WO2009137651A2 - Fungicidal substituted azoles - Google Patents

Fungicidal substituted azoles Download PDF

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Publication number
WO2009137651A2
WO2009137651A2 PCT/US2009/043096 US2009043096W WO2009137651A2 WO 2009137651 A2 WO2009137651 A2 WO 2009137651A2 US 2009043096 W US2009043096 W US 2009043096W WO 2009137651 A2 WO2009137651 A2 WO 2009137651A2
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WO
WIPO (PCT)
Prior art keywords
imidazole
chloro
ring
methyl
difluoro
Prior art date
Application number
PCT/US2009/043096
Other languages
French (fr)
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WO2009137651A3 (en
WO2009137651A8 (en
Inventor
Thomas Paul Selby
James Francis Bereznak
John Joseph Bisaha
Amy X. Ding
Vijayagopal Gopalsamuthiram
Mary Ann Hanagan
Jeffrey Keith Long
Andrew Edmund Taggi
Original Assignee
E. I. Du Pont De Nemours And Company
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Publication date
Application filed by E. I. Du Pont De Nemours And Company filed Critical E. I. Du Pont De Nemours And Company
Priority to EP09743637A priority Critical patent/EP2274284A2/en
Priority to US12/988,888 priority patent/US20110045101A1/en
Publication of WO2009137651A2 publication Critical patent/WO2009137651A2/en
Publication of WO2009137651A8 publication Critical patent/WO2009137651A8/en
Publication of WO2009137651A3 publication Critical patent/WO2009137651A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
    • 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • 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
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/68—Halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/88—Nitrogen atoms, e.g. allantoin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
    • C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D417/02—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 two hetero rings
    • C07D417/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • This invention relates to certain azoles, their JV-oxides, salts and compositions, and methods of their use as fungicides.
  • This invention is directed to compounds of Formula 1 (including all geometric and stereoisomers), //-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides:
  • Z is N or CR 4 ;
  • Q 3 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R 5c ; or a 5- to
  • each R 5a , R 5b and R 5c is independently halogen, cyano, hydroxy, nitro, C 1 -C 7 alkyl, C 2 -C 7 alkenyl, C 2 -C 7 alkynyl, C 1 -C 7 haloalkyl, C 2 -C 7 haloalkenyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halocycloalkyl, C 4 -C 1Q alkylcycloalkyl, C 4 -C 1Q cycloalkylalkyl, C 6 -C 14 cycloalkylcycloalkyl, C 3 -C 7
  • RlO and R l 1 [ s independently H, C 1 -C 7 alkyl, C 2 -C 7 alkenyl, C 2 -C 7 alkynyl, C 1 -C 7 haloalkyl, C 2 -C 7 haloalkenyl, C 3 -C 7 cycloalkyl or C 3 -C 7 halocycloalkyl; each R 12 is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkylcarbonyl,
  • each R 13a and R 13b is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl,
  • the compound is not a compound of F-I through F-4, as shown below
  • the compound is not 4- [2-ethyl-l-(4-methoxyphenyl)-lH-imidazol-5-yl] -pyridine, 4-[l-(4-methoxyphenyl)-2-methyl-lH-imidazol-5-yl]pyridine or 3,5-dichloro-2- (4-iodo-5-phenyl-lH-l,2,3-triazol-l-yl)pyridine; and (e) when J is Q 2 , X is CR 2 , Y is N and Z is N, then R 2 is other than ⁇ . More particularly, this invention pertains to a compound of Formula 1 (including all geometric and stereoisomers), an JV-oxide or a salt thereof.
  • This invention also relates to a fungicidal composition
  • a fungicidal composition comprising a fungicidally effective amount of a compound of Formula 1 (or an JV-oxide or salt thereof) and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • This invention also relates to a fungicidal composition
  • a fungicidal composition comprising a mixture of a compound of Formula 1 (or an JV-oxide or salt thereof) and at least one other fungicide (e.g., at least one other fungicide having a different site of action).
  • This invention further relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of the invention (e.g., as a composition described herein).
  • compositions comprising, “comprising,” “includes,” “including,” “has,” “having”, “contains” or “containing” or any other variation thereof, are intended to cover a non-exclusive inclusion.
  • a composition, process, method, article, or apparatus 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, process, method, article, or apparatus.
  • “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).
  • plant includes members of Kingdom Plantae, particularly seed plants (Spermatopsida), at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature, reproductive stages (e.g., plants producing flowers and seeds). Portions of plants include geotropic members typically growing beneath the surface of the growing medium (e.g., soil), such as roots, tubers, bulbs and corms, and also members growing above the growing medium, such as foliage (including stems and leaves), flowers, fruits and seeds.
  • seedling used either alone or in a combination of words means a young plant developing from the embryo of a seed.
  • the term “broadleaf ' used either alone or in words such as “broadleaf crop” means dicot or dicotyledon, a term used to describe a group of angiosperms characterized by embryos having two cotyledons.
  • alkylating agent refers to a chemical compound in which a carbon-containing radical is bound through a carbon atom to leaving group such as halide or sulfonate, which is displaceable by bonding of a nucleophile to said carbon atom.
  • alkylating does not limit the carbon-containing radical to alkyl; the carbon-containing radicals in alkylating agents include the variety of carbon-bound substituent radicals specified, for example, for R 2 , R 3 and R 4 .
  • alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, /-propyl, or the different butyl, pentyl, hexyl or heptyl isomers.
  • Alkenyl includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl, hexenyl and heptenyl isomers.
  • Alkenyl also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl.
  • Alkynyl includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl, hexynyl and heptynyl isomers.
  • Alkynyl can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.
  • Alkylene denotes a straight-chain or branched alkanediyl.
  • alkylene examples include CH 2 , CH 2 CH 2 , CH(CH 3 ), CH 2 CH 2 CH 2 , CH 2 CH(CH 3 ) and the different butylene, pentylene and hexylene isomers.
  • Alkynylene denotes a straight-chain or branched alkynediyl containing one triple bond. Examples of “alkynylene” include CH 2 C ⁇ C, C ⁇ CCH 2 and the different butynylene, pentynylene and hexynylene isomers.
  • Alkoxy includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy, hexyloxy and heptyloxy isomers.
  • Alkylthio includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio, hexylthio and heptylthio isomers.
  • Alkylsulfmyl includes both enantiomers of an alkylsulfinyl group.
  • Alkylamino includes an NH radical substituted with straight-chain or branched alkyl. Examples of “alkylamino” include CH 3 CH 2 NH, CH 3 CH 2 CH 2 NH, and (CH 3 ) 2 CHCH 2 NH. Examples of “dialkylamino” include (CH 3 ) 2 N, (CH 3 CH 2 CH 2 ) 2 N and CH 3 CH 2 (CH 3 )N.
  • Alkoxyalkyl denotes alkoxy substitution on alkyl.
  • alkoxyalkyl examples 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 .
  • Alkylthioalkyl denotes alkylthio substitution on alkyl.
  • alkylthioalkyl examples include CH 3 SCH 2 , CH 3 SCH 2 CH 2 , CH 3 CH 2 SCH 2 , CH 3 CH 2 CH 2 CH 2 SCH 2 and CH 3 CH 2 SCH 2 CH 2 ;
  • alkylsulfmylalkyl and “alkylsulfonylalkyl” include the corresponding sulfoxides and sulfones, respectively.
  • alkylamino alkyl denotes alkylamino substitution on alkyl.
  • alkylaminoalkyl include CH 3 NHCH 2 , CH 3 NHCH 2 CH 2 , CH 3 CH 2 NHCH 2 , CH 3 CH 2 CH 2 CH 2 NHCH 2 and CH 3 CH 2 NHCH 2 CH 2 .
  • dialkylaminoalkyl include ((CH 3 ) 2 CH) 2 NCH 2 , (CH 3 CH 2 CH 2 ) 2 NCH 2 and CH 3 CH 2 (CH 3 )NCH 2 CH 2 .
  • Hydroxyalkyl denotes an alkyl group substituted with one hydroxy group. Examples of “hydroxyalkyl” include HOCH 2 CH 2 , CH 3 CH 2 (OH)CH and HOCH 2 CH 2 CH 2 CH 2 .
  • Cycloalkyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.
  • alkylcycloalkyl denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, z-propylcyclobutyl, methylcyclopentyl and methylcyclohexyl.
  • cycloalkylalkyl denotes cycloalkyl substitution on an alkyl moiety.
  • examples of “cycloalkylalkyl” include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups.
  • cycloalkylcycloalkyl denotes cycloalkyl substitution on another cycloalkyl ring, wherein each cycloalkyl ring independently has from 3 to 7 carbon atom ring members.
  • cycloalkylcycloalkyl examples include cyclopropylcyclopropyl (such as l,l'-bicyclopropyl-l-yl, 1,1'- bicyclopropyl-2-yl), cyclohexylcyclopentyl (such as 4-cyclopentylcyclohexyl) and cyclohexylcyclohexyl (such as l,l'-bicyclohexyl-l-yl), and the different cis- and trans- cycloalkylcycloalkyl isomers, (such as (li?,25)-l,l'-bicyclopropyl-2-yl and ( ⁇ R,2R)- ⁇ ,Y- bicyclopropyl-2-yl).
  • cyclopropylcyclopropyl such as l,l'-bicyclopropyl-l-yl, 1,1'- bicyclopropyl-2-yl
  • cycloalkoxy denotes cycloalkyl attached to and linked through an oxygen atom including, for example, cyclopentyloxy and cyclohexyloxy.
  • cycloalkylene denotes a cycloalkanediyl ring.
  • cycloalkylene examples include cyclopropylene, cyclobutylene, cyclopentylene and cyclohexylene.
  • cycloalkenylene denotes a cycloalkenediyl ring containing one olefmic bond.
  • Examples of “cycloalkenylene” include cylopropenediyl and cyclpentenediyl.
  • alkylene examples include CH 2 , CH 2 CH 2 , CH(CH 3 ), CH 2 CH 2 CH 2 ,
  • Trialkylsilyl includes 3 branched and/or straight-chain alkyl radicals attached to and linked through a silicon atom, such as trimethylsilyl, triethylsilyl and tert-butyldimethylsilyl.
  • halogen either alone or in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of “haloalkyl” or “alkyl substituted with halogen” include F 3 C, ClCH 2 , CF 3 CH 2 and CF 3 CCl 2 .
  • haloalkoxy examples include CF 3 O, CCl 3 CH 2 O, F 2 CHCH 2 CH 2 O and CF 3 CH 2 O.
  • haloalkylthio examples include CCl 3 S, CF 3 S, CCl 3 CH 2 S and ClCH 2 CH 2 CH 2 S.
  • halocycloalkyl examples include
  • Cj-C j The total number of carbon atoms in a substituent group is indicated by the "Cj-C j " prefix where i and j are numbers from 1 to 14.
  • C ⁇ -C 4 alkylsulfonyl designates methylsulfonyl through butylsulfonyl
  • C 2 alkoxyalkyl designates CH 3 OCH 2
  • C 3 alkoxyalkyl designates, for example, 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 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • the number of optional substituents may be restricted by an expressed limitation.
  • the phrase “optionally substituted with up to 3 substituents selected from R 5a on carbon ring members” means that 0, 1, 2 or 3 substituents can be present (if the number of potential connection points allows).
  • the phrase “optionally substituted with up to 5 substituents selected from R 5a on carbon ring members” means that 0, 1, 2, 3, 4 or 5 substituents can be present if the number of available connection points allows.
  • said substituents are independently selected from the group of defined substituents (e.g., (R v ) r wherein r is 1, 2, 3, 4 or 5 in Exhibit 1).
  • substituents are independently selected from the group of defined substituents (e.g., (R v ) r wherein r is 1, 2, 3, 4 or 5 in Exhibit 1).
  • a "ring” as a component of Formula 1 is carbocyclic or heterocyclic.
  • the term “ring system” as a component of Formula 1 denotes two fused rings (e.g., two phenyl rings fused to form naphthalenyl).
  • nonaromatic includes rings that are fully saturated as well as partially or fully unsaturated, provided that none of the rings are aromatic.
  • a "fully unsaturated heterocycle” includes both aromatic and nonaromatic heterocycles.
  • aromatic indicates that each of the ring atoms of a fully unsaturated ring is essentially in the same plane and has a /?-orbital perpendicular to the ring plane, and that (4n + T) ⁇ electrons, where n is a positive integer, are associated with the ring to comply with H ⁇ ckel's rule.
  • carbocyclic ring denotes a ring or ring system wherein the atoms forming the ring backbone are selected only from carbon.
  • a carbocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring.
  • saturated carbocyclic refers to a ring having a backbone consisting of carbon atoms linked to one another by single bonds; unless otherwise specified, the remaining carbon valences are occupied by hydrogen atoms.
  • heterocyclic ring or “heterocycle” denote a ring in which at least one atom forming the ring backbone is not carbon (e.g., N, O or S). Typically a heterocyclic ring contains no more than 4 N atoms, no more than 2 O atoms and no more than 2 S atoms. Unless otherwise indicated, a heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. When a fully unsaturated heterocyclic ring satisfies H ⁇ ckel's rule, then said ring is also called a "heteroaromatic ring” or “aromatic heterocyclic ring”.
  • heterocyclic ring system or “heteroaromatic bicyclic ring system” denote a ring system in which at least one atom forming the ring backbone is not carbon (e.g., N, O or S) and at least one ring is aromatic. Unless otherwise indicated, heterocyclic rings and heteroaromatic ring systems can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
  • substituents are optional, 0 to 5 substituents may be present, limited only by the number of available points of attachment.
  • the ring members selected from up to 2 O, up to 2 S and up to 4 N atoms are optional, provided at least one ring member is not carbon (e.g., N, O or S).
  • the nitrogen atom ring members may be oxidized as //-oxides, because compounds relating to Formula 1 also include iV-oxide derivatives.
  • Examples of a 5- to 6-membered fully unsaturated heterocyclic ring include the rings A-I through A-31 illustrated in Exhibit 1, and examples of an 8- to 10-membered heteroaromatic bicyclic ring system include the ring systems A-31 through A-72 illustrated in Exhibit 2.
  • the relative the variable (R v ) r is any substituent as defined in the Summary of the Invention for Q 1 , Q 2 and Q 3 (e.g., a Q 1 ring or ring system is optionally substituted with R 5a on carbon ring members and cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminoalkyl and C 3 -C 6 dialkylaminoalkyl on nitrogen atom ring members) and r is an integer from 0 to 5, limited by the number of available positions on each depicted ring or ring system.
  • substituents are optional, 0 to 5 substituents may be present, limited only by the number of available points of attachment.
  • the ring members selected from up to 2 O, up to 2 S and up to 4 N atoms are optional, provided at least one ring member is not carbon (e.g., N, O or S).
  • the nitrogen atom ring members may be oxidized as iV-oxides, because compounds relating to Formula 1 also include iV-oxide derivatives.
  • Examples of a 5- to 6-membered fully unsaturated heterocyclic ring in W 1 , W 2 and W 3 include the rings A-I through A-31 illustrated in Exhibit 1 wherein (R v ) r is any substituent as defined in the Summary of the Invention for W 1 , W 2 or W 3 (e.g., a W 1 ring is optionally substituted with R 5a on carbon ring members and cyano, C j -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminoalkyl and C 3 -C 6 dialkylaminoalkyl on nitrogen atom ring members) and r is an integer from 0 to 5, limited
  • R v groups are shown in the structures A-I through A-72, it is noted that they do not need to be present since they are optional substituents. Note that when R v is H attached to an atom, this is the same as if said atom is unsubstituted. The nitrogen atoms that require substitution to fill their valence are substituted with H or R v . Note that when the attachment point between (R v ) r and the depicted ring or ring system is illustrated as floating, (R v ) r can be attached to any available carbon atom or nitrogen atom of the depicted ring or ring system.
  • the depicted ring or ring system can be attached to the remainder of Formula 1 through any available carbon or nitrogen of the depicted ring or ring system by replacement of a hydrogen atom.
  • Compounds of this invention can exist as one or more stereoisomers.
  • the various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers.
  • one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers.
  • the compounds of the invention may be present as a mixture of stereoisomers or as individual stereoisomers (e.g., in optically active form).
  • Atropisomers which are conformational isomers that occur when rotation about a single bond in a molecule is restricted as a result of steric interaction with other parts of the molecule and the substituents at both ends of the single bond are unsymmetrical.
  • atropisomerism occurs at a single bond in Formula 1 when the rotational barrier is high enough (about ⁇ G > 25 kcal moH) that separation of isomers at ambient temperature becomes possible.
  • one atropisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other atropisomer or when separated from the other atropisomer.
  • Atropisomers can be found in March, Advanced Organic Chemistry, 4th Ed. 1992, 101-102 and Gawronski et al, Chirality 2002, 14, 689-702.
  • This invention includes compounds or compositions that are enriched in an atropisomer of Formula 1 compared to other atropisomers of the compounds. Also included are the essentially pure atropisomers of compounds of Formula 1.
  • nitrogen-containing heterocycles can form JV-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen-containing heterocycles which can form TV-oxides.
  • tertiary amines can form JV-oxides.
  • Synthetic methods for the preparation of iV-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane.
  • MCPBA peroxy acids
  • alkyl hydroperoxides such as t-butyl hydroperoxide
  • sodium perborate sodium perborate
  • dioxiranes such as dimethyldioxirane.
  • salts of the compounds of Formula 1 are useful for control of plant diseases caused by fungal plant pathogens (i.e. are agriculturally suitable).
  • the salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
  • the present invention comprises compounds selected from Formula 1, JV-oxides and agriculturally suitable salts thereof.
  • 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.
  • a polymorph of a compound represented by Formula 1 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 represented by Formula 1.
  • Preparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.
  • Embodiments of the present invention as described in the Summary of the Invention include those described below.
  • Formula 1 includes iV-oxides and salts thereof, and reference to "a compound of Formula 1" includes the definitions of substituents specified in the Summary of the Invention unless further defined in the
  • Embodiment 1 A compound of Formula 1 wherein J is Q 2 .
  • Embodiment 2. A compound of Formula 1 wherein J is R 1 .
  • Embodiment 3 A compound of Formula 1 or Embodiment 2 wherein R 1 is C 1 -C 3 alkyl.
  • Embodiment 4 A compound of Embodiment 3 wherein R 1 is methyl.
  • Embodiment 5 A compound of Formula 1 or any one of Embodiments 1 through 4 wherein X is CR 2 or CQ 3 .
  • Embodiment 6 A compound of Embodiment 5 wherein X is CR 2 .
  • Embodiment 6a A compound of Embodiment 5 wherein X is CQ 3 .
  • Embodiment 7. A compound of Formula 1 or any one of Embodiments 1 through 6a wherein Y is N.
  • Embodiment 8. A compound of Formula 1 or any one of Embodiments 1 through 6a wherein Y is CR 3 .
  • Embodiment 9 A compound of Formula 1 or any one of Embodiments 1 through 8 wherein Z is CR 4 .
  • Embodiment 10 A compound of Formula 1 or any one of Embodiments 1 through 8 wherein Z is N.
  • Embodiment 11 A compound of Formula 1 wherein J is Q 2 , X is CR 2 , Y is N and Z is CR 4 , or J is R 1 , X is CQ 3 , Y is CR 3 and Z is N, or J is Q 2 , X is CR 2 , Y is N and Z is N.
  • Embodiment 12 A compound of Embodiment 11 wherein J is Q 2 , X is CR 2 , Y is N and Z is CR 4 or J is R 1 , X is CQ 3 , Y is CR 3 and Z is N.
  • Embodiment 13 A compound of Embodiment 12 wherein J is Q 2 , X is CR 2 , Y is N and
  • Embodiment 15 A compound of Embodiment 14 wherein Q 1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R 5a on carbon atom ring members and selected from cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl,
  • Embodiment 16 A compound of Embodiment 15 wherein Q 1 is a phenyl or pyridinyl ring, optionally substituted with up to 3 substituents independently selected from
  • Embodiment 17 A compound of Embodiment 16 wherein Q 1 is a pyridinyl ring attached to Formula 1 at the 3 -position of the pyridinyl ring and optionally substituted with up to 3 substituents independently selected from R 5a .
  • Embodiment 18 A compound of Embodiment 16 wherein Q 1 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 5a .
  • Embodiment 19 A compound of Embodiment 16 wherein Q 1 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 5a .
  • Embodiment 20 A compound of Embodiment 19 wherein W 1 is a phenyl or
  • Embodiment 21 A compound of Embodiment 20 wherein W 1 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 5a .
  • Embodiment 23 A compound of Embodiment 22 wherein Q 2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R 5 ⁇ on carbon atom ring members and selected from cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminoalkyl and C 3 -C 6 dialkylaminoalkyl on nitrogen atom ring members; or C(R 7a R 7
  • Embodiment 24 A compound of Embodiment 23 wherein Q 2 is a phenyl or pyridinyl ring, optionally substituted with up to 3 substituents independently selected from R5b.
  • Embodiment 25 A compound of Embodiment 24 wherein Q 2 is a pyridinyl ring attached to Formula 1 at the 3 -position of the pyridinyl ring and optionally substituted with up to 3 substituents independently selected from R 5 ⁇ .
  • Embodiment 26 A compound of Embodiment 24 wherein Q 2 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 5 ⁇ .
  • Embodiment 27 A compound of Embodiment 24 wherein Q 2 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 5 ⁇ .
  • Embodiment 27a A compound of Formula 1 or any one of Embodiments 1 through 27 wherein when each Q 1 and Q 2 is independently a phenyl or pyridinyl ring, then one of the Q 1 and Q 2 rings is substituted with 2 or 3 substituents and the other of the Q 1 and Q 2 rings is substituted with 1 or 2 substituents.
  • Embodiment 28 A compound of Formula 1 or any one of Embodiments 1 through 27 wherein at least one R 5a substituent is attached at an ortho position of the Q 1 ring.
  • Embodiment 29 A compound of Formula 1 or any one of Embodiments 1 through 28 wherein two R 5a substituents are attached at ortho positions of the Q 1 ring.
  • Embodiment 30 A compound of Formula 1 or any one of Embodiments 1 through 29 wherein at least one R 5 ⁇ substituent is attached at an ortho position of the Q 2 ring.
  • Embodiment 31 A compound of Formula 1 or any one of Embodiments 1 through 30 wherein two R 5 ⁇ substituents are attached at ortho positions of the Q 2 ring.
  • Embodiment 32 A compound of Formula 1 or any one of Embodiments 1 through 23 wherein W 2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R 5 b on carbon atom ring members and selected from cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminoalky
  • Embodiment 33 A compound of Embodiment 32 wherein W 2 is a phenyl or pyridinyl ring, optionally substituted with up to 3 substituents independently selected from R5b.
  • Embodiment 34 A compound of Embodiment 33 wherein W 2 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 5 ⁇ .
  • Embodiment 35 A compound of Embodiment 32 wherein W 2 is a phenyl or pyridinyl ring, optionally substituted with up to 3 substituents independently selected from R 5 ⁇ .
  • Embodiment 36 A compound of Embodiment 35 wherein Q 3 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R 5c on carbon atom ring members and selected from cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminoalkyl and C 3 -C 6 dialkylaminoalkyl on nitrogen atom ring members; or C(R 7a R 7b
  • Embodiment 37 A compound of Embodiment 36 wherein Q 3 is a phenyl or pyridinyl ring, optionally substituted with up to 3 substituents independently selected from R5c.
