compounds
WO2014206896A1 (en) 2013-06-24 2014-12-31 Bayer Cropscience Ag Piperidinecarboxylic acid derivatives as fungicides
WO2015028457A1 (en) 2013-08-28 2015-03-05 Bayer Cropscience Ag Malonic ester derivatives of heteroarylpiperidines and -piperazines as fungicides
WO2015144571A1 (en) 2014-03-24 2015-10-01 Bayer Cropscience Ag Phenylpiperidinecarboxamide derivatives as fungicides
WO2016024350A1 (en) 2014-08-13 2016-02-18 株式会社エス・ディー・エス バイオテック Condensed 11-membered ring compounds and agricultural and horticultural fungicide containing same
WO2016024434A1 (en) 2014-08-13 2016-02-18 株式会社エス・ディー・エス バイオテック Condensed 11-member ring compound and agriculture and horticultural fungicide comprising same
WO2017076739A1 (en) 2015-11-03 2017-05-11 Basf Se Use of substituted oxadiazoles for combating phytopathogenic fungi
WO2017109858A1 (en) 2015-12-22 2017-06-29 株式会社エス・ディー・エス バイオテック Condensed 11-membered ring compound, and agricultural and horticultural germicide including same
WO2017109855A1 (en) 2015-12-22 2017-06-29 株式会社エス・ディー・エス バイオテック Thiazole compound, and agricultural and horticultural germicide including same

Non-Patent Citations (13)

* Cited by examiner, † Cited by third party
Title
"Palladium in Heterocyclic Chemistry: A Guide for the Synthetic Chemist", 2000, ELSEVIER
ARKIVOC, 2006, pages 128 - 133
C. A. ZIFICSAK; D. J. HLASTA, TETRAHEDRON, vol. 60, 2004, pages 8991 - 9016
CAMPOS ET AL., TETRAHEDRON LETTERS, 1997
CANIBANO; RODRIGUEZ; SANTOS; SANZ-TEJEDOR; CARRENO; GONZALEZ; GARCIA-RUANO, SYNTHESIS, vol. 14, 2001, pages 2175 - 2179
GIBERT ET AL., PHARMACEUTICAL CHEMISTRY JOURNAL, vol. 41, no. 3, 2007, pages 154 - 156
GUILLAUMET, TETRAHEDRON LETTERS, vol. 45, no. 35, 2004, pages 6633 - 6636
JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 30, no. 1, 1993, pages 49 - 54
KATRIZKY ET AL., J. CHEM. SOC. PERKIN TRANS. II, 1987, pages 969 - 975
MULLER, MONA SHEF EFUER CHEMIE, vol. 89, 1958, pages 23 - 35
SULZER-MOSSE ET AL., BIOORGANIC & MEDICINAL CHEMISTRY, vol. 23, 2015, pages 2129 - 2138
THEODORA W. GREENE; PETER G. M. WUTS: "Protective Groups in Organic Synthesis", 1999, WILEY-INTERSCIENCE, pages: 494 - 653
ZHANG, PEI-ZHI ET AL., TETRAHEDRON, vol. 72, no. 23, 2016, pages 3250 - 3255

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021094904A2 (en) 2019-11-11 2021-05-20 Pi Industries Ltd. Novel sulfilimines or sulfoximines containing fungicidal heterocyclic compounds
WO2021094905A1 (en) 2019-11-11 2021-05-20 Pi Industries Ltd. 1 -(4-(4-(5-phenyl-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1 -yl)-ethan-1 -one derivatives and related compounds as fungicides for crop protection
WO2021094903A1 (en) 2019-11-11 2021-05-20 Pi Industries Ltd. 1-(4-(4-(5-phenyl-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1-yl)-ethan-1-one derivatives and related compounds as fungicides for crop protection
WO2021094904A3 (en) * 2019-11-11 2021-06-24 Pi Industries Ltd. 4-(4-(4,5-dihydroisoxazol-3-yl)thiazol-2-yl) piperidine sulfilimine and sulfoximine derivatives and related compounds as fungicides for crop protection
CN114761403A (en) * 2019-11-11 2022-07-15 Pi工业有限公司 1- (4- (4- (5-phenyl-4, 5-dihydroisoxazol-3-yl) thiazol-2-yl) piperidin-1-yl) -ethan-1-one derivatives and related compounds as crop protection fungicides
CN115052875A (en) * 2019-11-11 2022-09-13 Pi工业有限公司 4- (4- (4, 5-dihydroisoxazol-3-yl) thiazol-2-yl) piperidinethimine or sulfoximine derivatives as fungicides for crop protection and related compounds
CN115052875B (en) * 2019-11-11 2024-07-12 Pi工业有限公司 4- (4, 5-Dihydroisoxazol-3-yl) thiazol-2-yl) piperidine-thioimine or sulphoxide-imine derivatives and related compounds as fungicides for crop protection
CN114761403B (en) * 2019-11-11 2024-08-27 Pi工业有限公司 1- (4- (4- (5-Phenyl-4, 5-dihydro-isoxazol-3-yl) thiazol-2-yl) piperidin-1-yl) -ethan-1-one derivatives and related compounds as crop protection fungicides
WO2022130188A1 (en) 2020-12-15 2022-06-23 Pi Industries Ltd. Agrochemical composition comprising piperidine thiazole compounds
WO2022243810A1 (en) 2021-05-15 2022-11-24 Pi Industries Ltd. Novel agrochemical composition comprising piperidine thiazole compounds
WO2023007426A1 (en) 2021-07-29 2023-02-02 Pi Industries Ltd. Novel styrene compounds and a process for the preparation thereof

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