  • Embodiment 38 A compound of Embodiment 37 wherein Q 3 is a pyridinyl ring attached to Formula 1 at the 3 -position of the pyridinyl ring and optionally substituted with up to 3 substituents independently selected from R 5c .
  • Embodiment 39 A compound of Embodiment 37 wherein Q 3 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 5c .
  • Embodiment 40 Embodiment 40.
  • Embodiment 41 A compound of Embodiment 40 wherein W 3 is a phenyl or pyridinyl ring, optionally substituted with up to 3 substituents independently selected from R 5C .
  • Embodiment 42 A compound of Embodiment 41 wherein W 3 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 5c .
  • Embodiment 44 A compound of Embodiment 43 wherein each R 2 , R 3 and R 4 is independently H, halogen, cyano or C 1 -C 3 alkyl.
  • Embodiment 45 A compound of Embodiment 44 wherein each R 2 , R 3 and R 4 is independently Cl, Br, I or C 1 -C 2 alkyl.
  • Embodiment 46 A compound of Embodiment 45 wherein each R 2 , R 3 and R 4 is independently Cl, Br or methyl.
  • Embodiment 47 A compound of Formula 1 or any one of Embodiments 1 through 46 wherein each R 5a , R 5 ⁇ and R 5c is independently halogen, cyano, C 1 -C 3 alkyl,
  • Embodiment 48 A compound of Embodiment 47 wherein each R 5a , R 5 ⁇ and R 5c is independently halogen, cyano, C 1 -C 3 alkyl, C 2 -C 3 alkenyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio or C 1 -C 3 alkylamino.
  • Embodiment 49 A compound of Embodiment 48 wherein each R 5a , R 5 ⁇ and R 5c is independently halogen, cyano, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl or C 1 -C 3 alkoxy.
  • Embodiment 50 A compound of Embodiment 49 wherein each R 5a , R 5 ⁇ and R 5c is independently F, Cl, Br, cyano, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl or C 1 -C 2 alkoxy.
  • Embodiment 51 A compound of Embodiment 48 wherein each R 5a , R 5 ⁇ and R 5c is independently halogen, cyano, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl or C 1 -C 3 alkoxy.
  • Embodiment 52. A compound of Formula 1 or any one of Embodiments 1 through 47 wherein each U is independently O or NR 12 .
  • Embodiment 53 A compound of Embodiment 52 wherein each U is independently O or NH.
  • Embodiment 54 A compound of Formula 1 or any one of Embodiments 1 through 47 wherein each V is C 2 -C 4 alkylene.
  • Embodiment 55 A compound of Formula 1 or any one of Embodiments 1 through 47 wherein each T is independently NR 13a R 13b or OR 14 .
  • Embodiment 55 a A compound of Formula 1 or any one of Embodiments 1 through 55 wherein each R 13a and R 13 ⁇ is independently H, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl.
  • Embodiment 55b A compound of Formula 1 or any one of Embodiments 1 through 55 wherein each R 13a and R 13 ⁇ is independently H, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl.
  • Embodiment 56 A compound of Formula 1 or any one of Embodiments 1 through 55b independently when an instance of R 7a is not taken together with the carbon atom to which the instance of R 7a is attached and a geminal instance of R 7 ⁇ to form a carbocyclic ring (i.e. R 7a is taken alone) then the instance of R 7a is H, cyano or methyl.
  • Embodiment 56a A compound of Embodiment 56 wherein each R 7a is independently H or methyl.
  • Embodiment 57 A compound of Embodiment 56a wherein each R 7a is H.
  • Embodiment 58 A compound of Formula 1 or any one of Embodiments 1 through 57 wherein independently when an instance of R 7 ⁇ is not taken together with the carbon atom to which the instance of R 7 ⁇ is attached and a geminal instance of R 7a to form a carbocyclic ring (i.e. R 7 ⁇ is taken alone) then the instance of R 7 ⁇ is independently H or methyl.
  • Embodiment 59 A compound of Embodiment 58 wherein each R 7 ⁇ is H.
  • Embodiment 59a A compound of Formula 1 or any one of Embodiments 1 through 59 wherein when a pair of R 7a and R 7 ⁇ attached to the same carbon atom are taken together with the carbon atom to form a carbocyclic ring, the ring is a cyclopropyl ring.
  • Embodiment 60 A compound of Formula 1 or any one of Embodiments 1 through 59a wherein each pair of R 7a and R 7 ⁇ attached to the same carbon atom are not taken together to form a carbocyclic ring (i.e. R 7a and R 7 ⁇ are taken alone).
  • Embodiment 61 A compound of Formula 1 or any one of Embodiments 1 through 60 wherein each R 8 , R 9a , R 9b , R 10 and R 11 is independently H, C 1 -C 2 alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl or C 1 -C 2 haloalkyl.
  • Embodiment 62 A compound of Embodiment 61 wherein each R 8 , R 9a , R 9 ⁇ , R l ° and
  • R 1 * is independently H or methyl.
  • Embodiment 63a A compound of Formula 1 or any one Embodiments 1 through 62 wherein when J is Q 2 , X is CR 2 , Y is N and Z is CR 4 and Q 1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R 5a ; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2
  • R 4 is halogen and Q 2 is a phenyl ring or 2-pyridinyl ring substituted with halogen at an ortho position, then said phenyl ring or 2-pyridinyl ring is also substituted with R 5 ⁇ at a meta position.
  • Embodiment 64a A compound of Formula 1 or any one Embodiments 1 through 62 wherein when J is Q 2 , X is CR 2 , Y is N and Z is CR 4 and Q 2 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R 5b ; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2
  • Embodiment 65 A compound of Formula 1 or any one of Embodiments 1 through 62 wherein when J is Q 2 , X is CR 2 , Y is N and Z is CR 4 , then
  • Embodiment 65 a A compound of Formula 1 of Embodiment 65 wherein when R 2 is halogen and Q 1 is a phenyl ring substituted with halogen at an ortho position, then Q 2 is neither phenyl nor substituted phenyl; and when R 4 is halogen and Q 2 is a phenyl ring substituted with halogen at an ortho position, then Q 1 is neither phenyl nor substituted phenyl.
  • Embodiments of this invention can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds useful for preparing the compounds of Formula 1.
  • embodiments of this invention including Embodiments l-65a above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention.
  • Embodiment Al Combinations of Embodiments l-65a are illustrated by: Embodiment Al .
  • Q 1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R 5a ; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from up to 2 O, up to 2 S and up to
  • W 1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R 5a on carbon atom ring members and selected from cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminoalkyl and C 3 -C 6 dialkylaminoalkyl on nitrogen atom ring members;
  • W 2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R 5b on carbon atom ring members and selected from cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminoalkyl and C 3 -C 6 dialkylaminoalkyl on nitrogen atom ring members;
  • Q 3 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents
  • W 3 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R 5c on carbon atom ring members and selected from cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C
  • Q 1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R 5a on carbon atom ring members and selected from cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminoalkyl and C 3 -C 6 dialkylaminoalkyl on nitrogen atom ring members; or C(R 7a R 7b )W ! ;
  • W 1 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R 5a ;
  • Q 2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R 5b on carbon atom ring members and selected from cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminoalkyl and C 3 -C 6 dial
  • W 2 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R 5b ;
  • Q 3 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R 5c on carbon atom ring members and selected from cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminoalkyl and C 3 -C 6 dial
  • each R 5a , R 5b and R 5c is independently halogen, cyano, C 1 -C 3 alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, C 1 -C 3 haloalkyl, C 3 cycloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkoxy, C 1 -C 3 alkylthio, C 1 -C 3 alkylamino, C 2 -C 4 dialkylamino C 2 -C 4 alkylcarbonyl, C 2 -C 4 alkoxycarbonyl, C 2 -C 4 alkylcarbonylamino or -U-V-T;
  • U is O or NH;
  • V is C 2 -C 4 alkylene;
  • T is NR 13a R 13b or OR 14 ;
  • each R 7a and R 7b is independently H or methyl; each R 8 , R 9a , R 9b
  • Embodiment A3 A compound of Embodiment A2 wherein Q 1 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R 5a ; Q 2 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R 5b ; and Q 3 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R 5c .
  • Embodiment A4 A compound of Embodiment A3 wherein each R 2 , R 3 and R 4 is independently H, halogen, cyano or C 1 -C 3 alkyl; and each R 5a , R 5b and R 5c is independently halogen, cyano, C 1 -C 3 alkyl, C 2 -C 3 alkenyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio or C 1 -C 3 alkylamino.
  • Embodiment A5 A compound of Embodiment A4 wherein J is Q 2 ; X is CR 2 ; Y is N;
  • Z is CR 4 ; each R 2 and R 4 is independently Cl, Br, I or C 1 -C 2 alkyl; each R 5a and R 5b is independently F, Cl, Br, cyano, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl or C 1 -C 2 alkoxy; and one of the Q 1 and Q 2 rings is substituted with 2 to 3 substituents and the other of the Q 1 and Q 2 rings is substituted with 1 to 2 substituents.
  • Specific embodiments include compounds of Formula 1 selected from the group consisting of:
  • Another aspect of the present invention relates to compounds of Formula IP (including all geometric and stereoisomers), iV-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides:
  • X is N, CR 2 Or CQ 3 ;
  • Y is N or CR 3 ;
  • Z is N or CR 4 ;
  • Q 1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R 5a ;
  • Q 2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R 5b ;
  • Q 3 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R 5c ;
  • R 1 is C 1 -C 7 alkyl, C 2 -C 7 alkenyl, C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 7 haloalkyl, C 2 -C 7 haloalkenyl, C ⁇ C 1Q alkylcycloalkyl or C ⁇ C 1Q cycloalkylalkyl; each R 2 , R 3 and R 4 is independently ⁇ , halogen, cyano, nitro, C 1 -C 7 alkyl, C 2 -C 7 alkenyl, C 7 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 7 haloalkyl, C 2 -C 7 haloalkenyl, C 1 -C 7 alkoxy, C 1 -C 7 haloalkoxy, C 1 -C 7 alkylthio, C 1 -C 7 alkylsulfmyl,
  • this aspect of the present invention pertains to a compound of Formula IP (including all geometric and stereoisomers), an JV-oxide or a salt thereof.
  • a fungicidal composition comprising (a) a compound selected from Formula IP, //-oxides and salts thereof; and (b) at least one other fungicide. Also related to this aspect is a fungicidal composition comprising (a) a fungicidally effective amount of a compound selected from Formula IP, //-oxides and salts thereof; and (b) at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • Also related to this aspect is a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound selected from Formula IP, JV-oxides and salts thereof (e.g., as a composition described herein).
  • Embodiments of this aspect include Embodiments Bl through B53 described below.
  • Formula IP includes iV-oxides and salts thereof, and reference to "a compound of Formula IP" includes the definitions of substituents specified above for Formula IP unless further defined in the Embodiments.
  • Embodiment B 1. A compound of Formula IP wherein J is Q 2 .
  • Embodiment B2. A compound of Formula IP wherein J is R 1 .
  • Embodiment B3. A compound of Formula IP or Embodiment Bl wherein R 1 is C 1 -C 2 alkyl.
  • Embodiment B4 A compound of Formula IP wherein X is CR 2 .
  • Embodiment B5. A compound of Formula IP wherein X is CQ 3 .
  • Embodiment B6. A compound of Formula IP wherein Y is N.
  • Embodiment B7 A compound of Formula IP wherein Y is CR 3 .
  • Embodiment B8. A compound of Formula IP wherein Z is CR 4 .
  • Embodiment B9. A compound of Formula IP wherein Z is N.
  • Embodiment BlO. A compound of Formula IP wherein Q 1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R 5a .
  • Q 2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R 5 ⁇ .
  • Embodiment B 13 A compound of Embodiment BlO wherein Q 1 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 5a .
  • Embodiment B 14 A compound of Embodiment BI l wherein Q 2 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 5 ⁇ Embodiment B 15.
  • Embodiment B 16 A compound of Embodiment B13 wherein Q 1 is a phenyl ring optionally substituted with up to 2 substituents independently selected from R 5a .
  • Embodiment B 17. A compound of Embodiment B 14 wherein Q 2 is a phenyl ring optionally substituted with up to 2 substituents independently selected from R 5 ⁇ .
  • Embodiment B 18 A compound of Embodiment B15 wherein Q 3 is a phenyl ring optionally substituted with up to 2 substituents independently selected from R 5c .
  • Embodiment B 19 A compound of Embodiment B16 wherein Q 1 is a phenyl ring optionally substituted with up to 1 substituent selected from R 5a .
  • Embodiment B20. A compound of Embodiment B17 wherein Q 2 is a phenyl ring optionally substituted with up to 1 substituent selected from R 5 ⁇ .
  • Embodiment B21. A compound of Embodiment Bl 8 wherein Q 3 is a phenyl ring optionally substituted with up to 1 substituent selected from R 5c .
  • Embodiment B22 A compound of Formula IP or Embodiment B13 wherein Q 1 is a phenyl ring substituted with up to 3 substituents independently selected from R 5a attached at ortho and/or para positions.
  • Embodiment B23 A compound of Formula IP or Embodiment B 14 wherein Q 2 is a phenyl ring substituted with up to 3 substituents independently selected from R 5b attached at ortho and/or para positions.
  • Embodiment B24 A compound of Formula IP or Embodiment B 15 wherein Q 3 is a phenyl ring substituted with up to 3 substituents independently selected from R 5c attached at ortho and/or para positions.
  • Embodiment B25 A compound of Formula IP or Embodiment B22 wherein Q 1 is a phenyl ring substituted with 3 substituents independently selected from R 5a attached at ortho and para positions.
  • Embodiment B26 A compound of Formula IP or Embodiment B23 wherein Q 2 is a phenyl ring substituted with 3 substituents independently selected from R 5b attached at ortho and para positions.
  • Embodiment B27 A compound of Formula IP or Embodiment B24 wherein Q 3 is a phenyl ring substituted with 3 substituents independently selected from R 5c attached at ortho and para positions.
  • Embodiment B28 A compound of Formula IP or Embodiment B22 wherein Q 1 is a phenyl ring substituted with up to 2 substituents independently selected from R 5a attached at ortho and/or para positions.
  • Embodiment B29 A compound of Formula IP or Embodiment B23 wherein Q 2 is a phenyl ring substituted with up to 2 substituents independently selected from R 5b attached at ortho and/or para positions.
  • Embodiment B30 A compound of Formula IP or Embodiment B24 wherein Q 3 is a phenyl ring substituted with up to 2 substituents independently selected R 5c attached at ortho and/or para positions.
  • Embodiment B31 A compound of Formula IP or Embodiment B28 wherein Q 1 is a phenyl ring substituted with 2 substituents independently selected from R 5a attached at one ortho position and the para position.
  • Embodiment B32 A compound of Formula IP or Embodiment B29 wherein Q 2 is a phenyl ring substituted with 2 substituents independently selected from R 5b attached at one ortho position and the para position.
  • Embodiment B33 A compound of Formula IP or Embodiment B30 wherein Q 3 is a phenyl ring substituted with 2 substituents independently selected from R 5c attached at one ortho position and the para position.
  • Embodiment B34 A compound of Formula IP or Embodiment B28 wherein Q 1 is a phenyl ring substituted with 2 substituents independently selected from R 5a attached at ortho positions.
  • Embodiment B35 A compound of Formula IP or Embodiment B29 wherein Q 2 is a phenyl ring substituted with 2 substituents independently selected from R 5 ⁇ attached at ortho positions.
  • Embodiment B36 A compound of Formula IP or Embodiment B30 wherein Q 3 is a phenyl ring substituted with 2 substituents independently selected from R 5c attached at ortho positions.
  • Embodiment B37 A compound of Formula IP wherein Q 1 is a phenyl ring substituted with 2 substituents independently selected from R 5a attached at one meta position and the para position.
  • Embodiment B38 A compound of Formula IP wherein Q 2 is a phenyl ring substituted with 2 substituents independently selected from R 5 ⁇ attached at one meta position and the para position.
  • Embodiment B39 A compound of Formula IP wherein Q 3 is a phenyl ring substituted with 2 substituents independently selected from R 5c attached at one meta position and the para position.
  • Embodiment B40 A compound of Formula IP or Embodiment B 19 wherein Ql is a phenyl ring substituted with up to 1 substituent selected from R 5a attached at the para position.
  • Embodiment B41 A compound of Formula IP or Embodiment B21 wherein Q ⁇ is a phenyl ring substituted with up to 1 substituent selected from R 5c attached at the para position.
  • Embodiment B42 A compound of Formula IP or Embodiment B40 wherein Q 1 is a phenyl ring substituted with 1 substituent selected from R 5a attached at the para position.
  • Embodiment B43 A compound of Formula IP or Embodiment B40 wherein Q 1 is a phenyl ring substituted with 1 substituent selected from R 5a attached at the para position.
  • Embodiment B44. A compound of Formula IP or Embodiment B41 wherein Q 3 is a phenyl ring substituted with 1 substituent selected from R 5c attached at the para position.
  • Embodiment B45. A compound of Formula IP wherein each R 2 , R 3 and R 4 is independently H, halogen, cyano, C 1 -C 3 alkyl, C 2 -C 3 alkenyl, C 3 cycloalkyl or C 1 -C 3 haloalkyl.
  • Embodiment B46 A compound of Embodiment B45 wherein each R 2 , R 3 and R 4 is independently H, halogen or C 1 -C 3 alkyl.
  • Embodiment B47 A compound of Embodiment B46 wherein each R 2 , R 3 and R 4 is independently H, Cl, Br, I or C 1 -C 2 alkyl.
  • Embodiment B48 A compound of Embodiment B47 wherein R 2 is selected from H, Cl,
  • Embodiment B49 A compound of Embodiment B47 wherein R 3 is selected from H, Cl,
  • Embodiment B50 A compound of Embodiment B47 wherein R 4 is selected from H, Cl,
  • Embodiment B51 A compound of Formula IP wherein each R 5a , R 5 ⁇ and R 5c is independently halogen, cyano, nitro, C 1 -C 3 alkyl, C 2 -C 3 alkenyl, C 3 cycloalkyl,
  • C 1 -C 3 haloalkyl C 2 -C 3 haloalkenyl, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3 haloalkylthio, C 1 -C 3 haloalkoxy or C 1 -C 6 haloalkylthio.
  • Embodiment B52 A compound of Embodiment B51 wherein each R 5a , R 5 ⁇ and R 5c is independently halogen, cyano, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl or C 1 -C 3 alkoxy.
  • Embodiment B53 A compound of Embodiment B52 wherein each R 5a , R 5 ⁇ and R 5c is independently halogen, CH 3 , OCH 3 or CF 3 .
  • Embodiments B1-B53 above as well as any other embodiments described herein relevant to Formula IP can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula IP but also to the starting compounds and intermediate compounds useful for preparing the compounds of Formula IP.
  • Embodiments B1-B53 above as well as any other embodiments described herein relevant to Formula IP, and any combination thereof pertain to the compositions and methods relating to compounds of Formula IP.
  • counterparts of Embodiments 1- 62 wherein "Formula 1" is replaced by "Formula IP” to the extent that these counterpart embodiments limit the definition of substituents on Formula IP.
  • counterparts of Embodiments B1-B53 wherein "Formula IP” is replaced by "Formula 1" to the extent that these counterpart embodiments limit the definition of substituents on Formula 1.
  • Embodiment Cl A compound of Formula IP wherein
  • Q 1 is independently a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R 5a ;
  • Q 2 is independently a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R 5 b;
  • Q 3 is independently a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with
  • each R 5a , R 5 ⁇ and R 5c is independently halogen, cyano, nitro, C 1 -C 7 alkyl, C 2 -C 7 alkenyl, C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 7 haloalkyl,
  • Embodiment C3 A compound of Embodiment C2 wherein each R 2 and R 4 is independently H, halogen, cyano, C 1 -C 3 alkyl, C 2 -C 3 alkenyl, C 3 cycloalkyl or C 1 -C 3 haloalkyl; and each R 5a and R 5 ⁇ is independently halogen, cyano, nitro, C 1 -C 3 alkyl, C 2 -C 3 alkenyl, C 3 cycloalkyl, C 1 -C 3 haloalkyl, C 2 -C 3 haloalkenyl, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3 haloalkylthio, C 1 -C 3 haloalkoxy or
  • Embodiment C4 A compound of Embodiment C3 wherein
  • Q 1 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 5a;
  • Q 2 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R 5 ⁇ ;
  • each R 2 and R 4 is independently H, halogen or C 1 -C 3 alkyl;
  • each R 5a and R 5b is independently halogen, cyano, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl or C 1 -C 3 alkoxy.
  • each R 2 and R 4 is independently H, Cl, Br, I or C 1 -C 2 alkyl; and each R 5a and R 5b is independently halogen, CH 3 , OCH 3 or CF 3 .
  • Embodiment C7 A compound of Embodiment Cl wherein X is CQ 3 ; Y is CR 3 ;
  • R 3 is H, Cl, Br or CH 3 ; Z is N;
  • R 1 is C 1 -C 2 alkyl.
  • compounds of Formula 1 or Formula IP including geometric and stereoisomers, iV-oxides, and salts thereof (including but not limited to Embodiments 1-62, A1-A5, Bl-53 and C1-C6, above) wherein when Q 1 is a phenyl ring which is not substituted by R 5a at either ortho positions, then when X is N or CR 2 and Q 2 is a phenyl ring, the Q 2 phenyl ring is substituted by at least one R 5 * 5 at an ortho position.
  • This invention provides a fungicidal composition
  • a fungicidal composition comprising a compound of Formula 1 or Formula IP (including all geometric and stereoisomers, iV-oxides, and salts thereof), and at least one other fungicide.
  • a compound of Formula 1 or Formula IP including all geometric and stereoisomers, iV-oxides, and salts thereof
  • at least one other fungicide are compositions comprising a compound corresponding to any of the compound embodiments described above.
  • This invention provides a fungicidal composition
  • a fungicidal composition comprising a fungicidally effective amount of a compound of Formula 1 or Formula IP (including all geometric and stereoisomers, iV-oxides, and salts thereof), and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • a compound of Formula 1 or Formula IP including all geometric and stereoisomers, iV-oxides, and salts thereof
  • additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • This invention provides a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula 1 or Formula IP (including all geometric and stereoisomers, iV-oxides, and salts thereof).
  • a compound of Formula 1 or Formula IP including all geometric and stereoisomers, iV-oxides, and salts thereof.
  • embodiment of such methods are methods comprising applying a fungicidally effective amount of a compound corresponding to any of the compound embodiments describe above.
  • the compounds are applied as compositions of this invention.
  • Compounds of Formula Ia (Formula 1 wherein J is Q 2 , X is CR 2 , Y is N and Z is CR 4 ) can be prepared by halogenation or alkylation of compounds of Formula Ib (i.e. Formula 1 wherein J is Q 2 , X is CR 2 , R 2 is H, Y is N and Z is CR 4 ) as illustrated in Scheme 1.
  • halogenation can be achieved using a variety of halogenating reagents known in the art such as elemental halogen (e.g., CI 2 , Br 2 , I 2 ), sulfuryl chloride, iodine monochloride or a JV-halosuccinimide (e.g., NBS, NCS, NIS) in an appropriate solvent such as ⁇ /, ⁇ /-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane or acetic acid.
  • elemental halogen e.g., CI 2 , Br 2 , I 2
  • sulfuryl chloride iodine monochloride
  • iodine monochloride iodine monochloride
  • JV-halosuccinimide e.g., NBS, NCS, NIS
  • Alkylation is achieved by reacting a compound of Formula Ib with a metalating agent, followed by an alkylating agent of formula R 2 -Lg (wherein Lg is a leaving group such as Cl, Br, I or a sulfonate, for example, /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate).
  • Suitable metalating agents include, for example, as n-butyl lithium (n-BuL ⁇ ), lithium diisopropylamide (LDA) or sodium hydride (NaH).
  • alkylation and “alkylating agent” are not limited to R 2 being an alkyl group, and include in addition to alkyl such groups as alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like.
  • alkyl such groups as alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like.
  • alkyl such groups as alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like.
  • Compounds of Formula Ia can be subjected to various nucleophilic and metallation reactions to add substituents or modify existing substituents, and thus provide other functionalized compounds of Formula Ia.
  • compounds of Formula Ia wherein R 2 and/or R 4 are halogen can undergo nucleophilic displacements to provide compounds of Formula Ia wherein R 2 and/or R 4 are groups linked to the imidazole ring through an O, S or N atom (e.g., displacements with alkoxides, thiolates and amines).
  • compounds of Formula Ia wherein R 2 and/or R 4 are iodo can be used to prepare the corresponding thiocyanate (-SCN) derivatives of Formula Ia.
  • Typical conditions involve contacting the iodo compound of Formula Ia with a thiocyanating agent such as K[Cu(SCN) 2 ], which is generated in situ from equimolar amounts of copper(I) thiocyanate and potassium thiocyanate.
  • the reaction is typically carried out in a polar solvent such as ⁇ /, ⁇ /-dimethylformamide, dimethylacetamide, 1,4-dioxane or dimethylsulfoxide at a temperature between about room temperature and the reflux temperature of the solvent.
  • the reaction can also be carried out at higher temperatures using a microwave reactor.
  • Suzuki et al. Synthetic Communications 1996, 2(5(18), 3413- 3419.
  • compounds of Formula Ia wherein R 2 and/or R 4 are bromo or iodo can be cross-coupled with compounds of formulae R 2 -Met or R 4 -Met (wherein Met is Sn, Zn, B(OH) 2 , Mg, Li, Cu or other suitable counterions) in the presence of a palladium or nickel catalyst to produce compounds of Formula Ia wherein R 2 and/or R 4 are cyano, alkyl, alkenyl, haloalkenyl, alkynyl, and the like.
  • Preferred catalysts include but are not limited to Pd(PPh 3 ) 4 , PdCl 2 (PPh 3 ) 2 , PdCl 2 (diphenylphosphinoferrocene), NiCl 2 (PPh 3 ) 2 and tetrakis(tri-2-furylphosphino)palladium.
  • the exact conditions for each reaction will depend upon the catalyst used and the counterions in the compound of formulae R 2 -Met or R 4 -Met.
  • the presence of a base (such as an alkali carbonate, tertiary amine or alkali fluoride) is necessary for reactions involving compounds of formulae R 2 -Met or R 4 -Met where Met is B(OH) 2 .
  • Examples 13, 16, 17, 18, 19 and 31 illustrate various cross-coupling reactions for the preparation of certain compounds of Formula Ia.
  • compounds of Formula Ia can alternatively be prepared by halogenation of a compound of Formula 2 preferentially at the 4-position of the imidazole ring to provide a compound of Formula Ic (Formula 1 wherein J is Q 2 , X is CR 2 , Y is N, Z is CR 4 and R 4 is H) wherein R 2 is halogen, which can then be treated with a second equivalent of the same or different halogenating reagent to provide a compound of Formula Ia wherein R 2 and R 4 are halogen.
  • Step C of Examples 1 and 34 see Step C of Examples 1 and 34.
  • compounds of Formula Ia wherein R 4 is halogen, alkyl, alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like can be prepared from compounds of Formula Ic by metallation with a reagent such as n-butyllithium (n-BuLi), lithium diisopropylamide (LDA) or sodium hydride (NaH) in a solvent such as tetrahydrofuran, dioxane or toluene at temperatures ranging from about 0 0 C to room temperature.
  • a solvent such as tetrahydrofuran, dioxane or toluene at temperatures ranging from about 0 0 C to room temperature.
  • the anion is then contacted with an electrophile resulting in the introduction of an R 4 group onto Formula Ic, thus providing a compound of Formula Ia.
  • electrophile e.g., halogenating agent or R -Lg
  • Synthesis of compounds of Formula Ib can be achieved as outlined in Scheme 3.
  • a compound of Formula 3 is JV-arylated with halides of formula Q 2 X 1 wherein X 1 is I, Cl, Br or F.
  • X 1 is I, Cl, Br or F.
  • a suitable copper source e.g., copper(I) iodide or copper(I) triflate
  • a metal carbonate base e.g., potassium or cesium carbonate
  • a suitable solvent such as xylenes, dioxane or acetonitrile
  • compounds of Formula 4 can be converted directly to Formula Ib by reaction with a halide of formula Q 1 X 1 in the presence of palladium(II) acetate and a triarylphosphine ligand and cesium fluoride in a solvent such as dioxane, tetrahydrofuran or acetonitrile at the reflux temperature of the solvent.
  • a solvent such as dioxane, tetrahydrofuran or acetonitrile
  • lithiation of a compound of Formula 4 with n-butyllithium (n-BuLi) or lithium diisopropylamide (LDA), followed by treatment of the anion with trialkylorganostannyl chlorides or boronic acids (or esters) provides compounds of Formula 5.
  • Treatment of compounds Formula 5 with a halide of formula Q 1 X 1 using well-known transition metal-catalyzed cross coupling reaction conditions provides Formula Ib compounds. Typically the reaction is run in the present of a palladium catalyst.
  • L is (alkyl) 3 Sn or B(OH) 2
  • n-butyl lithium n-BuLi
  • LDA lithium diisopropylamide
  • NaH sodium hydride
  • the anion is then contacted with an electrophile resulting in the introduction of an R 4 group onto Formula 6, thus providing a compound of Formula Ib.
  • the electrophile can be a halogen derivative such as JV-chlorosuccinimide (NCS),
  • NBS ⁇ /-bromosuccinimide
  • NIS TV-iodosuccinimide
  • hexachloroethane or
  • the electrophile can be an alkylating agent of the formula R 4 -Lg (wherein Lg is a leaving group such as Cl, Br, I or a sulfonate, for example, /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate) where R 4 is alkyl, alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like.
  • the terms "alkylation” and “alkylating agent” are not limited to R 4 being an alkyl group.
  • Example 4 illustrates the method of Scheme 4 using LDA and iodomethane.
  • compounds of Formula Ib can be prepared by reacting JV-chloroamidines of Formula 7 with enamines of Formula 8.
  • cyclization proceeds through the intermediacy of an in szYw-generated 4-morpholino-4,5- dihydroimidazole which undergoes elimination of the morpholino group to provide the compounds of Formula Ib.
  • the reaction is run in the presence of a base such as pyridine, 4-(dimethylamino)pyridine or a trialkylamine and in a suitable solvent, such as dichloromethane, trichloromethane, carbon tetrachloride or toluene, at temperatures ranging from about 0 0 C to the reflux temperature of the solvent.
  • imidazole rings of Formula Ib can also be prepared by numerous other methods described in the chemistry literature.
  • the general method described by Wiglenda et al., Journal of Medicinal Chemistry 2007, 50(1), 1475-1484 can be used to prepare compounds of Formula Ib; the method can also be readily adapted to prepare Formula Ib compounds wherein each Q 1 and/or Q 2 is an optionally substituted benzyl group.
  • Compounds of Formula 7 can be easily synthesized from amidines and JV-chlorosuccinimide according to the procedure given by Pocar et al., Tetrahedron Letters 1976, 21, 1839-1842.
  • Enamines of Formula 8 can be prepared by known methods; for example, see van der Gen et al., Tetrahedron Letters 1979, 26, 2433-2436.
  • compounds of Formula Ic can be prepared by reacting an imine of Formula 9 with a substituted /?-toluenesulfonylmethyl isocyanide of Formula 10 or a substituted benzotriazol-1-ylmethyl isocyanide of Formula 11 in the presence of a suitable base such as potassium carbonate, potassium tert-butoxide, sodium hydroxide, sodium hydride, te/t-butylamine or l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in an appropriate solvent such as methanol, dioxane, tetrahydrofuran, dimethylsulfoxide,
  • a suitable base such as potassium carbonate, potassium tert-butoxide, sodium hydroxide, sodium hydride, te/t-butylamine or l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in an appropriate solvent such as methanol, dioxane,
  • Imines of Formula 9 can be readily prepared by contacting an amine of Formula Q 2 NH 2 with an aldehyde of formula Q 1 CHO under dehydrative conditions such as heating in toluene or xylenes with use of a Dean-Stark trap to remove water formed in the reaction.
  • an acid catalyst such as /?-toluenesulfonic acid can be added to the reaction mixture to promote elimination of water.
  • Step A of Examples 1, 3, 9, 34 and 37 illustrate the preparation of a compound of Formula 9.
  • Compounds of Formula 10 can be prepared from the unsubstituted
  • the substituted benzotriazol-1-ylmethyl isocyanides of Formula 11 can be prepared by contacting benzotriazol-1-yl-methyl isocyanide with a compound of formula R 2 X 1 (wherein X 1 is halogen) in the presence of a base such as potassium carbonate, sodium hydride or potassium tert-butoxide.
  • a base such as potassium carbonate, sodium hydride or potassium tert-butoxide.
  • a base such as potassium carbonate, sodium hydride or potassium tert-butoxide.
  • Halogenation at the 2-position of the imidazole ring of Formula Ic can be achieved using methods analogous to those already described for Scheme 2 to provide compounds of Formula Ia wherein R 2 is halogen. Examples 12, 15, 30, 35 and 38 illustrate this halogenation method.
  • Aminonitriles of Formula 12 are readily available from amines of formula Q 2 NH 2 , aldehydes of formula Q 1 CHO and a cyanide source by means of the Strecker reaction.
  • a variety of solvents and cyanide sources can be employed.
  • the presence of a Lewis acid such as indium(III) chloride can be advantageous.
  • a Lewis acid such as indium(III) chloride.
  • Methanaminium salts of Formula 13 are commercially available, for example, chloromethylenedimethyliminium chloride (i.e. R 2 and X 1 are Cl) can be obtained from commercial sources. Compounds of Formula 13 can also be synthesized by methods documented in the chemistry literature.
  • the 2-imidazolecarboxaldehyde of Formula Ia 1 can be reduced with sodium borohydride in methanol to provide the corresponding compound of Formula Ia 2 (i.e. Formula Ia wherein R 4 is 2-hydroxymethyl).
  • R 4 is 2-hydroxymethyl
  • Example 21 Treatment of the 2-hydroxymethyl compound of Formula Ia 2 with diethylaminosulfur trifluoride (DAST) results in the 2-fluoromethyl derivative of Formula Ia 3 (i.e. Formula Ia wherein R 4 is -CH 2 F).
  • DAST diethylaminosulfur trifluoride
  • 2-halomethyl analogs of Formula Ia 3 can be prepared using methods described in the chemistry literature.
  • 2-bromomethyl analogs of Formula Ia 3 can be prepared by treating 2-hydroxymethyl compounds of Formula Ia 2 with hydrobromic acid in a solvent such as glacial acetic acid using the method described by Beukers et al., Journal of Medicinal Chemistry 2004, 47(15), 3707-3709.
  • the 2-imidazolecarboxaldehyde can be treated with hydroxylamine hydrochloride to provide the oxime of Formula Ia 4 (i.e. Formula Ia wherein R 4 is oxime functionality).
  • R 4 is oxime functionality
  • compounds of Formula Id can be prepared as outlined in Scheme 11.
  • compounds of Formula 15 are first halogenated analogous to the method described in Scheme 2 to provide the compounds of Formula 16, which can then be coupled with a boronic acid of formula Q 3 B(OH) 2 using well-known Suzuki palladium-catalyzed cross coupling reaction conditions.
  • Many catalysts are useful for the Suzuki reaction; particularly useful catalysts include tetrakis(triphenylphosphine)palladium(0) and [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II).
  • Solvents such as tetrahydrofuran, acetonitrile, diethyl ether and dioxane are suitable.
  • compounds of Formula Id can be prepared by introduction of the R 1 substituent via alkylation of the pyrazole ring with an alkylating agent R i -Lg wherein Lg is a leaving group such as Cl, Br, I or a sulfonate such as /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate.
  • R i -Lg wherein Lg is a leaving group such as Cl, Br, I or a sulfonate such as /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate.
  • alkylation and “alkylating agent” are not limited to R 1 being an alkyl group and include in addition to alkyl such groups as alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like.
  • Alkylation of pyrazoles using potassium carbonate in N,N-dimethylformamide or acetone are described by Kitazaki et al, Chem. Pharm. Bull. 2000, 48(12), 1935-1946 and Jeon et al., Journal of Fluorine Chemistry 2007, 128, 1191-1197.
  • reaction can be run in a variety of solvents, but typically optimal yields are obtained when the reaction is run in ethanol at a temperature between about room temperature and the reflux temperature of the solvent.
  • General procedures for this type of reaction are well documented in the chemical literature; for example, see Maya et al, Bioorganic & Medicinal Chemistry 2005, 13(6), 297-2107; and Domagala et al., Journal of Heterocyclic Chemistry 1989, 26, 1147-1158.
  • the method of Scheme 13 is also illustrated in Step C of Example 39.
  • alkylhydrazines i.e. R 1 NFINF ⁇
  • R 1 is other than hydrogen
  • these reactions result in mixtures of 1- and 2-substituted pyrazole regioisomers which can be separated using chromatography.
  • Compounds of Formula 18 can be prepared from ketones of Formula 19 and ⁇ /, ⁇ /-dimethylformamide dimethyl acetal using the method described by Maya et al., Bioorganic & Medicinal Chemistry 2005, 13(6), 297-2107. The reaction is typically conducted in a solvent such as benzene, toluene or xylenes at a temperature between about room temperature and the reflux temperature of the solvent. The method of Scheme 14 is illustrated in Step B of Example 39.
  • Ketones of Formula 19 can be prepared by reaction of acid chlorides of Formula 20 with the desired aromatic species of formula Q 1 -H under Friedel-Crafts condensation reaction conditions. Friedel-Crafts reactions are documented in a variety of published references including Lutjens et al., Journal of Medicinal Chemistry 2003, 46(10), 1870- 1877; PCT Patent Publication WO 2005/037758; and J. March, Advanced Organic Chemistry, McGraw-Hill, New York, p 490 and references cited within. The method of Scheme 15 is also illustrated in Step A of Example 39.
  • amines of Formula 24 can be converted to diazonium salts and then reacted with a copper salt (e.g., copper(I) halide, copper(II) halide or copper(I) cyanide) in the presence of an acid to provide compounds of Formula Id.
  • a copper salt e.g., copper(I) halide, copper(II) halide or copper(I) cyanide
  • the diazonium salt formed from the amine of Formula 24 is generated under standard conditions, for example, strong acid (e.g., hydrochloric acid or hydrobromic acid)
  • the cyclization reaction proceeds through the intermediacy of an in szYw-generated 4-metallotriazole which when treated with an electrophile of formula R 2 -Lg (wherein Lg is a leaving group such as Cl, Br, I or a sulfonate, for example, /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate) provides the corresponding compound of Formula Ie.
  • the reaction is run in an aprotic solvent, such as tetrahydrofuran, at temperature between about 0 0 C to the reflux temperature of the solvent.
  • an aprotic solvent such as tetrahydrofuran
  • R is a wherein M is MgX or Li lower alkyl group
  • compounds of Formula 1 and the intermediates described above can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation and reduction reactions to add or modify substituents for formation of further compounds of Formula 1.
  • Compounds wherein R 2 , R 3 , R 4 , R 5a , R 5 ⁇ or R 5c is halogen (preferably bromide or iodide) are particularly useful intermediates for transition metal-catalyzed cross-coupling reactions to prepare compounds of Formula 1.
  • R 5 ⁇ and R 5c substituents attached to the rings and ring systems of Q 1 , Q 2 and Q 3 may be more conveniently incorporated after forming the central azole ring with the rings or ring systems of Q 1 , Q 2 and Q 3 attached.
  • R 5a , R 5 ⁇ and/or R 5c is halogen or another suitable leaving group
  • the leaving group can be replaced using various electrophilic, nucleophilic and organometallic reactions known in the art to introduce other functional groups as R 5a , R 5 * 5 and R 5c .
  • Example 29 demonstrates the preparation of a compound of Formula Ia wherein R 5a is cyano (-CN) starting from the corresponding compound of Formula Ia wherein R 5a is bromo.
  • Example 43 illustrates the preparation of a compound of Formula Ia wherein R 5 ⁇ is thiocyanate (-SCN) starting from the corresponding compound of Formula Ia wherein R 5 ⁇ is iodo.
  • compounds of Formula 1 wherein a ring or ring system of Q 1 , Q 2 or Q 3 is substituted with an R 5a , R 5 ⁇ or R 5c substituent which is -U-V-T (as defined in the Summary of the Invention) can be prepared from the corresponding compounds of Formula 1 wherein R 5a , R 5 ⁇ or R 5c is a halogen or other suitable leaving group, such as by the general method described in PCT Patent Publication WO 2007/149448 (see Scheme 15 therein).
  • the solvent system was solvent A: water with 0.05% trifluoroacetic acid by volume/volume, and solvent B: acetonitrile with 0.05% trifluoroacetic acid by volume/volume (gradient started at 0 minutes with 90% solvent A and 10% solvent B and increased solvent B to 90% over 20 minutes, flow rate was 1 mL/minute). Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated.
  • the mass spectra value given in the following Examples is the molecular weight of the highest isotopic abundance parent ion (M+ 1) formed by addition of H + (molecular weight of 1) to the molecule, observed by mass spectrometry using electrospray ionization (ESI).
  • ESI electrospray ionization
  • reaction mixture was stirred at -50 0 C for 1.5 h, and then a solution of iodomethane (1.47 g, 10.3 mmol) in tetrahydrofuran (16 mL) was added.
  • the reaction mixture was slowly warmed to room temperature, stirred for 4 h, and then concentrated under reduced pressure.
  • the resulting residue was diluted with dichloromethane (50 mL), washed with water (20 mL) and saturated aqueous sodium chloride solution (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • the reaction mixture was diluted with ethyl acetate (40 mL), washed with water (20 mL) and saturated aqueous sodium chloride solution (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • the resulting material was purified by silica gel chromatography using methanol-dichloromethane (1 : 9) as eluant to provide the title compound, a compound of the present invention, as an off- white solid (0.20 g, 95.3 area % purity by ⁇ PLC) melting at 132-134 0 C.
  • Example 9 the product of Example 9) (0.280 g, 0.78 mmol) and hexachloroethane (1.10 g, 4.7 mmol) in tetrahydrofuran (5 mL) at -78 0 C was added lithium diisopropylamide (1.0 M in tetrahydrofuran, 0.390 mL, 0.78 mmol).
  • Step B Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3- fluorophenyl)- lH-imidazole
  • 2,6- ⁇ -[(3-fluorophenyl)amino)]-4-methoxybenzeneacetonitrile i.e. the product of Step A
  • dichloromethane 20 mL
  • ⁇ /-(chloromethylene)- ⁇ /-methylmethanaminium chloride (1.60 g, 12.5 mmol).
  • reaction mixture was diluted with saturated aqueous sodium carbonate solution, and the resulting aqueous mixture was extracted with dichloromethane.
  • Step A Preparation of 2,6- ⁇ -[(4-fluorophenyl)amino)]-3-methoxybenzeneacetonitrile
  • a mixture of 4-fluoroaniline (1.17 g, 10.6 mmol), 2,6-difluoro-3- methoxybenzaldehyde (2.0Og, 11.6 mmol), potassium cyanide (2.80 g, 42.4 mmol) and indium chloride (2.30 g, 10.4 mmol) in tetrahydrofuran (50 mL) was stirred at room temperature overnight.
  • the reaction mixture was diluted with water (about 100 mL) and extracted with ethyl acetate.
  • Step B Preparation of 4-bromo-5-(2,6-difluoro-3-methoxyphenyl)-l-(4- fluorophenyl)- lH-imidazole
  • N-bromosuccinimide (0.250 g, 1.40 mmol) was added to the reaction mixture and the mixture was again heated at 60 0 C overnight, after which time more N-bromosuccinimide (0.250 g, 1.40 mmol) was added and the mixture was again heated at 60 0 C overnight.
  • the reaction mixture was diluted with saturated aqueous sodium carbonate solution, and the aqueous mixture was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure.
  • Ethynyltrimethyl silane (0.216 g, 2.2 mmol) was added to the reaction mixture, stirring was continued for 2 h, and then the mixture was heated at reflux overnight. More dichlorobis(triphenylphosphine)palladium (0.147 g, 0.21 mmol) and ethynyltrimethylsilane (0.216 g, 2.2 mmol) were added to the reaction mixture, and the mixture was heated at reflux for 4 h.
  • the reaction mixture was diluted with saturated aqueous sodium carbonate solution and extracted with ethyl acetate, and the combined organic layers were washed with saturated aqueous ethylenediaminetetraacetic acid, dried over magnesium sulfate, filtered and concentrated under reduced pressure.
  • the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.244 g).
  • Step B Preparation of 4-chloro-5-(2,6-difluorophenyl)-2-ethynyl-l-(3-fluorophenyl)- lH-imidazole
  • 2-bromo-4-chloro-5-(2,6-difluorophenyl)-l-(3-fluorophenyl)-lH- imidazole i.e. the product of Step A
  • a solution of sodium hydroxide and methanol 1%, w/w, 2 mL
  • ⁇ /, ⁇ /-dimethylformamide (0.47 mL, 6.0 mmol) was added. After an additional 1 h of stirring at 0 0 C, the reaction mixture was allowed to warm to room temperature. After 1 h, the reaction mixture was diluted with aqueous citric acid solution (20%, 30 mL) and extracted with diethyl ether (100 mL). The organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by flash column chromatography on silica gel (0 to 20% gradient of ethyl acetate in n-butyl chloride as eluant) to provide the title compound, a compound of the present invention, as a pale- yellow solid (0.397 g).
  • the reaction mixture was diluted with ethyl acetate and washed with water (2x), and the ethyl acetate mixture was neutralized by the addition of saturated aqueous sodium bicarbonate solution.
  • the aqueous mixture was extracted with ethyl acetate (2x), and the combined organic layers were washed with saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure.
  • the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.470 g).
  • 1H NMR (CDCl 3 ) ⁇ 7.32 (m, 3H), 7.15 (m, 2H), 6.86 (dd, 2H), 3.70 (s, 2H), 3.66 (s, 3H).
  • the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.037 g).
  • the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.063 g).
  • reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.088 g).
  • reaction mixture was allowed to warm to room temperature, and stirred overnight. More tribromoborane (1 M in dichloromethane, 1.4 mL, 1.40 mmol) was added to the reaction mixture at room temperature, and stirring was continued for 4 h. Hydrochloric acid (1 N, 8.0 mL) was added to the reaction mixture, and then the aqueous mixture was brought to a basic pH by the addition of saturated aqueous sodium carbonate solution. The aqueous mixture was extracted with ethyl acetate, and the extract was dried over magnesium sulfate, filtered and concentrated under reduced pressure.
  • Step A Preparation of phenylmethyl ⁇ /-[3-[4-[4-chloro-2-methyl-l-(4-methylphenyl)- lH-imidazol-5-yl]-3,5-difluorophenoxy]propyl]- ⁇ /-methylcarbamate A mixture of 4-[4-chloro-2-methyl-l-(4-methylphenyl)-lH-imidazol-5-yl]-3,5- difluorophenol (i.e.
  • Example 32 the product of Example 32 (0.200 g, 0.598 mmol) and 4 A molecular sieves (1.55 g) in N, ⁇ /-dimethylformamide (3 mL) was stirred at room temperature for 3 h, and then a solution of phenylmethyl ⁇ /-(3-chloropropyl)- ⁇ /-methylcarbamate (prepared by the method described in PCT Publication WO 2007/149448) (0.434 g, 1.80 mmol) and tetrabutylammonium iodide (0.044 g, 0.120 mmol) in ⁇ /, ⁇ /-dimethylformamide (1 mL) was added.
  • phenylmethyl ⁇ /-(3-chloropropyl)- ⁇ /-methylcarbamate prepared by the method described in PCT Publication WO 2007/149448
  • tetrabutylammonium iodide 0.044 g, 0.120 mmol
  • Step B Preparation of 3-[4-[4-chloro-2-methyl- 1 -(4-methylphenyl)- lH-imidazol-5- yl]-3 ,5 -difluorophenoxy] -//-methyl- 1 -propanamide hydrochloride
  • Step A Preparation of N-[(2,6-difluoro-4-methoxyphenyl)methylene]-6- (trifluoromethyl)-3 -pyridinamine
  • Step C Preparation of 5-[4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 - yl]-2-(trifluoromethyl)pyridine A mixture of 5-[5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-l-yl]-2-
  • Step A Preparation of ⁇ /-[(6-chloro-3-pyridinyl)methylene]-2,6-difluoro-4- methoxybenzenamine
  • Step A Preparation of l-(4-chlorophenyl)-2-(2,6-difluorophenyl)ethanone A mixture of 2,6-difluorophenylacetic acid (5.63 g, 31.1 mmol) and thionyl chloride
  • Step B) the product of Step B) (0.22 g, 0.66 mmol), 3-fiuorophenylboronic acid (0.18 g, 1.32 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.02 g, 0.02 mmol), 2- dicyclohexylphosphino-2',6'-dimethoxybiphenyl (0.04 g, 0.09 mmol), and potassium phosphate (0.43 g, 2.0 mmol), and the mixture was then heated at 100 0 C overnight. The reaction mixture was allowed to cool to room temperature, and then concentrated under reduced pressure.
  • the resulting material was purified by medium pressure liquid chromatography on silica gel (5:95 to 30:70 gradient of ethyl acetate in hexanes as eluant) to provide a solid.
  • the solid was triturated with n-butyl chloride, filtered and air-dried to provide the title compound, a compound of the present invention, as an off-white solid (0.08 g)- 1 H NMR (CDCl 3 ): ⁇ 7.45-7.38 (m, IH), 7.28-7.20 (m, 2H), 7.04-6.79 (m, 4H), 3.71 (s, 3H),
  • the reaction mixture was diluted with water (50 mL) and extracted with hexanes (50 mL). The aqueous layer was then acidified to pH 4 with aqueous hydrochloric acid (3 N) solution and extracted with diethyl ether (3 x 100 mL). The combined diethyl ether layers were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a tan solid (4.6 g).
  • Step B Preparation of 5-bromo-4-(2-chloro-4-fluorophenyl)- 1 ,3-dimethyl- IH- pyrazole
  • 4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine i.e. the product of Step A
  • acetonitrile 50 mL
  • copper(II) bromide 3.94 g, 17.7 mmol
  • reaction mixture was cooled to about 0 0 C with an ice-water bath, and then tert-butyi nitrite (90% technical grade, 2.33 mL, 17.7 mmol) was added dropwise over 5 minutes.
  • the reaction mixture was allowed to warm slowly to room temperature.
  • Aqueous hydrochloric acid solution (1 N, 20 mL) and ethyl acetate (20 mL) were added to the reaction mixture, and then the mixture was filtered through a pad (2 cm) of Celite® (diatomaceous filter aid).
  • the Celite® pad was washed with ethyl acetate (20 mL), the layers were separated, and the organic layer was washed with aqueous hydrochloric acid (1 N) solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to provide the title compound as an orange-brown semisolid.
  • the reaction mixture was heated at reflux for 3 h and then cooled to room temperature and aqueous hydrochloric acid solution (1 N, 3 rnL) was added.
  • the aqueous mixture was extracted with ethyl acetate (20 mL), and the organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to provide an oily material.
  • the oily material was purified by silica gel (5 g) column chromatography (3 to 100% ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a yellow oil (118 mg).
  • Step B Preparation of 4-chloro-l-(4-chlorophenyl)-5-(2,4-difluorophenyl)-lH-l,2,3- triazole
  • ethylmagnesium chloride 2 M in tetrahydrofuran, 1.2 mL, 2.39 mmol
  • l-ethynyl-2,4-difluorobenzene 0.300 g, 2.17 mmol
  • the reaction mixture was heated at 50 0 C for 15 minutes and then allowed to cool to room temperature.
  • a solution of l-azido-4-chlorobenzene i.e.
  • Step A) the product of Step A) (0.328 g, 2.39 mmol) in tetrahydrofuran (1 mL) was added to the reaction mixture, followed by heating at 50 0 C. After 1 h, hexachloroethane (1.03 g, 4.34 mmol) was added to the reaction mixture. After 2 h, the reaction mixture was allowed to cool to room temperature, and hydrochloric acid (2 M in diethyl ether, 2 mL) was added.
  • Q 2 is 4-Cl-Ph, R 2 is Cl and R 4 is Me.
  • Q 2 is 4-Cl-Ph, R 2 is Cl and R 4 is Me.
  • the present disclosure also includes Tables IA through 934A, each of which is constructed the same as Table 1 above except that the row heading in Table 1 (i.e. "Q 2 is 4-Cl-Ph, R 2 is Cl and R 4 is Me") is replaced with the respective row heading shown below.
  • Table IA the row heading is "Q 2 is 4-Cl-Ph, R 2 is Br and R 4 is Me", and (R 5a ) m is as defined in Table 1 above.
  • the first entry in Table IA specifically discloses 4-bromo-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole.
  • Tables 2A through 934A are constructed similarly.
  • IA Q 2 is 4-Cl-Ph, R 2 is Br and R 4 is Me.
  • Q 2 is 4-Cl-Ph, R 2 is Cl and R 4 is CFH 2 .
  • Q 2 is 4-Cl-Ph, R 2 is I and R 4 is Me.
  • Q 2 is 4-Cl-Ph, R 2 is Me and R 4 is Me.
  • Q 2 is 4-Cl-Ph, R 2 is Me and R 4 is Cl.
  • Q 2 is 4-Cl-Ph, R 2 is Me and R 4 is Br.
  • Q 2 is 4-Cl-Ph, R 2 is Me and R 4 is I.
  • Q 2 is 4-Cl-Ph, R 2 is Me and R 4 is MeO.
  • Q 2 is 4-Cl-Ph, R 2 is MeO and R 4 is Me.
  • HA Q 2 is 4-Cl-Ph, R 2 is Br and R 4 is Cl.
  • Q 2 is 4-Cl-Ph, R 2 is Cl and R 4 is Br.
  • Q 2 is 4-Cl-Ph, R 2 is Cl and R 4 is Cl.
  • Q 2 is 4-Cl-Ph, R 2 is Me and R 4 is MeS.
  • Q 2 is 4-Cl-Ph, R 2 is MeS and R 4 is Me.
  • Q 2 is 4-Cl-Ph, R 2 is Et and R 4 is Br.
  • Q 2 is 4-Cl-Ph, R 2 is Me and R 4 is Et.
  • Q 2 is 4-Cl-Ph, R 2 is Me and R 4 is CN.
  • Q 2 is 4-Cl-Ph, R 2 is Me and R 4 is H.
  • Q 2 is 4-Cl-Ph, R 2 is Cl and R 4 is H.
  • Q 2 is 4-Cl-Ph, R 2 is Br and R 4 is H.
  • Q 2 is 3 -Cl-Ph, R 2 is Cl and R 4 is Me.
  • Q 2 is 3 -Cl-Ph, R 2 is Br and R 4 is Me.
  • Q 2 is 3 -Cl-Ph, R 2 is Me and R 4 is Me.
  • Q 2 is 3 -Cl-Ph, R 2 is Br and R 4 is Br.
  • Q 2 is 3 -Cl-Ph, R 2 is Br and R 4 is Cl.
  • Q 2 is 3 -Cl-Ph, R 2 is Cl and R 4 is Cl.
  • Q 2 is 4-F-Ph, R 2 is Cl and R 4 is CFH 2 .
  • Q 2 is 4-F-Ph, R 2 is Br and R 4 is Me.
  • Q 2 is 4-F-Ph, R 2 is I and R 4 is Me.
  • Q 2 is 4-F-Ph, R 2 is Me and R 4 is Me.
  • Q 2 is 4-F-Ph, R 2 is Me and R 4 is Cl.
  • Q 2 is 4-F-Ph, R 2 is Me and R 4 is Br.
  • Q 2 is 4-F-Ph, R 2 is Me and R 4 is I.
  • Q 2 is 4-F-Ph, R 2 is Br and R 4 is Br.
  • Q 2 is 4-F-Ph, R 2 is Br and R 4 is Cl.
  • Q 2 is 4-F-Ph, R 2 is Me and R 4 is H.
  • Q 2 is 4-F-Ph, R 2 is Cl and R 4 is H.
  • Q 2 is 4-F-Ph, R 2 is Br and R 4 is H.
  • Q 2 is 3-F-Ph, R 2 is Cl and R 4 is CFH 2 .
  • 57A Q 2 is 3-F-Ph, R 2 is Br and R 4 is Me.
  • 58A Q 2 is 3-F-Ph, R 2 is I and R 4 is Me.
  • 59A Q 2 is 3-F-Ph, R 2 is Me and R 4 is Me.
  • 61A Q 2 is 3-F-Ph, R 2 is Me and R 4 is Br.
  • Q 2 is 3-F-Ph, R 2 is Br and R 4 is Cl.
  • 67A Q 2 is 3-F-Ph, R 2 is Me and R 4 is H.
  • 74A Q 2 is 3-CF 2 HO-Ph, R 2 is Me and R 4 is Me.
  • Q 2 is 3-CF 2 HO-Ph, R 2 is Me and R 4 is Cl.
  • 76A Q 2 is 3-CF 2 HO-Ph, R 2 is Me and R 4 is Br.
  • 77A Q 2 is 3-CF 2 HO-Ph, R 2 is Me and R 4 is I.
  • 81A Q 2 is 3-CF 2 HO-Ph, R 2 is Cl and R 4 is Cl.
  • 82A Q 2 is 3-CF 2 HO-Ph, R 2 is Me and R 4 is H.
  • Q 2 is 4-Me-Ph, R 2 is Cl and R 4 is Me.
  • Q 2 is 4-Me-Ph, R 2 is Cl and R 4 is CFH 2 .
  • 87A Q 2 is 4-Me-Ph, R 2 is Br and R 4 is Me.
  • 89A Q 2 is 4-Me-Ph, R 2 is Me and R 4 is Me.
  • 91A Q 2 is 4-Me-Ph, R 2 is Me and R 4 is Br.
  • 92A Q 2 is 4-Me-Ph, R 2 is Me and R 4 is I.
  • Q 2 is 4-Me-Ph, R 2 is Cl and R 4 is Br.
  • 96A Q 2 is 4-Me-Ph, R 2 is Cl and R 4 is Cl.
  • 97A Q 2 is 4-Me-Ph, R 2 is Me and R 4 is H.
  • 98A Q 2 is 4-Me-Ph, R 2 is Cl and R 4 is H.
  • Q 2 is 4-Me-Ph, R 2 is Br and R 4 is H.
  • IOOA Q 2 is 3-Me-Ph, R 2 is Cl and R 4 is Me. Table Row Heading
  • Q 2 is 3-Me-Ph, R 2 is Cl and R 4 is CFH 2 .
  • 106A Q 2 is 3-Me-Ph, R 2 is Me and R 4 is Br.
  • 107A Q 2 is 3-Me-Ph, R 2 is Me and R 4 is I.
  • 109A Q 2 is 3-Me-Ph, R 2 is Br and R 4 is Cl.
  • HOA Q 2 is 3-Me-Ph, R 2 is Cl and R 4 is Br.
  • H iA Q 2 is 3-Me-Ph, R 2 is Cl and R 4 is Cl.
  • Q 2 is 3-Me-Ph, R 2 is Me and R 4 is H.
  • 113A Q 2 is 3-Me-Ph, R 2 is Cl and R 4 is H.
  • 114A Q 2 is 3-Me-Ph, R 2 is Br and R 4 is H.
  • 116A Q 2 is 4-Et-Ph, R 2 is Cl and R 4 is CFH 2 .
  • 117A Q 2 is 4-Et-Ph, R 2 is Br and R 4 is Me.
  • 118A Q 2 is 4-Et-Ph, R 2 is I and R 4 is Me.
  • Q 2 is 4-Et-Ph, R 2 is Me and R 4 is Me.
  • Q 2 is 4-Et-Ph, R 2 is Me and R 4 is Cl.
  • 121A Q 2 is 4-Et-Ph, R 2 is Me and R 4 is Br.
  • Q 2 is 4-Et-Ph, R 2 is Me and R 4 is I.
  • 123A Q 2 is 4-Et-Ph, R 2 is Br and R 4 is Br.
  • 124A Q 2 is 4-Et-Ph, R 2 is Br and R 4 is Cl.
  • 125A Q 2 is 4-Et-Ph, R 2 is Cl and R 4 is Br.
  • 127A Q 2 is 4-Et-Ph, R 2 is Me and R 4 is H.
  • Q 2 is 4-Et-Ph, R 2 is Cl and R 4 is H.
  • Q 2 is 4-Et-Ph, R 2 is Br and R 4 is H.
  • 131A Q 2 is 4-Cl, 3-F-Ph, R 2 is Cl and R 4 is CFH 2 .
  • 132A Q 2 is 4-Cl, 3-F-Ph, R 2 is Br and R 4 is Me.
  • 133A Q 2 is 4-Cl, 3-F-Ph, R 2 is I and R 4 is Me.
  • 134A Q 2 is 4-Cl, 3-F-Ph, R 2 is Me and R 4 is Me.
  • Q 2 is 4-Cl, 3-F-Ph, R 2 is Me and R 4 is Cl.
  • 136A Q 2 is 4-Cl, 3-F-Ph, R 2 is Me and R 4 is Br.
  • 138A Q 2 is 4-Cl, 3-F-Ph, R 2 is Br and R 4 is Br.
  • Q 2 is 4-Cl, 3-F-Ph, R 2 is Cl and R 4 is Br.
  • Q 2 is 4-Cl, 3-F-Ph, R 2 is Me and R 4 is H.
  • 143A Q 2 is 4-Cl, 3-F-Ph R 2 is Cl and R 4 is H.
  • 144A Q 2 is 4-Cl, 3-F-Ph, R 2 is Br and R 4 is H.
  • 146A Q 2 is 2-Cl, 4-F-Ph, R 2 is Cl and R 4 is CFH 2 .
  • Q 2 is 2-Cl, 4-F-Ph, R 2 is Br and R 4 is Me.
  • a Q 2 is 2-Cl, 4-F-Ph, R 2 is Me and R 4 is Me.
  • Q 2 is 2-Cl, 4-F-Ph, R 2 is Me and R 4 is Cl.
  • 151A Q 2 is 2-Cl, 4-F-Ph, R 2 is Me and R 4 is Br.
  • 152A Q 2 is 2-Cl, 4-F-Ph, R 2 is Me and R 4 is I.
  • 154A Q 2 is 2-Cl, 4-F-Ph, R 2 is Br and R 4 is Cl.
  • 155A Q 2 is 2-Cl, 4-F-Ph, R 2 is Cl and R 4 is Br.
  • 156A Q 2 is 2-Cl, 4-F-Ph, R 2 is Cl and R 4 is Cl.
  • 157A Q 2 is 2-Cl, 4-F-Ph, R 2 is Me and R 4 is H.
  • 158A Q 2 is 2-Cl, 4-F-Ph R 2 is Cl and R 4 is H.
  • 159A Q 2 is 2-Cl, 4-F-Ph, R 2 is Br and R 4 is H.
  • Q 2 is 4-F, 3-Me-Ph, R 2 is Cl and R 4 is Me.
  • Q 2 is 4-F, 3-Me-Ph, R 2 is Cl and R 4 is CFH 2 .
  • Q 2 is 4-F, 3-Me-Ph, R 2 is Br and R 4 is Me.
  • Q 2 is 4-F, 3-Me-Ph, R 2 is I and R 4 is Me.
  • 164A Q 2 is 4-F, 3-Me-Ph, R 2 is Me and R 4 is Me.
  • Q 2 is 4-F, 3-Me-Ph, R 2 is Me and R 4 is Cl.
  • 166A Q 2 is 4-F, 3-Me-Ph, R 2 is Me and R 4 is Br.
  • 167A Q 2 is 4-F, 3-Me-Ph, R 2 is Me and R 4 is I.
  • 168A Q 2 is 4-F, 3-Me-Ph, R 2 is Br and R 4 is Br.
  • Q 2 is 4-F, 3-Me-Ph, R 2 is Br and R 4 is Cl.
  • Q 2 is 4-F, 3-Me-Ph, R 2 is Cl and R 4 is Br.
  • Q 2 is 4-F, 3-Me-Ph, R 2 is Cl and R 4 is Cl.
  • 172A Q 2 is 4-F, 3-Me-Ph, R 2 is Me and R 4 is H.
  • Q 2 is 4-F, 3-Me-Ph, R 2 is Cl and R 4 is H.
  • 174A Q 2 is 4-F, 3-Me-Ph, R 2 is Br and R 4 is H.
  • a Q 2 is 3,4-di-F-Ph, R 2 is Cl and R 4 is Me.
  • 177A Q 2 is 3,4-di-F-Ph, R 2 is Br and R 4 is Me.
  • 179A Q 2 is 3,4-di-F-Ph, R 2 is Me and R 4 is Me.
  • Q 2 is 3,4-di-F-Ph, R 2 is Me and R 4 is Cl.
  • Q 2 is 3,4-di-F-Ph, R 2 is Me and R 4 is Br.
  • Q 2 is 3,4-di-F-Ph, R 2 is Me and R 4 is I.
  • Q 2 is 3,4-di-F-Ph, R 2 is Br and R 4 is Br.
  • 185A Q 2 is 3,4-di-F-Ph, R 2 is Cl and R 4 is Br.
  • 187A Q 2 is 3,4-di-F-Ph, R 2 is Me and R 4 is H.
  • 188A Q 2 is 3,4-di-F-Ph, R 2 is Cl and R 4 is H.
  • 190A Q 2 is 3,4-di-Cl-Ph, R 2 is Cl and R 4 is Me.
  • Q 2 is 3,4-di-Cl-Ph, R 2 is Cl and R 4 is CFH 2 .
  • a Q 2 is 3,4-di-Cl-Ph, R 2 is Br and R 4 is Me.
  • Q 2 is 3,4-di-Cl-Ph, R 2 is I and R 4 is Me.
  • Q 2 is 3,4-di-Cl-Ph, R 2 is Me and R 4 is Me.
  • 196A Q 2 is 3,4-di-Cl-Ph, R 2 is Me and R 4 is Br.
  • Q 2 is 3,4-di-Cl-Ph, R 2 is Cl and R 4 is Br.
  • 201A Q 2 is 3,4-di-Cl-Ph, R 2 is Cl and R 4 is Cl.
  • 202A Q 2 is 3,4-di-Cl-Ph, R 2 is Me and R 4 is H.
  • 204A Q 2 is 3,4-di-Cl-Ph, R 2 is Br and R 4 is H.
  • Q 2 is 3,5-di-MeO-Ph, R 2 is Cl and R 4 is CFH 2 .
  • 207A Q 2 is 3,5-di-MeO-Ph, R 2 is Br and R 4 is Me.
  • Q 2 is 3,5-di-MeO-Ph, R 2 is Me and R 4 is Me.
  • 210A Q 2 is 3,5-di-MeO-Ph, R 2 is Me and R 4 is Cl.
  • 211A Q 2 is 3,5-di-MeO-Ph, R 2 is Me and R 4 is Br. Table Row Heading
  • Q 2 is 3,5-di-MeO-Ph, R 2 is Br and R 4 is Br.
  • Q 2 is 3,5-di-MeO-Ph, R 2 is Cl and R 4 is Br.
  • 216A Q 2 is 3,5-di-MeO-Ph, R 2 is Cl and R 4 is Cl.
  • Q 2 is 3,5-di-MeO-Ph, R 2 is Mt ; and R 4 is H.
  • Q 2 is 3,5-di-MeO-Ph, R 2 is Cl and R 4 is H.
  • Q 2 is 3,5-di-MeO-Ph, R 2 is Br and R 4 is H.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Cl and R 4 is Me.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Cl and R 4 is CFH 2 .
  • 222A Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Br and R 4 is Me.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is I and R 4 is Me.
  • 224A Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Me and R 4 is Me.
  • 225A Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Me and R 4 is Cl.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Me and R 4 is Br.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Me and R 4 is I.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Br and R 4 is Br.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Br and R 4 is Cl.
  • 230A Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Cl and R 4 is Br.
  • IA Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Cl and R 4 is Cl.
  • 233A Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Cl and R 4 is H.
  • Q 2 is 2-Cl, 3,5-di-MeO-Ph, R 2 is Br and R 4 is H.
  • 235A Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Cl and R 4 is Me.
  • Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Cl and R 4 is CFH 2 .
  • Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Br and R 4 is Me.
  • Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is I and R 4 is Me.
  • Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Me and R 4 is Me.
  • 240A Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Me and R 4 is Cl.
  • Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Me and R 4 is Br.
  • Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Me and R 4 is I.
  • 243A Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Br and R 4 is Br.
  • Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Br and R 4 is Cl.
  • Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Cl and R 4 is Br.
  • Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Cl and R 4 is Cl.
  • Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Me and R 4 is H.
  • Q 2 is 4-Cl, 3,5-di-MeO-Ph, R 2 is Br and R 4 is H.
  • Q 2 is 4-Cl-Bn, R 2 is Cl and R 4 is Me.
  • Q 2 is 4-Cl-Bn, R 2 is Cl and R 4 is CFH 2 .
  • Q 2 is 4-Cl-Bn, R 2 is Br and R 4 is Me.
  • Q 2 is 4-Cl-Bn, R 2 is I and R 4 is Me.
  • Q 2 is 4-Cl-Bn, R 2 is Me and R 4 is Me.
  • 255A Q 2 is 4-Cl-Bn, R 2 is Me and R 4 is Cl.
  • 256A Q 2 is 4-Cl-Bn, R 2 is Me and R 4 is Br.
  • Q 2 is 4-Cl-Bn, R 2 is Me and R 4 is I.
  • Q 2 is 4-Cl-Bn, R 2 is Br and R 4 is Br.
  • Q 2 is 4-Cl-Bn, R 2 is Br and R 4 is Cl.
  • 260A Q 2 is 4-Cl-Bn, R 2 is Cl and R 4 is Br.
  • Q 2 is 4-Cl-Bn, R 2 is Cl and R 4 is Cl.
  • Q 2 is 4-Cl-Bn, R 2 is Me and R 4 is H.
  • Q 2 is 4-Cl-Bn, R 2 is Cl and R 4 is H.
  • 264A Q 2 is 4-Cl-Bn, R 2 is Br and R 4 is H.
  • Q 2 is 4-F-Bn, R 2 is Cl and R 4 is Me.
  • Q 2 is 4-F-Bn, R 2 is Cl and R 4 is CFH 2 .
  • Q 267A Q 2 is 4-F-Bn, R 2 is Br and R 4 is Me.
  • Q 2 is 4-F-Bn, R 2 is I and R 4 is Me.
  • Q 2 is 4-F-Bn, R 2 is Me and R 4 is Me.
  • 270A Q 2 is 4-F-Bn, R 2 is Me and R 4 is Cl.
  • Q 2 is 4-F-Bn, R 2 is Me and R 4 is Br.
  • Q 2 is 4-F-Bn, R 2 is Me and R 4 is I.
  • Q 2 is 4-F-Bn, R 2 is Br and R 4 is Br.
  • Q 2 is 4-F-Bn, R 2 is Br and R 4 is Cl.
  • 275A Q 2 is 4-F-Bn, R 2 is Cl and R 4 is Br.
  • Q 2 is 4-F-Bn, R 2 is Cl and R 4 is Cl.
  • Q 277A Q 2 is 4-F-Bn, R 2 is Me and R 4 is H.
  • Q 2 is 4-F-Bn, R 2 is Cl and R 4 is H.
  • Q 2 is 4-F-Bn, R 2 is Br and R 4 is H.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Cl and R 4 is CFH 2 .
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Br and R 4 is Me.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is I and R 4 is Me.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Me and R 4 is Me.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Me and R 4 is Cl.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Me and R 4 is Br.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Me and R 4 is I.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Me and R 4 is MeO.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is MeO and R 4 is Me.
  • 290A Q 2 is 6-Cl-3-pyridinyl, R 2 is Br and R 4 is Br.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Br and R 4 is Cl.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Cl and R 4 is Br.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Cl and R 4 is Cl.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Me and R 4 is MeS.
  • Q 2 is 6-Cl-3-pyridinyl
  • R 2 is MeS
  • R 4 is Me.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Et and R 4 is Br.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Et and R 4 is Cl.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Et and R 4 is Me.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Me and R 4 is Et.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Cl and R 4 is Et.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Me and R 4 is CN.
  • Q 2 is 6-Cl-3-pyridinyl, R 2 is Me and R 4 is H.
  • 303A Q 2 is 6-Cl-3-pyridinyl, R 2 is Cl and R 4 is H.
  • 304A Q 2 is 6-Cl-3-pyridinyl, R 2 is Br and R 4 is H.
  • Q 2 is 6-Me-3-pyridinyl, R 2 is Cl and R 4 is CFH 2 .
  • Q 2 is 6-Me-3-pyridinyl, R 2 is Br and R 4 is Me.
  • Q 2 is 6-Me-3-pyridinyl, R 2 is I and R 4 is Me.
  • a Q 2 is 6-Me-3-pyridinyl, R 2 is Me and R 4 is Me.
  • Q 2 is 6-Me-3-pyridinyl, R 2 is Me and R 4 is Br.
  • Q 2 is 6-Me-3-pyridinyl, R 2 is Me and R 4 is I.
  • Q 2 is 6-Me-3-pyridinyl, R 2 is Br and R 4 is Br.
  • Q 2 is 6-Me-3-pyridinyl, R 2 is Br and R 4 is Cl.
  • Q 2 is 6-Me-3-pyridinyl, R 2 is Cl and R 4 is Br.
  • Q 2 is 6-Me-3-pyridinyl, R 2 is Me and R 4 is H.
  • Q 2 is 6-Me-3-pyridinyl, R 2 is Cl and R 4 is H.
  • Q 2 is 6-Me-3-pyridinyl, R 2 is Br and R 4 is H.
  • 320A Q 2 is 6-MeO-3-pyridinyl, R 2 is Cl and R 4 is Me.
  • Q 2 is 6-MeO-3-pyridinyl, R 2 is Cl and R 4 is CFH 2 .
  • Q 2 is 6-MeO-3-pyridinyl, R 2 is Br and R 4 is Me.
  • Q 2 is 6-MeO-3-pyridinyl, R 2 is I and R 4 is Me.
  • Q 2 is 6-MeO-3-pyridinyl, R 2 is Me and R 4 is Me.

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Abstract

Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, INSERT FORMULA 1 HERE wherein J is Q2 or R1; X is N, CR2 or CQ3; Y is N or CR3; Z is N or CR4; and Q1, Q2, Q3, R1 R2 and R3 are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention.

Description

TITLE FUNGICIDAL SUBSTITUTED AZOLES
FIELD OF THE INVENTION
This invention relates to certain azoles, their JV-oxides, salts and compositions, and methods of their use as fungicides.
BACKGROUND OF THE INVENTION
The control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. 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 for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different sites of action.
Almansa et al., Journal of Medical Chemistry 2003, 46, 3463-3475 disclose certain 1,5-diarylimidazole derivatives and their use as cyclooxygenase-2 (COX-2) inhibitors. Suketaka et al., Bulletin of the Chemical Society of Japan 1984, 57(2), 544-547 disclose certain 3,4-diaryl-4H-l,2,4-triazoles.
SUMMARY OF THE INVENTION
This invention is directed to compounds of Formula 1 (including all geometric and stereoisomers), //-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides:
Figure imgf000002_0001
wherein
J iS Q2 Or R1; X is N, CR2 Or CQ3; Y is N or CR3;
Z is N or CR4;
Q1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5a; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=0) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or QR^R^W1; W1 is a phenyl ring optionally substituted with up to 5 substituents independently selected from R5a; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, the ring optionally substituted with up to 5 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members;
Q2 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5^; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5^ on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W2; W2 is a phenyl ring optionally substituted with up to 5 substituents independently selected from R5^; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, the ring optionally substituted with up to 5 substituents independently selected from R5^ on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl,
C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; Q3 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5c; or a 5- to
6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W3;
W3 is a phenyl ring optionally substituted with up to 5 substituents independently selected from R5c; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, the ring optionally substituted with up to 5 substituents independently selected from R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; R1 is C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C1-C7 haloalkyl, C2-C7 haloalkenyl,
C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C4-C1Q alkylcycloalkyl, C4-C1Q cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C1-C7 alkoxy, C1-C7 haloalkoxy, C2-C7 alkoxyalkyl, C1-C7 alkylthio, C1-C7 haloalkylthio, C2-C7 alkylthioalkyl, C1-C7 alkylsulfϊnyl, C1-C7 alkylsulfonyl, C1-C7 haloalkylsulfmyl, C1-C7 haloalkylsulfonyl, C1-C7 alkylamino, C2-C7 dialkylamino, C2-C7 alkylcarbonylamino or C1-C7 hydroxyalkyl; each R2, R3 and R4 is independently H, halogen, cyano, amino, nitro, -CHO, C2-C7 alkenyl, C2-C7 alkynyl, C2-C7 haloalkenyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C4-C1O alkylcycloalkyl, C4-C1Q cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C1-C7 alkoxy, C1-C7 haloalkoxy, C2-C7 alkoxyalkyl, C1-C7 alkylthio, C1-C7 haloalkylthio, C2-C7 alkylthioalkyl, C1-C7 alkylsulfmyl, C1-C7 alkylsulfonyl, C1-C7 haloalkylsulfmyl, C1-C7 haloalkylsulfonyl, C1-C7 alkylamino, C2-C7 dialkylamino, C1-C7 hydroxyalkyl, -SCN or CH=NOR11 ; or
C1-C7 alkyl or C1-C7 haloalkyl, each optionally substituted with up to 3 substituents independently selected from hydroxy, cyano, C(=O)OR8, C(=O)NR9aR9b, C(=O)R10 and CH=NOR11; each R5a, R5b and R5c is independently halogen, cyano, hydroxy, nitro, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C1-C7 haloalkyl, C2-C7 haloalkenyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C4-C1Q alkylcycloalkyl, C4-C1Q cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C3-C7 cycloalkoxy, C3-C7 halocycloalkoxy, C1-C7 alkoxy, C1-C7 haloalkoxy, C1-Cg alkylthio, C1-C7 haloalkylthio, C1-C7 alkylsulfϊnyl, C1-C7 alkylsulfonyl, C1-C7 haloalkylsulfmyl, C1-C7 haloalkylsulfonyl, C1-C7 alkylamino, C2-C7 dialkylamino, C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl, C2-C7 alkylcarbonylamino, C3-C10 trialkylsilyl, SF5, -SCN, C(=S)NH2 or -U-V-T; each U is independently O, S(=O)n, NR12 or a direct bond; each V is independently C1-Cg alkylene, C2-Cg alkenylene, C3-Cg alkynylene, C3-Cg cycloalkylene or C3-C6 cycloalkenylene, wherein up to 3 carbon atoms are independently selected from C(=O), each optionally substituted with up to 5 substituents independently selected from halogen, cyano, nitro, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy and C1-C6 haloalkoxy; each T is independently NR13aR13b, OR14 or S(=O)nR14; each R7a is independently H, cyano or C1-C4 alkyl; each R7b is independently H or C1-C4 alkyl; or a pair of R7a and R7b attached to the same carbon atom are taken together with the carbon atom to form a 3- to 6-membered saturated carbocyclic ring; each R6 is independently H, cyano, C1-C3 alkyl or C1-C3 haloalkyl; each R8, R9a, R9b? RlO and Rl 1 [s independently H, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C1-C7 haloalkyl, C2-C7 haloalkenyl, C3-C7 cycloalkyl or C3-C7 halocycloalkyl; each R12 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkylcarbonyl,
C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); each R13a and R13b is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl,
C3"C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); or a pair of R13a and R13^ attached to the same nitrogen atom are taken together with the nitrogen atom to form a 3- to 6-membered heterocyclic ring, the ring optionally substituted with up to 5 substituents independently selected from R15; each R14 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); each R15 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy; each n is independently 0, 1 or 2; and each p and f are independently 0, 1 or 2 in each instance of S(=O)p(=NR6)f, provided that the sum of p and f is 0, 1 or 2; provided that:
(a) when J is R1, then X is CQ3;
(b) when J is Q2, then X is N or CR2, and if X is N or CH, then Z is other than CH; (c) for compounds other than l-(4-chlorophenyl)-5-(4-fluorophenyl)-2-methyl-lH- imidazole or 4-chloro- 1 -(4-chlorophenyl)-5-(4-fluorophenyl)-2-methyl- IH- imidazole, when Q1 is a phenyl ring which is unsubstituted by R5a at both ortho positions, then when X is N or CR2 and Q2 is a phenyl ring, the Q2 phenyl ring is substituted by at least one R5^ at an ortho position; and when X is CQ3 and Q3 is a phenyl ring, the Q3 phenyl ring is substituted by at least one R5c at an ortho position;
(d) at least one and no more than two of X, Y and Z is nitrogen;
(e) the compound is not a compound of F-I through F-4, as shown below
Figure imgf000007_0001
F-4
(g) the compound is not 4- [2-ethyl-l-(4-methoxyphenyl)-lH-imidazol-5-yl] -pyridine, 4-[l-(4-methoxyphenyl)-2-methyl-lH-imidazol-5-yl]pyridine or 3,5-dichloro-2- (4-iodo-5-phenyl-lH-l,2,3-triazol-l-yl)pyridine; and (e) when J is Q2, X is CR2, Y is N and Z is N, then R2 is other than Η. More particularly, this invention pertains to a compound of Formula 1 (including all geometric and stereoisomers), an JV-oxide or a salt thereof.
This invention also relates to a fungicidal composition comprising a fungicidally effective amount of a compound of Formula 1 (or an JV-oxide or salt thereof) and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
This invention also relates to a fungicidal composition comprising a mixture of a compound of Formula 1 (or an JV-oxide or salt thereof) and at least one other fungicide (e.g., at least one other fungicide having a different site of action).
This invention further relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of the invention (e.g., as a composition described herein).
DETAILS OF THE INVENTION
As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having", "contains" or "containing" or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus 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, process, method, article, or apparatus. 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 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.
As referred to in the present disclosure and claims, "plant" includes members of Kingdom Plantae, particularly seed plants (Spermatopsida), at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature, reproductive stages (e.g., plants producing flowers and seeds). Portions of plants include geotropic members typically growing beneath the surface of the growing medium (e.g., soil), such as roots, tubers, bulbs and corms, and also members growing above the growing medium, such as foliage (including stems and leaves), flowers, fruits and seeds. As referred to herein, the term "seedling", used either alone or in a combination of words means a young plant developing from the embryo of a seed.
As referred to herein, the term "broadleaf ' used either alone or in words such as "broadleaf crop" means dicot or dicotyledon, a term used to describe a group of angiosperms characterized by embryos having two cotyledons. As used herein, the term "alkylating agent" refers to a chemical compound in which a carbon-containing radical is bound through a carbon atom to leaving group such as halide or sulfonate, which is displaceable by bonding of a nucleophile to said carbon atom. Unless otherwise indicated, the term "alkylating" does not limit the carbon-containing radical to alkyl; the carbon-containing radicals in alkylating agents include the variety of carbon-bound substituent radicals specified, for example, for R2, R3 and R4.
In the above recitations, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, /-propyl, or the different butyl, pentyl, hexyl or heptyl isomers. "Alkenyl" includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl, hexenyl and heptenyl isomers. "Alkenyl" also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl, hexynyl and heptynyl isomers. "Alkynyl" can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl. "Alkylene" denotes a straight-chain or branched alkanediyl. Examples of "alkylene" include CH2, CH2CH2, CH(CH3), CH2CH2CH2, CH2CH(CH3) and the different butylene, pentylene and hexylene isomers. "Alkenylene" denotes a straight-chain or branched alkenediyl containing one olefmic bond. Examples of "alkenylene" include CH=CH, CH2CH=CH, CH=C(CH3). "Alkynylene" denotes a straight-chain or branched alkynediyl containing one triple bond. Examples of "alkynylene" include CH2C≡C, C≡CCH2 and the different butynylene, pentynylene and hexynylene isomers.
"Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy, hexyloxy and heptyloxy isomers. "Alkylthio" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio, hexylthio and heptylthio isomers. "Alkylsulfmyl" includes both enantiomers of an alkylsulfinyl group. Examples of "alkylsulfϊnyl" include CH3S(=O), CH3CH2S(=O), CH3CH2CH2S(=O), (CH3)2CHS(=O) and the different butylsulfϊnyl, pentylsulfinyl, hexylsulfinyl and heptylsulfinyl isomers. Examples of "alkylsulfonyl" include CH3S(=O)2, CH3CH2S(=O)2, CH3CH2CH2S(=O)2, (CH3)2CHS(=O)2, and the different butylsulfonyl, pentylsulfonyl, hexylsulfonyl and heptylsulfonyl isomers. "Alkylamino" includes an NH radical substituted with straight-chain or branched alkyl. Examples of "alkylamino" include CH3CH2NH, CH3CH2CH2NH, and (CH3)2CHCH2NH. Examples of "dialkylamino" include (CH3)2N, (CH3CH2CH2)2N and CH3CH2(CH3)N.
"Alkoxyalkyl" denotes alkoxy substitution on alkyl. Examples of "alkoxyalkyl" include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2CH2OCH2 and CH3CH2OCH2CH2. "Alkylthioalkyl" denotes alkylthio substitution on alkyl. Examples of "alkylthioalkyl" include CH3SCH2, CH3SCH2CH2, CH3CH2SCH2, CH3CH2CH2CH2SCH2 and CH3CH2SCH2CH2; "alkylsulfmylalkyl" and "alkylsulfonylalkyl" include the corresponding sulfoxides and sulfones, respectively. "(Alkylthio)carbonyl" denotes a straight-chain or branched alkylthio group bonded to a C(=O) moiety. Examples of "(alkylthio)carbonyl" include CH3SC(=O), CH3CH2CH2SC(=O) and (CH3)2CHSC(=O). "Alkoxy(thiocarbonyl)" denotes a straight-chain or branched alkoxy group bonded to a C(=S) moiety. Examples of "alkoxy(thiocarbonyl)" include CH3OC(=S),
CH3CH2CH2OC(=S) and (CH3)2CHOC(=S). "Alkylamino alkyl" denotes alkylamino substitution on alkyl. Examples of "alkylaminoalkyl" include CH3NHCH2, CH3NHCH2CH2, CH3CH2NHCH2, CH3CH2CH2CH2NHCH2 and CH3CH2NHCH2CH2. Examples of "dialkylaminoalkyl" include ((CH3)2CH)2NCH2, (CH3CH2CH2)2NCH2 and CH3CH2(CH3)NCH2CH2. The term "alkylcarbonylamino" denotes alkyl bonded to a C(=0)NH moiety. Examples of "alkylcarbonylamino" include CH3CH2C(=O)NH and CH3CH2CH2C(=O)NH.
"Hydroxyalkyl" denotes an alkyl group substituted with one hydroxy group. Examples of "hydroxyalkyl" include HOCH2CH2, CH3CH2(OH)CH and HOCH2CH2CH2CH2. "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. The term "alkylcycloalkyl" denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, z-propylcyclobutyl, methylcyclopentyl and methylcyclohexyl. The term "cycloalkylalkyl" denotes cycloalkyl substitution on an alkyl moiety. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups. The term "cycloalkylcycloalkyl" denotes cycloalkyl substitution on another cycloalkyl ring, wherein each cycloalkyl ring independently has from 3 to 7 carbon atom ring members. Examples of cycloalkylcycloalkyl include cyclopropylcyclopropyl (such as l,l'-bicyclopropyl-l-yl, 1,1'- bicyclopropyl-2-yl), cyclohexylcyclopentyl (such as 4-cyclopentylcyclohexyl) and cyclohexylcyclohexyl (such as l,l'-bicyclohexyl-l-yl), and the different cis- and trans- cycloalkylcycloalkyl isomers, (such as (li?,25)-l,l'-bicyclopropyl-2-yl and (\R,2R)-\,Y- bicyclopropyl-2-yl). The term "cycloalkoxy" denotes cycloalkyl attached to and linked through an oxygen atom including, for example, cyclopentyloxy and cyclohexyloxy. "Cycloalkylcarbonyl" denotes cycloalkyl bonded to a C(=O) group including, for example, cyclopropylcarbonyl and cyclopentylcarbonyl. The term "cycloalkoxycarbonyl" means cycloalkoxy bonded to a C(=O) group, for example, cyclopropyloxycarbonyl and cyclopentyloxycarbonyl. The term"cycloalkylene " denotes a cycloalkanediyl ring. Examples of "cycloalkylene" include cyclopropylene, cyclobutylene, cyclopentylene and cyclohexylene. The term "cycloalkenylene" denotes a cycloalkenediyl ring containing one olefmic bond. Examples of "cycloalkenylene" include cylopropenediyl and cyclpentenediyl.
Examples of "alkylene" include CH2, CH2CH2, CH(CH3), CH2CH2CH2,
CH2CH(CH3) and the different butylene, pentylene and hexylene isomers. "Alkylcarbonyl" denotes a straight-chain or branched alkyl bonded to a C(=O) moiety.
Examples of "alkylcarbonyl" include CH3C(=O), CH3CH2CH2C(=O) and (CH3)2CHC(=O). Examples of "alkoxycarbonyl" include CH3OC(=O), CH3CH2OC(=O), CH3CH2CH2OC(=O), (CH3)2CHOC(=O) and the different butoxy-, pentoxy-, hexoxy- and heptoxycarbonyl isomers. "Trialkylsilyl" includes 3 branched and/or straight-chain alkyl radicals attached to and linked through a silicon atom, such as trimethylsilyl, triethylsilyl and tert-butyldimethylsilyl.
The term "halogen", either alone or in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted with halogen" includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted with halogen" said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" or "alkyl substituted with halogen" include F3C, ClCH2, CF3CH2 and CF3CCl2. The terms "haloalkenyl", "haloalkoxy", "haloalkylthio", "haloalkylsulfmyl", "haloalkylsulfonyl", "halocycloalkyl", and the like, are defined analogously to the term "haloalkyl". Examples of "haloalkenyl" include Cl2C=CHCH2 and CF3CH2CH=CHCH2. Examples of "haloalkoxy" include CF3O, CCl3CH2O, F2CHCH2CH2O and CF3CH2O. Examples of "haloalkylthio" include CCl3S, CF3S, CCl3CH2S and ClCH2CH2CH2S. Examples of "haloalkylsulfmyl" include CF3S(=O), CC13S(=O), CF3CH2S(=O) and CF3CF2S(=O). Examples of "haloalkylsulfonyl" include CF3S(=O)2, CC13S(=O)2, CF3CH2S(=O)2 and CF3CF2S(=O)2. Examples of "halocycloalkyl" include
2-chlorocyclopropyl, 2-fluorocyclobutyl, 3-bromocyclopentyl and 4-chorocyclohexyl.
The total number of carbon atoms in a substituent group is indicated by the "Cj-Cj" prefix where i and j are numbers from 1 to 14. For example, C^-C4 alkylsulfonyl designates methylsulfonyl through butylsulfonyl; C2 alkoxyalkyl designates CH3OCH2; C3 alkoxyalkyl designates, for example, 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 CH3CH2CH2OCH2 and CH3CH2OCH2CH2. The term "unsubstituted" in connection with a group such as a ring or ring system means the group does not have any substituents other than its one or more attachments to the remainder of Formula 1. The term "optionally substituted" means that the number of substituents can be zero. Unless otherwise indicated, optionally substituted groups may be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom. Commonly, the number of optional substituents (when present) ranges from 1 to 3. As used herein, the term "optionally substituted" is used interchangeably with the phrase "substituted or unsubstituted" or with the term "(un)substituted."
The number of optional substituents may be restricted by an expressed limitation. For example, the phrase "optionally substituted with up to 3 substituents selected from R5a on carbon ring members" means that 0, 1, 2 or 3 substituents can be present (if the number of potential connection points allows). Similarly, the phrase "optionally substituted with up to 5 substituents selected from R5a on carbon ring members" means that 0, 1, 2, 3, 4 or 5 substituents can be present if the number of available connection points allows. When a range specified for the number of substituents (e.g., r being an integer from 0 to 5 in Exhibit 1) exceeds the number of positions available for substituents on a ring (e.g., 2 positions available for (Rv)r on A-11 in Exhibit 1), the actual higher end of the range is recognized to be the number of available positions.
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 (e.g., (Rv)r wherein r is 1, 2, 3, 4 or 5 in Exhibit 1). When a variable group is shown to be optionally attached to a position, for example (Rv)r wherein r may be 0, then hydrogen may be at the position even if not recited in the variable group definition. When one or more positions on a group are said to be "not substituted" or "unsubstituted", then hydrogen atoms are attached to take up any free valency.
Unless otherwise indicated, a "ring" as a component of Formula 1 is carbocyclic or heterocyclic. The term "ring system" as a component of Formula 1 denotes two fused rings (e.g., two phenyl rings fused to form naphthalenyl). The term "ring member" refers to an atom (e.g., C, O, N or S) or other moiety (e.g., C(=O), C(=S) or S(=O)p(=NR6)f) forming the backbone of a ring or ring system.
The term "nonaromatic" includes rings that are fully saturated as well as partially or fully unsaturated, provided that none of the rings are aromatic. In particular, a "fully unsaturated heterocycle" includes both aromatic and nonaromatic heterocycles. The term "aromatic" indicates that each of the ring atoms of a fully unsaturated ring is essentially in the same plane and has a /?-orbital perpendicular to the ring plane, and that (4n + T) π electrons, where n is a positive integer, are associated with the ring to comply with Hϋckel's rule.
The terms "carbocyclic ring", "carbocycle" or "carbocyclic ring system" denote a ring or ring system wherein the atoms forming the ring backbone are selected only from carbon. Unless otherwise indicated, a carbocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. When a fully unsaturated carbocyclic ring satisfies Hϋckel's rule, then said ring is also called an "aromatic carbocyclic ring". "Saturated carbocyclic" refers to a ring having a backbone consisting of carbon atoms linked to one another by single bonds; unless otherwise specified, the remaining carbon valences are occupied by hydrogen atoms.
The terms "heterocyclic ring" or "heterocycle" denote a ring in which at least one atom forming the ring backbone is not carbon (e.g., N, O or S). Typically a heterocyclic ring contains no more than 4 N atoms, no more than 2 O atoms and no more than 2 S atoms. Unless otherwise indicated, a heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. When a fully unsaturated heterocyclic ring satisfies Hϋckel's rule, then said ring is also called a "heteroaromatic ring" or "aromatic heterocyclic ring". The terms "heteroaromatic ring system" or "heteroaromatic bicyclic ring system" denote a ring system in which at least one atom forming the ring backbone is not carbon (e.g., N, O or S) and at least one ring is aromatic. Unless otherwise indicated, heterocyclic rings and heteroaromatic ring systems can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
In the context of the present invention when an instance of Q1, Q2 and Q3 comprises a phenyl or a 5- to 6-membered fully unsaturated heterocyclic ring, the ortho, meta and para positions of each ring is relative to the connection of the ring to the remainder of Formula 1. Further, when an instance of Q1, Q2 and Q3 comprises a phenyl or a 5- to 6-membered fully unsaturated heterocyclic ring attached through the linker CR7aR7b to the remained of Formula 1, the ortho, meta and para positions of each ring is relative to the connection of the ring to the linker CR7aR7b.
As noted above, each Q1, Q2 and Q3 is, inter alia, a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, each ring or ring system optionally substituted with up to 5 substituents independently selected from any substituent defined in the Summary of the Invention for Q1, Q2 and Q3 (e.g., a Q1 ring or ring system is optionally substituted with R5a on carbon ring members and cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members). As the substituents are optional, 0 to 5 substituents may be present, limited only by the number of available points of attachment. In this definition the ring members selected from up to 2 O, up to 2 S and up to 4 N atoms are optional, provided at least one ring member is not carbon (e.g., N, O or S). The definition of S(=O)p(=NR6)f allows the up to 2 sulfur ring members, to be oxidized sulfur moieties (e.g., S(=O) or S(=O)2) or unoxidized sulfur atoms (i.e. when p and f are both zero). The nitrogen atom ring members may be oxidized as //-oxides, because compounds relating to Formula 1 also include iV-oxide derivatives. The up to 3 carbon atom ring members selected from C(=O) and C(=S) are in addition to the up to 4 heteroatoms selected from up to 2 O, up to 2 S and up to 4 N atoms. Examples of a 5- to 6-membered fully unsaturated heterocyclic ring include the rings A-I through A-31 illustrated in Exhibit 1, and examples of an 8- to 10-membered heteroaromatic bicyclic ring system include the ring systems A-31 through A-72 illustrated in Exhibit 2. In Exhibits 1 and 2 the relative the variable (Rv)r is any substituent as defined in the Summary of the Invention for Q1, Q2 and Q3 (e.g., a Q1 ring or ring system is optionally substituted with R5a on carbon ring members and cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members) and r is an integer from 0 to 5, limited by the number of available positions on each depicted ring or ring system.
As noted above, each W1, W2 and W3 is, inter alia, a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, the ring optionally substituted with up to 5 substituents independently selected from any substituent defined in the Summary of the Invention for W1, W2 and W3 (e.g., a W1 ring is optionally substituted with R5a on carbon ring members and cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members). As the substituents are optional, 0 to 5 substituents may be present, limited only by the number of available points of attachment. In this definition the ring members selected from up to 2 O, up to 2 S and up to 4 N atoms are optional, provided at least one ring member is not carbon (e.g., N, O or S). The definition of S(=O)p(=NR6)f allows the up to 2 sulfur ring members, to be oxidized sulfur moieties (e.g., S(=O) or S(=O)2) or unoxidized sulfur atoms (i.e. when p and f are both zero). The nitrogen atom ring members may be oxidized as iV-oxides, because compounds relating to Formula 1 also include iV-oxide derivatives. The up to 2 carbon atom ring members selected from C(=O) and C(=S) are in addition to the up to 4 heteroatoms selected from up to 2 O, up to 2 S and up to 4 N atoms. Examples of a 5- to 6-membered fully unsaturated heterocyclic ring in W1, W2 and W3 include the rings A-I through A-31 illustrated in Exhibit 1 wherein (Rv)r is any substituent as defined in the Summary of the Invention for W1, W2 or W3 (e.g., a W1 ring is optionally substituted with R5a on carbon ring members and cyano, Cj-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members) and r is an integer from 0 to 5, limited by the number of available positions on each A-ring.
Although Rv groups are shown in the structures A-I through A-72, it is noted that they do not need to be present since they are optional substituents. Note that when Rv is H attached to an atom, this is the same as if said atom is unsubstituted. The nitrogen atoms that require substitution to fill their valence are substituted with H or Rv. Note that when the attachment point between (Rv)r and the depicted ring or ring system is illustrated as floating, (Rv)r can be attached to any available carbon atom or nitrogen atom of the depicted ring or ring system. Note that when the attachment point on the depicted ring or ring system is illustrated as floating, the depicted ring or ring system can be attached to the remainder of Formula 1 through any available carbon or nitrogen of the depicted ring or ring system by replacement of a hydrogen atom.
Exhibit 1
Figure imgf000014_0001
A-I A-2 A-3 A-4
Figure imgf000014_0002
A-5 A-6 A-7 A-8
Figure imgf000015_0001
A-9 A-IO A-I l A-12
Figure imgf000015_0002
A-13 A-14 A-15 A-16
Figure imgf000015_0003
A-17 A-18 A-19 A-20
Figure imgf000015_0004
A-21 A-22 A-23 A-24
Figure imgf000015_0005
A-25 A-26 A-27 A-28
Figure imgf000015_0006
A-29 A-30 A-31
Exhibit 2
Figure imgf000015_0007
Figure imgf000015_0008
A-34 A-35
Figure imgf000016_0001
6 A-37 A-38 A-39
Figure imgf000016_0002
A-64 A-65 A-66 A-67
Figure imgf000017_0001
A-72
A wide variety of synthetic methods are known in the art to enable preparation of aromatic heterocyclic rings and ring systems; for extensive reviews see the eight volume set of Comprehensive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees editors-in-chief, Pergamon Press, Oxford, 1984 and the twelve volume set of Comprehensive Heterocyclic Chemistry II, A. R. Katritzky, C. W. Rees and E. F. V. Scriven editors-in-chief, Pergamon Press, Oxford, 1996.
Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. 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 stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. The compounds of the invention may be present as a mixture of stereoisomers or as individual stereoisomers (e.g., in optically active form). Of note are atropisomers, which are conformational isomers that occur when rotation about a single bond in a molecule is restricted as a result of steric interaction with other parts of the molecule and the substituents at both ends of the single bond are unsymmetrical. In the present invention, atropisomerism occurs at a single bond in Formula 1 when the rotational barrier is high enough (about ΔG > 25 kcal moH) that separation of isomers at ambient temperature becomes possible. One skilled in the art will appreciate that one atropisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other atropisomer or when separated from the other atropisomer. Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said atropisomers. A detailed description of atropisomers can be found in March, Advanced Organic Chemistry, 4th Ed. 1992, 101-102 and Gawronski et al, Chirality 2002, 14, 689-702. This invention includes compounds or compositions that are enriched in an atropisomer of Formula 1 compared to other atropisomers of the compounds. Also included are the essentially pure atropisomers of compounds of Formula 1. One skilled in the art will appreciate that not all nitrogen-containing heterocycles can form JV-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen-containing heterocycles which can form TV-oxides. One skilled in the art will also recognize that tertiary amines can form JV-oxides. Synthetic methods for the preparation of iV-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for the preparation of iV-oxides have been extensively described and reviewed in the literature, see for example: T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A. R. Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, A. R. Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A. R. Katritzky and A. J. Boulton, Eds., Academic Press.
One skilled in the art recognizes that because in the environment and under physiological conditions salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms. Thus a wide variety of salts of the compounds of Formula 1 are useful for control of plant diseases caused by fungal plant pathogens (i.e. are agriculturally suitable). The salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids. Accordingly, the present invention comprises compounds selected from Formula 1, JV-oxides and agriculturally suitable salts thereof.
Compounds selected from Formula 1, geometric and other stereoisomers, iV-oxides, and salts thereof, typically exist in more than one form, and Formula 1 thus includes all crystalline and non-crystalline forms of the compounds that Formula 1 represents. 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 represented by Formula 1 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 represented by Formula 1. Preparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.
Embodiments of the present invention as described in the Summary of the Invention include those described below. In the following Embodiments, Formula 1 includes iV-oxides and salts thereof, and reference to "a compound of Formula 1" includes the definitions of substituents specified in the Summary of the Invention unless further defined in the
Embodiments.
Embodiment 1. A compound of Formula 1 wherein J is Q2. Embodiment 2. A compound of Formula 1 wherein J is R1.
Embodiment 3. A compound of Formula 1 or Embodiment 2 wherein R1 is C1-C3 alkyl. Embodiment 4. A compound of Embodiment 3 wherein R1 is methyl.
Embodiment 5. A compound of Formula 1 or any one of Embodiments 1 through 4 wherein X is CR2 or CQ3.
Embodiment 6. A compound of Embodiment 5 wherein X is CR2. Embodiment 6a. A compound of Embodiment 5 wherein X is CQ3. Embodiment 7. A compound of Formula 1 or any one of Embodiments 1 through 6a wherein Y is N. Embodiment 8. A compound of Formula 1 or any one of Embodiments 1 through 6a wherein Y is CR3.
Embodiment 9. A compound of Formula 1 or any one of Embodiments 1 through 8 wherein Z is CR4.
Embodiment 10. A compound of Formula 1 or any one of Embodiments 1 through 8 wherein Z is N.
Embodiment 11. A compound of Formula 1 wherein J is Q2, X is CR2, Y is N and Z is CR4, or J is R1, X is CQ3, Y is CR3 and Z is N, or J is Q2, X is CR2, Y is N and Z is N.
Embodiment 12. A compound of Embodiment 11 wherein J is Q2, X is CR2, Y is N and Z is CR4 or J is R1, X is CQ3, Y is CR3 and Z is N. Embodiment 13. A compound of Embodiment 12 wherein J is Q2, X is CR2, Y is N and
Z is CR4. Embodiment 14. A compound of Formula 1 or any one of Embodiments 1 through 13 wherein Q1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5a; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from up to 2 O, up to 2 S and up to 3 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)s(=NR6)f, the ring optionally substituted with up to 3 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W1.
Embodiment 15. A compound of Embodiment 14 wherein Q1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl,
C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W!. Embodiment 16. A compound of Embodiment 15 wherein Q1 is a phenyl or pyridinyl ring, optionally substituted with up to 3 substituents independently selected from
R5a.
Embodiment 17. A compound of Embodiment 16 wherein Q1 is a pyridinyl ring attached to Formula 1 at the 3 -position of the pyridinyl ring and optionally substituted with up to 3 substituents independently selected from R5a. Embodiment 18. A compound of Embodiment 16 wherein Q1 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R5a. Embodiment 19. A compound of Formula 1 or any one of Embodiments 1 through 15 wherein W1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members. Embodiment 20. A compound of Embodiment 19 wherein W1 is a phenyl or pyridinyl ring, optionally substituted with up to 3 substituents independently selected from R5a.
Embodiment 21. A compound of Embodiment 20 wherein W1 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R5a.
Embodiment 22. A compound of Formula 1 or any one of Embodiments 1 through 21 wherein Q2 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5b; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from up to 2 O, up to 2 S and up to 3 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)s(=NR6)f, the ring optionally substituted with up to 3 substituents independently selected from R5^ on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W2.
Embodiment 23. A compound of Embodiment 22 wherein Q2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5^ on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W2.
Embodiment 24. A compound of Embodiment 23 wherein Q2 is a phenyl or pyridinyl ring, optionally substituted with up to 3 substituents independently selected from R5b. Embodiment 25. A compound of Embodiment 24 wherein Q2 is a pyridinyl ring attached to Formula 1 at the 3 -position of the pyridinyl ring and optionally substituted with up to 3 substituents independently selected from R5^. Embodiment 26. A compound of Embodiment 24 wherein Q2 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R5^. Embodiment 27. A compound of Formula 1 or any one of Embodiments 1 through 26 wherein when each Q1 and Q2 is independently a phenyl or pyridinyl ring, then one of the Q1 and Q2 rings is substituted with 2 or 3 substituents and the other of the Q1 and Q2 rings is substituted with 1 or 3 substituents. Embodiment 27a. A compound of Formula 1 or any one of Embodiments 1 through 27 wherein when each Q1 and Q2 is independently a phenyl or pyridinyl ring, then one of the Q1 and Q2 rings is substituted with 2 or 3 substituents and the other of the Q1 and Q2 rings is substituted with 1 or 2 substituents. Embodiment 28. A compound of Formula 1 or any one of Embodiments 1 through 27 wherein at least one R5a substituent is attached at an ortho position of the Q1 ring.
Embodiment 29. A compound of Formula 1 or any one of Embodiments 1 through 28 wherein two R5a substituents are attached at ortho positions of the Q1 ring. Embodiment 30. A compound of Formula 1 or any one of Embodiments 1 through 29 wherein at least one R5^ substituent is attached at an ortho position of the Q2 ring.
Embodiment 31. A compound of Formula 1 or any one of Embodiments 1 through 30 wherein two R5^ substituents are attached at ortho positions of the Q2 ring. Embodiment 32. A compound of Formula 1 or any one of Embodiments 1 through 23 wherein W2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R5b on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members.
Embodiment 33. A compound of Embodiment 32 wherein W2 is a phenyl or pyridinyl ring, optionally substituted with up to 3 substituents independently selected from R5b. Embodiment 34. A compound of Embodiment 33 wherein W2 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R5^. Embodiment 35. A compound of Formula 1 or any one of Embodiments 1 through 34 wherein Q3 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5c; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from up to 2 O, up to 2 S and up to 3 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)s(=NR6)f,the ring optionally substituted with up to 3 substituents independently selected from
R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W3.
Embodiment 36. A compound of Embodiment 35 wherein Q3 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W3.
Embodiment 37. A compound of Embodiment 36 wherein Q3 is a phenyl or pyridinyl ring, optionally substituted with up to 3 substituents independently selected from R5c.
Embodiment 38. A compound of Embodiment 37 wherein Q3 is a pyridinyl ring attached to Formula 1 at the 3 -position of the pyridinyl ring and optionally substituted with up to 3 substituents independently selected from R5c. Embodiment 39. A compound of Embodiment 37 wherein Q3 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R5c. Embodiment 40. A compound of Formula 1 or any one of Embodiments 1 through 36 wherein W3 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members.
Embodiment 41. A compound of Embodiment 40 wherein W3 is a phenyl or pyridinyl ring, optionally substituted with up to 3 substituents independently selected from R5C.
Embodiment 42. A compound of Embodiment 41 wherein W3 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R5c.
Embodiment 43. A compound of Formula 1 or any one of Embodiments 1 through 42 wherein each R2, R3 and R4 is independently H, halogen, C2-C3 alkenyl, C2-C3 alkynyl, C2-C3 haloalkenyl, C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C3 alkylthio, C1-C3 alkylamino, C2-C4 dialkylamino or C1-C3 hydroxyalkyl; or C1-C3 alkyl or C1-C3 haloalkyl, each optionally substituted with up to 1 substituent independently selected from hydroxy, cyano, C(=O)OR8, C(=O)NR9aR9b, C(O)R10 and CH=NOR11. Embodiment 44. A compound of Embodiment 43 wherein each R2, R3 and R4 is independently H, halogen, cyano or C1-C3 alkyl. Embodiment 45. A compound of Embodiment 44 wherein each R2, R3 and R4 is independently Cl, Br, I or C1-C2 alkyl. Embodiment 46. A compound of Embodiment 45 wherein each R2, R3 and R4 is independently Cl, Br or methyl. Embodiment 47. A compound of Formula 1 or any one of Embodiments 1 through 46 wherein each R5a, R5^ and R5c is independently halogen, cyano, C1-C3 alkyl,
C2-C3 alkenyl, C2-C3 alkynyl, C1-C3 haloalkyl, C3 cycloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylamino, C2-C4 dialkylamino
C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonylamino or
-U-V-T. Embodiment 48. A compound of Embodiment 47 wherein each R5a, R5^ and R5c is independently halogen, cyano, C1-C3 alkyl, C2-C3 alkenyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 alkylthio or C1-C3 alkylamino.
Embodiment 49. A compound of Embodiment 48 wherein each R5a, R5^ and R5c is independently halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl or C1-C3 alkoxy. Embodiment 50. A compound of Embodiment 49 wherein each R5a, R5^ and R5c is independently F, Cl, Br, cyano, C1-C2 alkyl, C1-C2 haloalkyl or C1-C2 alkoxy. Embodiment 51. A compound of Embodiment 50 wherein each R5a, R5^ and R5c is independently F, Cl, cyano, methyl, trifluoromethyl or methoxy. Embodiment 52. A compound of Formula 1 or any one of Embodiments 1 through 47 wherein each U is independently O or NR12.
Embodiment 53. A compound of Embodiment 52 wherein each U is independently O or NH.
Embodiment 54. A compound of Formula 1 or any one of Embodiments 1 through 47 wherein each V is C2-C4 alkylene. Embodiment 55. A compound of Formula 1 or any one of Embodiments 1 through 47 wherein each T is independently NR13aR13b or OR14. Embodiment 55 a. A compound of Formula 1 or any one of Embodiments 1 through 55 wherein each R13a and R13^ is independently H, C1-C6 alkyl or C1-C6 haloalkyl. Embodiment 55b. A compound of Formula 1 or any one of Embodiments 1 through 55 wherein each R14 is independently H, C1-C6 alkyl or C1-C6 haloalkyl. Embodiment 56. A compound of Formula 1 or any one of Embodiments 1 through 55b independently when an instance of R7a is not taken together with the carbon atom to which the instance of R7a is attached and a geminal instance of R7^ to form a carbocyclic ring (i.e. R7a is taken alone) then the instance of R7a is H, cyano or methyl. Embodiment 56a. A compound of Embodiment 56 wherein each R7a is independently H or methyl.
Embodiment 57. A compound of Embodiment 56a wherein each R7a is H.
Embodiment 58. A compound of Formula 1 or any one of Embodiments 1 through 57 wherein independently when an instance of R7^ is not taken together with the carbon atom to which the instance of R7^ is attached and a geminal instance of R7a to form a carbocyclic ring (i.e. R7^ is taken alone) then the instance of R7^ is independently H or methyl.
Embodiment 59. A compound of Embodiment 58 wherein each R7^ is H. Embodiment 59a. A compound of Formula 1 or any one of Embodiments 1 through 59 wherein when a pair of R7a and R7^ attached to the same carbon atom are taken together with the carbon atom to form a carbocyclic ring, the ring is a cyclopropyl ring.
Embodiment 60. A compound of Formula 1 or any one of Embodiments 1 through 59a wherein each pair of R7a and R7^ attached to the same carbon atom are not taken together to form a carbocyclic ring (i.e. R7a and R7^ are taken alone).
Embodiment 61. A compound of Formula 1 or any one of Embodiments 1 through 60 wherein each R8, R9a, R9b, R10 and R11 is independently H, C1-C2 alkyl, C2-C3 alkenyl, C2-C3 alkynyl or C1-C2 haloalkyl. Embodiment 62. A compound of Embodiment 61 wherein each R8, R9a, R9^, Rl° and
R1 * is independently H or methyl.
Embodiment 63. A compound of Formula 1 or any one of Embodiments 1 through 62 wherein when J is Q2, X is CR2, Y is N and Z is CR4 and Q1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5a; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5a on carbon atom ring members and selected from cyano, Cj -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, Q-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members, R4 is halogen and Q2 is a 2-pyridinyl ring substituted with halogen at an ortho position, then said 2-pyridinyl ring is also substituted with R5^ at a meta position; provided that when Q2 is a phenyl ring substituted with halogen at an ortho position and Q1 is neither phenyl nor substituted phenyl, then said Q2 phenyl ring is also substituted with R5^ at at least one meta position. Embodiment 63a. A compound of Formula 1 or any one Embodiments 1 through 62 wherein when J is Q2, X is CR2, Y is N and Z is CR4 and Q1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5a; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2
O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C ^ -C6 alkyl,
C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, Q-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members, R4 is halogen and Q2 is a phenyl ring or 2-pyridinyl ring substituted with halogen at an ortho position, then said phenyl ring or 2-pyridinyl ring is also substituted with R5^ at a meta position. Embodiment 64. A compound of Formula 1 or any one Embodiments 1 through 62 wherein when J is Q2, X is CR2, Y is N and Z is CR4 and Q2 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5b; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5b on carbon atom ring members and selected from cyano, C^-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C^-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members, R2 is halogen and Q1 is a 2-pyridinyl ring substituted with halogen at an ortho position, then said 2-pyridinyl ring is also substituted with R5a at a meta position; provided that when Q1 is phenyl ring substituted with halogen at an ortho position and Q2 is neither phenyl nor substituted phenyl, then said Q1 phenyl ring is also substituted with R5a at at least one meta position. Embodiment 64a. A compound of Formula 1 or any one Embodiments 1 through 62 wherein when J is Q2, X is CR2, Y is N and Z is CR4 and Q2 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5b; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2
O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5b on carbon atom ring members and selected from cyano, Q-C6 alkyl,
C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, Q-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members and R2 is halogen and Q1 is a phenyl ring or 2-pyridinyl ring substituted with halogen at an ortho position, then said phenyl ring or 2-pyridinyl ring is also substituted with R5a at a meta position;
Embodiment 65. A compound of Formula 1 or any one of Embodiments 1 through 62 wherein when J is Q2, X is CR2, Y is N and Z is CR4, then
(a) when Q2 is an optionally substituted phenyl ring, an optionally substituted naphthalenyl ring system, an optionally substituted fully unsaturated heterocyclic ring, or an optionally substituted heteroaromatic bicyclic ring system, and R2 is halogen:
(i) when Q1 is a 2-pyridinyl ring substituted with halogen at an ortho position, then said 2-pyridinyl ring is also substituted with R5a at at least one meta position, and
(ii) when Q1 is phenyl ring substituted with halogen at an ortho position and Q2 is neither phenyl nor substituted phenyl, then said Q1 phenyl ring is also substituted with R5a at at least one meta position; and
(b) when Q1 is an optionally substituted phenyl ring, an optionally substituted naphthalenyl ring system, an optionally substituted fully unsaturated heterocyclic ring, or an optionally substituted heteroaromatic bicyclic ring system, and R4 is halogen: (i) when Q2 is a 2-pyridinyl ring substituted with halogen at an ortho position, said 2-pyridinyl ring is also substituted with R5^ at at least one meta position, and
(ii) when Q2 is a phenyl ring substituted with halogen at the ortho position and Q1 is neither phenyl nor substituted phenyl, then said Q2 phenyl ring is also substituted with R5^ at at least one meta position.
Embodiment 65 a. A compound of Formula 1 of Embodiment 65 wherein when R2 is halogen and Q1 is a phenyl ring substituted with halogen at an ortho position, then Q2 is neither phenyl nor substituted phenyl; and when R4 is halogen and Q2 is a phenyl ring substituted with halogen at an ortho position, then Q1 is neither phenyl nor substituted phenyl.
Embodiments of this invention, including Embodiments l-65a above as well as any other embodiments described herein, can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds useful for preparing the compounds of Formula 1. In addition, embodiments of this invention, including Embodiments l-65a above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention.
Combinations of Embodiments l-65a are illustrated by: Embodiment Al . A compound of Formula 1 wherein
Q1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5a; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from up to 2 O, up to 2 S and up to
3 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)s(=NR6)f, the ring optionally substituted with up to 3 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W!; W1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members;
Q2 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5b; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from up to 2 O, up to 2 S and up to 3 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)s(=NR6)f, the ring optionally substituted with up to 3 substituents independently selected from R5b on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W2;
W2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R5b on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; Q3 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5c; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from up to 2 O, up to 2 S and up to 3 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)s(=NR6)f, the ring optionally substituted with up to 3 substituents independently selected from R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy,
C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W3; W3 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; each R7a is independently H, cyano or methyl; each R7b is independently H or methyl; or a pair of R7a and R7b attached to the same carbon atom are taken together with the carbon atom to form a cyclopropyl ring; Embodiment A2. A compound of Embodiment Al wherein
Q1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W!;
W1 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5a; Q2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5b on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W2;
W2 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5b; Q3 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W3; W3 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5c; each R2, R3 and R4 is independently H, halogen, C2-C3 alkenyl, C2-C3 alkynyl, C2-C3 haloalkenyl, C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C3 alkylthio, C1-C3 alkylamino, C2-C4 dialkylamino or C1-C3 hydroxyalkyl; or C1-C3 alkyl or C1-C3 haloalkyl, each optionally substituted with up to 1 substituent independently selected from hydroxy, cyano, C(=O)OR8, C(=O)NR9aR9b, Q=O)R1 ° and
CH=NOR11; each R5a, R5b and R5c is independently halogen, cyano, C1-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, C1-C3 haloalkyl, C3 cycloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylamino, C2-C4 dialkylamino C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonylamino or -U-V-T; U is O or NH; V is C2-C4 alkylene; T is NR13aR13b or OR14; each R7a and R7b is independently H or methyl; each R8, R9a, R9b, R10 and R11 is independently H or methyl; each R13a and R13b is independently H, C1-C6 alkyl or C1-C6 haloalkyl; and each R14 is independently H, C1-C6 alkyl or C1-C6 haloalkyl. Embodiment A3. A compound of Embodiment A2 wherein Q1 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5a; Q2 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5b; and Q3 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5c.
Embodiment A4. A compound of Embodiment A3 wherein each R2, R3 and R4 is independently H, halogen, cyano or C1-C3 alkyl; and each R5a, R5b and R5c is independently halogen, cyano, C1-C3 alkyl, C2-C3 alkenyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 alkylthio or C1-C3 alkylamino.
Embodiment A5. A compound of Embodiment A4 wherein J is Q2; X is CR2; Y is N;
Z is CR4; each R2 and R4 is independently Cl, Br, I or C1-C2 alkyl; each R5a and R5b is independently F, Cl, Br, cyano, C1-C2 alkyl, C1-C2 haloalkyl or C1-C2 alkoxy; and one of the Q1 and Q2 rings is substituted with 2 to 3 substituents and the other of the Q1 and Q2 rings is substituted with 1 to 2 substituents.
Specific embodiments include compounds of Formula 1 selected from the group consisting of:
4-chloro- 1 -(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)- lH-imidazole; 4-chloro- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl- lH-imidazole; 2,4-dichloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2,4-dimethyl-lH-imidazole; 4-chloro- 1 -(4-chlorophenyl)-2-methyl-5-(2,4,6-trifluorophenyl)- lH-imidazole; l-(4-chlorophenyl)-2,4-dimethyl-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-2,4-dichloro-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl-lH- imidazole; l-(4-chlorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazole; 4-chloro- l-(4-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH- imidazole;
4-chloro- 1 -(4-chloro-3-fluorophenyl)-2-methyl-5-(2,4,6-trifluorophenyl)- IH- imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dimethyl-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chloro-3-fluorophenyl)-5-(2,6-difluorophenyl)-2,4-dimethyl-lH-imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,6-difluorophenyl)-lH-imidazole; 4-chloro- l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2- methyl- lH-imidazole; l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl-lH- imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH- imidazole;
4-chloro- 1 -(3-fluorophenyl)-2-methyl-5-(2,4,6-trifluorophenyl)- lH-imidazole; 2,4-dichloro- 1 -(3-fluorophenyl)-5-(2,4,6-trifluorophenyl)- lH-imidazole; 4-chloro- 1 -(3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl- IH- imidazole; l-(3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl-lH- imidazole; l-(3-fluorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazole;
4-chloro-l-(4-chlorophenyl)-2-methyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-2,4-dimethyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-2,4-dichloro-5-(2,3,6-trifluorophenyl)-lH-imidazole;
4-chloro-l-(3-fluorophenyl)-2-methyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(3-fluorophenyl)-2,4-dimethyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(3-fluorophenyl)-2,4-dichloro-5-(2,3,6-trifluorophenyl)-lH-imidazole;
4-chloro-5-(2-chloro-4-fluorophenyl)- 1 -(4-chlorophenyl)-2-methyl- lH-imidazole;
5-(2-chloro-4-fluorophenyl)-l-(4-chlorophenyl)-2,4-dimethyl-lH-imidazole;
5-(2-chloro-4-fluorophenyl)-l-(4-chlorophenyl)-2,4-dichloro-lH-imidazole;
4-chloro-l-(4-chlorophenyl)-5-(2,6-difluoro-3-methoxyphenyl)-2-methyl-lH- imidazole;
4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(4-fluorophenyl)-2-methyl- IH- imidazole;
4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-l-(4-methylphenyl)-lH- imidazole;
4-[4-chloro-l-(4-chlorophenyl)-2-methyl-lH-imidazol-5-yl]-3,5- difluorobenzonitrile;
2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3-fluorophenyl)-lH- imidazole;
2-chloro-l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-4- methyl- lH-imidazole;
2-chloro-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol-l- yl]pyridine;
2-bromo-4-chloro-5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluorophenyl)-lH- imidazole;
4-chloro-5-(2,6-difluoro-3-methoxyphenyl)-2-methyl-l-(4-methylphenyl)-lH- imidazole;
4-chloro-5-(2,6-difluro-3-methoxyphenyl)- 1 -(4-fluorophenyl)-2 -methyl- IH- imidazole;
2,4-dichloro-5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluorophenyl)-lH-imidazole;
2,4-dichloro-l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-3-methoxyphenyl)-lH- imidazole;
4-chloro-l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-3-methoxyphenyl)-2- methyl- lH-imidazole;
2-chloro-5-[2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 - yl]pyridine; 4-chloro-l-[3-(difluoromethoxy)phenyl]-5-(2,6-difluoro-3-methoxyphenyl)-2- methyl- lH-imidazole;
3-[4-chloro-l-(4-chlorophenyl)-2-methyl-lH-imidazol-5-yl]-2,4- difluorobenzonitrile;
4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3,4-difluorophenyl)-2-methyl-lH- imidazole;
4-chloro-l-(3-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH- imidazole;
4-bromo-2-chloro-l-(4-chlorophenyl)-5-(2,6-difluoro-3-methoxyphenyl)-lH- imidazole;
5-[2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-yl]-2- methylpyridine;
5-[2,4-dibromo-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 -yl]-2- methylpyridine;
2-chloro-5-(4-chlorophenyl)-l-(2,6-difluoro-4-methoxyphenyl)-4-methyl- imidazole;
4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluorophenyl)-lH-imidazole-2- carboxaldehyde oxime;
4-chloro-l-(2,6-dichlorophenyl)-2-methyl-5-[(2,4,6-trifluorophenyl)methyl]-lH- imidazole;
2-chloro-5-[2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 -yl-4- methyljpyridine;
4-(2-chloro-4-fluorophenyl)-5-[(2,4-difluorophenyl)methyl]-l,3-dimethyl-lH- pyrazole; and
2-chloro- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)-4-methyl- lH-imidazole;
2-chloro- 1 -(4-chlorophenyl)-4-methyl-5-(2,4,6-trifluorophenyl)- lH-imidazole;
2-chloro- l-(4-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH- imidazole;
2-chloro- 1 -(4-chloro-3-fluorophenyl)-4-methyl-5-(2,4,6-trifluorophenyl)- IH- imidazole;
2-chloro- l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-4- methyl- lH-imidazole;
2-chloro- 1 -(3-fluorophenyl)-4-methyl-5-(2,4,6-trifluorophenyl)- lH-imidazole;
2-chloro- 1 -(3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl- IH- imidazole;
2-chloro- l-(4-chlorophenyl)-4-methyl-5-(2,3,6-trifluorophenyl)-lH-imidazole;
2-chloro- l-(3-fluorophenyl)-4-methyl-5-(2,3,6-trifluorophenyl)-lH-imidazole;
2-chloro- l-(4-chlorophenyl)-5-(2,6-difluoro-3-methyoxyphenyl)-4-methyl-lH- imidazole;
2-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(4-fluorolphenyl)-4-methyl- IH- imidazole;
2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-l-(4-methylphenyl)-lH- imidazole;
4-[2-chloro-l-(4-chlorophenyl)-4-methyl-lH-imidazol-5-yl]-3,5- difluorobenzonitrile;
2-chloro-5-(2,6-difluoro-3-methoxyphenyl)-4-methyl-l-(4-methylphenyl)-lH- imidazole;
2-chloro-5-(2,6-difluoro-3-methoxyphenyl)- 1 -(4-fluorophenyl)-4-methyl- IH- imidazole;
2-chloro-l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-3-methoxyphenyl)-lH- imidazole;
2-chloro-l-[3-(difluoromethoxy)phenyl]-5-(2,6-difluoro-3-methoxyphenyl)-4- methyl- lH-imidazole;
3-[2-chloro-l-(4-chlorophenyl)-4-methyl-lH-imidazol-5-yl]-2,4- difluorobenzonitrile;
2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3,4-difluorophenyl)-4-methyl-lH- imidazole;
2-chloro-l-(3-chlorophenyl)-5-(2,6-difluoro-4-methoxphenyl)-4-methyl-lH- imidazole;
2-fluoro-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol-l- yl]pyridine;
2-bromo-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl- lH-imidazol- 1 - yl]pyridine;
2-methoxy-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol- l-yl]pyridine;
2-trifluoromethoxy-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH- imidazol- 1 -yl]pyridine;
2-trifluoromethyl-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH- imidazol- 1 -yl]pyridine;
2-cyano-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol-l- yl]pyridine;
3-fluoro-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol-l- yl]pyridine;
3-bromo-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl- lH-imidazol- 1 - yl]pyridine;
3-chloro-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol-l- yl]pyridine;
3-methoxy-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol- l-yl]pyridine; l-(4-chlorophenyl)-5-(2,6-difluoro-4-ethoxyphenyl)-2,4-dimethyl-lH-imidazole; l-(4-fluorophenyl)-5-(2,6-difluoro-4-ethoxyphenyl)-2,4-dimethyl-lH-imidazole; l-(3-chlorophenyl)-5-(2,6-difluoro-4-ethoxyphenyl)-2,4-dimethyl-lH-imidazole; l-(3-fluorophenyl)-5-(2,6-difluoro-4-ethoxyphenyl)-2,4-dimethyl-lH-imidazole;
1 -(4-methylphenyl)-5-(2,6-difluoro-4-ethoxyphenyl)-2,4-dimethyl- lH-imidazole; and l-(3-methylphenyl)-5-(2,6-difluoro-4-ethoxyphenyl)-2,4-dimethyl-lH-imidazole.
Another aspect of the present invention relates to compounds of Formula IP (including all geometric and stereoisomers), iV-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides:
Y—x
N ^
J
IP wherein
J iS Q2 Or R1; X is N, CR2 Or CQ3; Y is N or CR3; Z is N or CR4; Q1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5a; Q2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5b;
Q3 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5c;
R1 is C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C7 cycloalkyl, C1-C7 haloalkyl, C2-C7 haloalkenyl, C^C1Q alkylcycloalkyl or C^C1Q cycloalkylalkyl; each R2, R3 and R4 is independently Η, halogen, cyano, nitro, C1-C7 alkyl, C2-C7 alkenyl, C7-C7 alkynyl, C3-C7 cycloalkyl, C1-C7 haloalkyl, C2-C7 haloalkenyl, C1-C7 alkoxy, C1-C7 haloalkoxy, C1-C7 alkylthio, C1-C7 alkylsulfmyl, C1-C7 alkylsulfonyl, C1-C7 haloalkylthio, C1-C7 haloalkylsulfmyl, C1-C7 haloalkylsulfonyl, C1-C7 alkylamino or C2-C7 dialkylamino; and each R5a, R5b and R5c is independently halogen, cyano, nitro, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C7 cycloalkyl, C1-C7 haloalkyl, C2-C7 haloalkenyl, C1-C7 alkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C7 haloalkoxy, C1-C7 haloalkylthio, C1-C7 haloalkylsulfmyl, C1-C7 haloalkylsulfonyl, C1-C7 alkylamino, C2-C7 dialkylamino, C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl or C3-C1Q trialkylsilyl; provided that: (a) when J is R1, then X is CQ3;
(b) when J is Q2, then X is N or CR2, and if X is N or CH, then Z is other than CH; and
(c) when Q1 is a phenyl ring which is not substituted by R5a at either ortho positions, then when X is N or CR2 and Q2 is a phenyl ring, the Q2 phenyl ring is substituted by at least one R5b at an ortho position; and when X is CQ3 and Q3 is a phenyl ring, the Q3 phenyl ring is substituted by at least one R5c at an ortho position.
One skilled in the art recognizes that the definition of substituents on Formula IP overlap the definition of substituents on Formula 1 as described in the Summary of the Invention and therefore disclosure herein relative to Formula 1 also extends to Formula IP.
More particularly, this aspect of the present invention pertains to a compound of Formula IP (including all geometric and stereoisomers), an JV-oxide or a salt thereof.
Related to this aspect is a fungicidal composition comprising (a) a compound selected from Formula IP, //-oxides and salts thereof; and (b) at least one other fungicide. Also related to this aspect is a fungicidal composition comprising (a) a fungicidally effective amount of a compound selected from Formula IP, //-oxides and salts thereof; and (b) at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
Also related to this aspect is a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound selected from Formula IP, JV-oxides and salts thereof (e.g., as a composition described herein).
Embodiments of this aspect include Embodiments Bl through B53 described below. In the following Embodiments, Formula IP includes iV-oxides and salts thereof, and reference to "a compound of Formula IP" includes the definitions of substituents specified above for Formula IP unless further defined in the Embodiments. Embodiment B 1. A compound of Formula IP wherein J is Q2. Embodiment B2. A compound of Formula IP wherein J is R1. Embodiment B3. A compound of Formula IP or Embodiment Bl wherein R1 is C1-C2 alkyl.
Embodiment B4. A compound of Formula IP wherein X is CR2. Embodiment B5. A compound of Formula IP wherein X is CQ3. Embodiment B6. A compound of Formula IP wherein Y is N.
Embodiment B7. A compound of Formula IP wherein Y is CR3. Embodiment B8. A compound of Formula IP wherein Z is CR4. Embodiment B9. A compound of Formula IP wherein Z is N. Embodiment BlO. A compound of Formula IP wherein Q1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5a. Embodiment B 11. A compound of Formula IP wherein Q2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5^. Embodiment B 12. A compound of Formula IP wherein Q3 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5c.
Embodiment B 13. A compound of Embodiment BlO wherein Q1 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R5a. Embodiment B 14. A compound of Embodiment BI l wherein Q2 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R5^ Embodiment B 15. A compound of Embodiment B 12 wherein Q3 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R5c. Embodiment B 16. A compound of Embodiment B13 wherein Q1 is a phenyl ring optionally substituted with up to 2 substituents independently selected from R5a. Embodiment B 17. A compound of Embodiment B 14 wherein Q2 is a phenyl ring optionally substituted with up to 2 substituents independently selected from R5^.
Embodiment B 18. A compound of Embodiment B15 wherein Q3 is a phenyl ring optionally substituted with up to 2 substituents independently selected from R5c. Embodiment B 19. A compound of Embodiment B16 wherein Q1 is a phenyl ring optionally substituted with up to 1 substituent selected from R5a. Embodiment B20. A compound of Embodiment B17 wherein Q2 is a phenyl ring optionally substituted with up to 1 substituent selected from R5^. Embodiment B21. A compound of Embodiment Bl 8 wherein Q3 is a phenyl ring optionally substituted with up to 1 substituent selected from R5c. Embodiment B22. A compound of Formula IP or Embodiment B13 wherein Q1 is a phenyl ring substituted with up to 3 substituents independently selected from R5a attached at ortho and/or para positions.
Embodiment B23. A compound of Formula IP or Embodiment B 14 wherein Q2 is a phenyl ring substituted with up to 3 substituents independently selected from R5b attached at ortho and/or para positions. Embodiment B24. A compound of Formula IP or Embodiment B 15 wherein Q3 is a phenyl ring substituted with up to 3 substituents independently selected from R5c attached at ortho and/or para positions. Embodiment B25. A compound of Formula IP or Embodiment B22 wherein Q1 is a phenyl ring substituted with 3 substituents independently selected from R5a attached at ortho and para positions. Embodiment B26. A compound of Formula IP or Embodiment B23 wherein Q2 is a phenyl ring substituted with 3 substituents independently selected from R5b attached at ortho and para positions.
Embodiment B27. A compound of Formula IP or Embodiment B24 wherein Q3 is a phenyl ring substituted with 3 substituents independently selected from R5c attached at ortho and para positions.
Embodiment B28. A compound of Formula IP or Embodiment B22 wherein Q1 is a phenyl ring substituted with up to 2 substituents independently selected from R5a attached at ortho and/or para positions. Embodiment B29. A compound of Formula IP or Embodiment B23 wherein Q2 is a phenyl ring substituted with up to 2 substituents independently selected from R5b attached at ortho and/or para positions. Embodiment B30. A compound of Formula IP or Embodiment B24 wherein Q3 is a phenyl ring substituted with up to 2 substituents independently selected R5c attached at ortho and/or para positions. Embodiment B31. A compound of Formula IP or Embodiment B28 wherein Q1 is a phenyl ring substituted with 2 substituents independently selected from R5a attached at one ortho position and the para position.
Embodiment B32. A compound of Formula IP or Embodiment B29 wherein Q2 is a phenyl ring substituted with 2 substituents independently selected from R5b attached at one ortho position and the para position.
Embodiment B33. A compound of Formula IP or Embodiment B30 wherein Q3 is a phenyl ring substituted with 2 substituents independently selected from R5c attached at one ortho position and the para position. Embodiment B34. A compound of Formula IP or Embodiment B28 wherein Q1 is a phenyl ring substituted with 2 substituents independently selected from R5a attached at ortho positions.
Embodiment B35. A compound of Formula IP or Embodiment B29 wherein Q2 is a phenyl ring substituted with 2 substituents independently selected from R5^ attached at ortho positions. Embodiment B36. A compound of Formula IP or Embodiment B30 wherein Q3 is a phenyl ring substituted with 2 substituents independently selected from R5c attached at ortho positions. Embodiment B37. A compound of Formula IP wherein Q1 is a phenyl ring substituted with 2 substituents independently selected from R5a attached at one meta position and the para position. Embodiment B38. A compound of Formula IP wherein Q2 is a phenyl ring substituted with 2 substituents independently selected from R5^ attached at one meta position and the para position.
Embodiment B39. A compound of Formula IP wherein Q3 is a phenyl ring substituted with 2 substituents independently selected from R5c attached at one meta position and the para position.
Embodiment B40. A compound of Formula IP or Embodiment B 19 wherein Ql is a phenyl ring substituted with up to 1 substituent selected from R5a attached at the para position. Embodiment B41. A compound of Formula IP or Embodiment B21 wherein Q^ is a phenyl ring substituted with up to 1 substituent selected from R5c attached at the para position. Embodiment B42. A compound of Formula IP or Embodiment B40 wherein Q1 is a phenyl ring substituted with 1 substituent selected from R5a attached at the para position. Embodiment B43. A compound of Formula IP wherein Q2 is a phenyl ring substituted with 1 substituent selected from R5^ attached at the para position. Embodiment B44. A compound of Formula IP or Embodiment B41 wherein Q3 is a phenyl ring substituted with 1 substituent selected from R5c attached at the para position. Embodiment B45. A compound of Formula IP wherein each R2, R3 and R4 is independently H, halogen, cyano, C1-C3 alkyl, C2-C3 alkenyl, C3 cycloalkyl or C1-C3 haloalkyl.
Embodiment B46. A compound of Embodiment B45 wherein each R2, R3 and R4 is independently H, halogen or C1-C3 alkyl. Embodiment B47. A compound of Embodiment B46 wherein each R2, R3 and R4 is independently H, Cl, Br, I or C1-C2 alkyl. Embodiment B48. A compound of Embodiment B47 wherein R2 is selected from H, Cl,
Br, I and C1-C2 alkyl. Embodiment B49. A compound of Embodiment B47 wherein R3 is selected from H, Cl,
Br or CH3; Embodiment B50. A compound of Embodiment B47 wherein R4 is selected from H, Cl,
Br or CH3.
Embodiment B51. A compound of Formula IP wherein each R5a, R5^ and R5c is independently halogen, cyano, nitro, C1-C3 alkyl, C2-C3 alkenyl, C3 cycloalkyl,
C1-C3 haloalkyl, C2-C3 haloalkenyl, C1-C3 alkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 haloalkoxy or C1-C6 haloalkylthio.
Embodiment B52. A compound of Embodiment B51 wherein each R5a, R5^ and R5c is independently halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl or C1-C3 alkoxy. Embodiment B53. A compound of Embodiment B52 wherein each R5a, R5^ and R5c is independently halogen, CH3, OCH3 or CF3.
Embodiments B1-B53 above as well as any other embodiments described herein relevant to Formula IP, can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula IP but also to the starting compounds and intermediate compounds useful for preparing the compounds of Formula IP. In addition, Embodiments B1-B53 above as well as any other embodiments described herein relevant to Formula IP, and any combination thereof, pertain to the compositions and methods relating to compounds of Formula IP. Of note are counterparts of Embodiments 1- 62 wherein "Formula 1" is replaced by "Formula IP" to the extent that these counterpart embodiments limit the definition of substituents on Formula IP. Also of note are counterparts of Embodiments B1-B53 wherein "Formula IP" is replaced by "Formula 1" to the extent that these counterpart embodiments limit the definition of substituents on Formula 1.
Combinations of Embodiments B1-B53 are illustrated by: Embodiment Cl. A compound of Formula IP wherein
Q1 is independently a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5a; Q2 is independently a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5b; Q3 is independently a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring, or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5; R1 is C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C7 cycloalkyl, C1-C7 haloalkyl, C2-C7 haloalkenyl, C4-Q0 alkylcycloalkyl or C4-Q0 cycloalkylalkyl; each R2, R3 and R4 is independently H, halogen, cyano, nitro, C1-C7 alkyl,
C2-C7 alkenyl, C7-C7 alkynyl, C3-C7 cycloalkyl, C1-C7 haloalkyl, C2-C7 haloalkenyl, C1-C7 alkoxy, C1-C7 haloalkoxy, C1-C7 alkylthio,
C1-C7 alkylsulfϊnyl, C1-C7 alkylsulfonyl, C1-C7 haloalkylthio, C1-C7 haloalkylsulfmyl, C1-C7 haloalkylsulfonyl, C1-C7 alkylamino or C2-C7 dialkylamino; and each R5a, R5^ and R5c is independently halogen, cyano, nitro, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C7 cycloalkyl, C1-C7 haloalkyl,
C2-C7 haloalkenyl, C1-C7 alkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C7 haloalkoxy, C1-C7 haloalkylthio, C1-C7 haloalkylsulfmyl, C1-C7 haloalkylsulfonyl, C1-C7 alkylamino, C2-C7 dialkylamino, C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl or C3-C1Q trialkylsilyl. Embodiment C2. A compound of Formula Cl wherein
J is Q2; X is CR2; Y is N; and Z is CR4. Embodiment C3. A compound of Embodiment C2 wherein each R2 and R4 is independently H, halogen, cyano, C1-C3 alkyl, C2-C3 alkenyl, C3 cycloalkyl or C1-C3 haloalkyl; and each R5a and R5^ is independently halogen, cyano, nitro, C1-C3 alkyl, C2-C3 alkenyl, C3 cycloalkyl, C1-C3 haloalkyl, C2-C3 haloalkenyl, C1-C3 alkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 haloalkoxy or
C1-C7 haloalkylthio. Embodiment C4. A compound of Embodiment C3 wherein
Q1 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R5a; Q2 is a phenyl ring optionally substituted with up to 3 substituents independently selected from R5^; each R2 and R4 is independently H, halogen or C1-C3 alkyl; and each R5a and R5b is independently halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl or C1-C3 alkoxy. Embodiment C5. A compound of Embodiment C4 wherein each R2 and R4 is independently H, Cl, Br, I or C1-C2 alkyl; and each R5a and R5b is independently halogen, CH3 , OCH3 or CF3.
Embodiment C7. A compound of Embodiment Cl wherein X is CQ3; Y is CR3;
R3 is H, Cl, Br or CH3; Z is N;
J is R1; and R1 is C1-C2 alkyl.
Specific embodiments include compounds of Formula IP selected from the group consisting of:
4-chloro-l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole; 4-chloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl-lH-imidazole; 2,4-dichloro- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)- lH-imidazole; and 2,4-dichloro- 1 -(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)- lH-imidazole. Also, specific embodiments include compounds of Formula IP selected from the group consisting of:
4-chloro-l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole; 4-chloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl-lH-imidazole; 2,4-dichloro- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)- lH-imidazole; 1 -(4-chlorophenyl)-2,4-dichloro-5-(2,4,6-trifluorophenyl)- lH-imidazole (or 2,4-dichloro- 1 -(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)- lH-imidazole);
1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)-2,4-dimethyl- lH-imidazole (or 1 -(4- chlorophenyl)-5-(2,6-difluorophenyl)-2,4-dimethyl)-lH-imidazole); 4-chloro-l-(4-chlorophenyl)-2-methyl-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-2,4-dimethyl-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-2,4-dichloro-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl-lH-imidazole; l-(4-chlorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazole; 4-chloro-l-(4-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH-imidazole; 4-chloro-l-(4-chloro-3-fluorophenyl)-2-methyl-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dimethyl-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chloro-3-fluorophenyl)-5-(2,6-difluorophenyl)-2,4-dimethyl-lH-imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,6-difluorophenyl)-lH-imidazole; l-(4-chloro-3-fluorophenyl)-5-(2,6-difluorophenyl)-2,4-dimethyl-lH-imidazole;
4-chloro-l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH- imidazole; l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl-lH- imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazole
(or 1 -(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl- IH- imidazole);
4-chloro-l-(3-fluorophenyl)-2-methyl-5-(2,4,6-trifluorophenyl)-lH-imidazole;
2,4-dichloro- 1 -(3-fluorophenyl)-5-(2,4,6-trifluorophenyl)- lH-imidazole;
1 -(3-fluorophenyl)-5-(2,4,6-trifluorophenyl)-2,4-dimethyl- lH-imidazole (or 1 -(3- fluorophenyl)-5-(2,4,6-trifluorophenyl)-2,4-dimethyl)-lH-imidazole);
4-chloro-l-(3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH-imidazole;
1 -(4-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl- lH-imidazole (or 1 -(4-
3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl-lH-imidazole); l-(3-fluorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazole; l-(3-fluorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazole; l-(3-fluorophenyl)-2,4-dimethyl-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazole;
4-chloro-l-(3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH-imidazole;
4-chloro-l-(4-chlorophenyl)-2-methyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-2,4-dimethyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; and l-(4-chlorophenyl)-2,4-dichloro-5-(2,3,6-trifluorophenyl)-lH-imidazole;
4-chloro-l-(3-fluorophenyl)-2-methyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(3-fluorophenyl)-2,4-dimethyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(3-fluorophenyl)-2,4-dichloro-5-(2,3,6-trifluorophenyl)-lH-imidazole;
4-chloro-5-(2-chloro-4-fluorophenyl)- 1 -(4-chlorophenyl)-2-methyl- lH-imidazole;
5-(2-chloro-4-fluorophenyl)- 1 -(4-chlorophenyl)-2,4-dimethyl- lH-imidazole; and
5-(2-chloro-4-fluorophenyl)-l-(4-chlorophenyl)-2,4-dichloro-lH-imidazole (or l-(2- chloro-4-fluorophenyl)-l-(4-chlorophenyl)-2,4-dichloro-lH-imidazol).
Of note are compounds of Formula 1 or Formula IP including geometric and stereoisomers, iV-oxides, and salts thereof (including but not limited to Embodiments 1-62, A1-A5, Bl-53 and C1-C6, above) wherein when Q1 is a phenyl ring which is not substituted by R5a at either ortho positions, then when X is N or CR2 and Q2 is a phenyl ring, the Q2 phenyl ring is substituted by at least one R5*5 at an ortho position.
This invention provides a fungicidal composition comprising a compound of Formula 1 or Formula IP (including all geometric and stereoisomers, iV-oxides, and salts thereof), and at least one other fungicide. Of note as embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above.
This invention provides a fungicidal composition comprising a fungicidally effective amount of a compound of Formula 1 or Formula IP (including all geometric and stereoisomers, iV-oxides, and salts thereof), and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Of note as embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above.
This invention provides a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula 1 or Formula IP (including all geometric and stereoisomers, iV-oxides, and salts thereof). Of note as embodiment of such methods are methods comprising applying a fungicidally effective amount of a compound corresponding to any of the compound embodiments describe above. Of particular note are embodiments where the compounds are applied as compositions of this invention.
One or more of the following methods and variations as described in Schemes 1-17 can be used to prepare the compounds of Formula 1 or Formula IP. The definitions of Q1, Q2, Q3, R1, R2, R3 and R4 in the compounds of Formulae 1-26 below are as defined above in the Summary of the Invention unless otherwise noted. Compounds of Formulae Ia-Ie are various subsets of Formula 1, and all substituents for Formulae Ia-Ie are as defined above for Formula 1 unless otherwise noted.
Compounds of Formula Ia (Formula 1 wherein J is Q2, X is CR2, Y is N and Z is CR4) can be prepared by halogenation or alkylation of compounds of Formula Ib (i.e. Formula 1 wherein J is Q2, X is CR2, R2 is H, Y is N and Z is CR4) as illustrated in Scheme 1. Typically halogenation can be achieved using a variety of halogenating reagents known in the art such as elemental halogen (e.g., CI2, Br2, I2), sulfuryl chloride, iodine monochloride or a JV-halosuccinimide (e.g., NBS, NCS, NIS) in an appropriate solvent such as Λ/,Λ/-dimethylformamide, carbon tetrachloride, acetonitrile, dichloromethane or acetic acid. Alkylation is achieved by reacting a compound of Formula Ib with a metalating agent, followed by an alkylating agent of formula R2-Lg (wherein Lg is a leaving group such as Cl, Br, I or a sulfonate, for example, /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate). Suitable metalating agents include, for example, as n-butyl lithium (n-BuLϊ), lithium diisopropylamide (LDA) or sodium hydride (NaH). As used herein, the terms "alkylation" and "alkylating agent" are not limited to R2 being an alkyl group, and include in addition to alkyl such groups as alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like. For reaction conditions see Almansa et al., Journal of Medicinal Chemistry 2003, 4(5(16), 3463-3475 and Katritzky et al., Heterocycles 1997, 44, 67-70. Also, the method of Scheme 1 is illustrated in Examples 5, 6 and 8. Scheme 1
Ib Ia
Compounds of Formula Ia can be subjected to various nucleophilic and metallation reactions to add substituents or modify existing substituents, and thus provide other functionalized compounds of Formula Ia. For example, compounds of Formula Ia wherein R2 and/or R4 are halogen can undergo nucleophilic displacements to provide compounds of Formula Ia wherein R2 and/or R4 are groups linked to the imidazole ring through an O, S or N atom (e.g., displacements with alkoxides, thiolates and amines). Typically these reactions are run in the presence of a suitable base (e.g., an sodium hydride, potassium t-butoxide, potassium carbonate or triethylamine) in a solvent such as alcohol, acetonitrile or Λ/,Λ/-dimethylformamide at temperatures ranging from room temperature to the reflux temperature of the solvent. General procedures for conducting nucleophilic displacements of halogens are known in the art and can be readily adapted to prepare compounds of the present invention. For procedures relevant to imidazoles see Grimmett et al., Australian Journal of Chemistry 1987, 40(8), 1399-1413.
Additionally, compounds of Formula Ia wherein R2 and/or R4 are iodo can be used to prepare the corresponding thiocyanate (-SCN) derivatives of Formula Ia. Typical conditions involve contacting the iodo compound of Formula Ia with a thiocyanating agent such as K[Cu(SCN)2], which is generated in situ from equimolar amounts of copper(I) thiocyanate and potassium thiocyanate. The reaction is typically carried out in a polar solvent such as Λ/,Λ/-dimethylformamide, dimethylacetamide, 1,4-dioxane or dimethylsulfoxide at a temperature between about room temperature and the reflux temperature of the solvent. The reaction can also be carried out at higher temperatures using a microwave reactor. For a reference see, for example, Suzuki et al., Synthetic Communications 1996, 2(5(18), 3413- 3419.
Also, compounds of Formula Ia wherein R2 and/or R4 are bromo or iodo can be cross-coupled with compounds of formulae R2-Met or R4-Met (wherein Met is Sn, Zn, B(OH)2, Mg, Li, Cu or other suitable counterions) in the presence of a palladium or nickel catalyst to produce compounds of Formula Ia wherein R2 and/or R4 are cyano, alkyl, alkenyl, haloalkenyl, alkynyl, and the like. Preferred catalysts include but are not limited to Pd(PPh3)4, PdCl2(PPh3)2, PdCl2(diphenylphosphinoferrocene), NiCl2(PPh3)2 and tetrakis(tri-2-furylphosphino)palladium. The exact conditions for each reaction will depend upon the catalyst used and the counterions in the compound of formulae R2-Met or R4-Met. The presence of a base (such as an alkali carbonate, tertiary amine or alkali fluoride) is necessary for reactions involving compounds of formulae R2-Met or R4-Met where Met is B(OH)2. Examples 13, 16, 17, 18, 19 and 31 illustrate various cross-coupling reactions for the preparation of certain compounds of Formula Ia.
As shown in Scheme 2, compounds of Formula Ia can alternatively be prepared by halogenation of a compound of Formula 2 preferentially at the 4-position of the imidazole ring to provide a compound of Formula Ic (Formula 1 wherein J is Q2, X is CR2, Y is N, Z is CR4 and R4 is H) wherein R2 is halogen, which can then be treated with a second equivalent of the same or different halogenating reagent to provide a compound of Formula Ia wherein R2 and R4 are halogen. For an example illustrating the method of Scheme 2 for the preparation of a compound of Formula Ic see Step C of Examples 1 and 34. Also, for an example illustrating the method of Scheme 2 for the preparation of a compound of Formula Ia wherein R2 is chloro and R4 is bromo see Example 35. Alternatively, compounds of Formula 2 can be treated with 2 equivalents of a halogenating reagent to provide a compound of Formula Ia directly wherein R2 and R4 are both the same halogen. For an example illustrating the method of preparing a compound of Formula Ia wherein R2 and R4 are both the same halogen see Example 2 and Step C of Example 3.
Alternatively as also shown in Scheme 2, compounds of Formula Ia wherein R4 is halogen, alkyl, alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like can be prepared from compounds of Formula Ic by metallation with a reagent such as n-butyllithium (n-BuLi), lithium diisopropylamide (LDA) or sodium hydride (NaH) in a solvent such as tetrahydrofuran, dioxane or toluene at temperatures ranging from about 0 0C to room temperature. The anion is then contacted with an electrophile resulting in the introduction of an R4 group onto Formula Ic, thus providing a compound of Formula Ia.
Scheme 2
Figure imgf000048_0001
Ic halogenation reagent / or
1. metalating agent
1. electrophile (e.g., halogenating agent or R -Lg)
Figure imgf000048_0002
Ia wherein R is halogen
Synthesis of compounds of Formula Ib can be achieved as outlined in Scheme 3. In the first step a compound of Formula 3 is JV-arylated with halides of formula Q2X1 wherein X1 is I, Cl, Br or F. There are a number of conditions published in the chemistry literature which can be used for introduction of a substituted aryl or a heteroaryl group onto Formula 3, including copper-catalyzed conditions involving the use of a suitable copper source (e.g., copper(I) iodide or copper(I) triflate) and a metal carbonate base (e.g., potassium or cesium carbonate) in a suitable solvent such as xylenes, dioxane or acetonitrile (see Buchwald et al., Tetrahedron Letters 1999, 40, 2657-2660 and Jiang et al., Journal of Organic Chemistry 2007, 72, 8943-8946). The method of Scheme 3 for the preparation of a compound of Formula 4 is also illustrated in Step A of Example 7.
In a subsequent step, compounds of Formula 4 can be converted directly to Formula Ib by reaction with a halide of formula Q1X1 in the presence of palladium(II) acetate and a triarylphosphine ligand and cesium fluoride in a solvent such as dioxane, tetrahydrofuran or acetonitrile at the reflux temperature of the solvent. For a representative reference see Bellina et al., Journal of Organic Chemistry 2005, 70, 3997-4005. Also, Step B of Example 7 illustrates the preparation of a compound of Formula Ib using the method of Scheme 3. Alternatively, lithiation of a compound of Formula 4 with n-butyllithium (n-BuLi) or lithium diisopropylamide (LDA), followed by treatment of the anion with trialkylorganostannyl chlorides or boronic acids (or esters) provides compounds of Formula 5. Treatment of compounds Formula 5 with a halide of formula Q1X1 using well-known transition metal-catalyzed cross coupling reaction conditions provides Formula Ib compounds. Typically the reaction is run in the present of a palladium catalyst. A wide variety of palladium-containing compounds and complexes are useful as catalysts in the method of Scheme 3, including PdCl2(PPh3 )2 (bis(triphenylphosphine)palladium (II) dichloride), Pd(PPh3)4 (tetrakis(triphenylphosphine)-palladium(O)) and Pd2(dba)3. For relevant references see, for example, Ragan et al, Organic Process Research & Development 2003, 7(5), 675-683; and Gaare et al., Acta Chemica Scandinavica 1993, 47, 57-62.
Scheme 3
F
Figure imgf000049_0001
wherein L is (alkyl)3Sn or B(OH)2
Compounds of Formula Ib can also be prepared as shown in Scheme 4. In this method a compound Formula 6 is first metallated with a metalating agent such as n-butyl lithium (n-BuLi), lithium diisopropylamide (LDA) or sodium hydride (NaH) in a solvent such as tetrahydrofuran, dioxane or toluene at temperatures ranging from about 0 0C to room temperature. The anion is then contacted with an electrophile resulting in the introduction of an R4 group onto Formula 6, thus providing a compound of Formula Ib. For halogenation, the electrophile can be a halogen derivative such as JV-chlorosuccinimide (NCS),
Λ/-bromosuccinimide (NBS), TV-iodosuccinimide (NIS), hexachloroethane or
1,2-dibromotetrachloroethane. For alkylation, the electrophile can be an alkylating agent of the formula R4-Lg (wherein Lg is a leaving group such as Cl, Br, I or a sulfonate, for example, /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate) where R4 is alkyl, alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like. As referred to herein, the terms "alkylation" and "alkylating agent" are not limited to R4 being an alkyl group. For related reference see Almansa et al., Journal of Medicinal Chemistry 2003, 46, 3463-3475. Also, Example 4 illustrates the method of Scheme 4 using LDA and iodomethane.
Scheme 4
Figure imgf000050_0001
6 Ib Compounds of Formula 6 are known and can be prepared by one of several methods disclosed herein. For example, using the method disclosed in Scheme 3, starting with a compound of Formula 3 wherein R4 is H provides compounds of Formula 6. Alternatively, compounds of Formula 6 can be prepared by the method of Scheme 6 described below using a compound of Formula 10 or 11 wherein R2 is H (i.e. when R2 is H, Formula 10 is /?-toluenesulfonylmethyl isocyanide and Formula 11 is benzotriazol-1-yl-methyl isocyanide). For synthesis of a compound of Formula 6 using /?-toluenesulfonylmethyl isocyanide see Step B of Examples 1 and 3.
In another method illustrated in Scheme 5, compounds of Formula Ib can be prepared by reacting JV-chloroamidines of Formula 7 with enamines of Formula 8. In this method cyclization proceeds through the intermediacy of an in szYw-generated 4-morpholino-4,5- dihydroimidazole which undergoes elimination of the morpholino group to provide the compounds of Formula Ib. Typically the reaction is run in the presence of a base such as pyridine, 4-(dimethylamino)pyridine or a trialkylamine and in a suitable solvent, such as dichloromethane, trichloromethane, carbon tetrachloride or toluene, at temperatures ranging from about 0 0C to the reflux temperature of the solvent. For a representative reference see Pocar et al., Tetrahedron Letters 1976, 21, 1839-1842. One skilled in the art will recognize that imidazole rings of Formula Ib can also be prepared by numerous other methods described in the chemistry literature. For example, the general method described by Wiglenda et al., Journal of Medicinal Chemistry 2007, 50(1), 1475-1484 can be used to prepare compounds of Formula Ib; the method can also be readily adapted to prepare Formula Ib compounds wherein each Q1 and/or Q2 is an optionally substituted benzyl group. Scheme 5
Figure imgf000051_0001
Ib
Compounds of Formula 7 can be easily synthesized from amidines and JV-chlorosuccinimide according to the procedure given by Pocar et al., Tetrahedron Letters 1976, 21, 1839-1842. Enamines of Formula 8 can be prepared by known methods; for example, see van der Gen et al., Tetrahedron Letters 1979, 26, 2433-2436.
As shown in Scheme 6, compounds of Formula Ic can be prepared by reacting an imine of Formula 9 with a substituted /?-toluenesulfonylmethyl isocyanide of Formula 10 or a substituted benzotriazol-1-ylmethyl isocyanide of Formula 11 in the presence of a suitable base such as potassium carbonate, potassium tert-butoxide, sodium hydroxide, sodium hydride, te/t-butylamine or l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in an appropriate solvent such as methanol, dioxane, tetrahydrofuran, dimethylsulfoxide,
Λ/,Λ/-dimethylformamide or dimethoxy ethane, at temperatures ranging from about 0 to
150 0C. For reaction conditions see Almansa et al., Journal of Medicinal Chemistry 2003, 46(16), 3463-3475 and Katritzky et al., Heterocycles 1997, 44, 67-70. The method of
Scheme 6 is also illustrated in Step B of Examples 9, 34 and 37.
Figure imgf000052_0001
11
Imines of Formula 9 can be readily prepared by contacting an amine of Formula Q2NH2 with an aldehyde of formula Q1CHO under dehydrative conditions such as heating in toluene or xylenes with use of a Dean-Stark trap to remove water formed in the reaction. In some cases, an acid catalyst such as /?-toluenesulfonic acid can be added to the reaction mixture to promote elimination of water. For representative procedures see Almansa et al., Journal of Medicinal Chemistry 2003, 46(16), 3463-3475. Also, Step A of Examples 1, 3, 9, 34 and 37 illustrate the preparation of a compound of Formula 9. Compounds of Formula 10 can be prepared from the unsubstituted
/?-toluenesulfonylmethyl isocyanide under phase-transfer conditions using methods reported in the chemical literature; see, for example, Leusen et al., Tetrahedron Letters 1975, 40, 3487-3488.
The substituted benzotriazol-1-ylmethyl isocyanides of Formula 11 can be prepared by contacting benzotriazol-1-yl-methyl isocyanide with a compound of formula R2X1 (wherein X1 is halogen) in the presence of a base such as potassium carbonate, sodium hydride or potassium tert-butoxide. For typical reaction conditions see Katritzky et al., Heterocycles 1997, 44, 67-70. One skilled in the art will recognize other methods for preparing compounds of Formula 11, for example, the method described by Katritzky et al., Journal of the Chemical Society, Perkin Transactions 1 , 1990, (7), 1847- 1851.
Certain compounds of Formula Ic wherein R2 is halogen can be prepared as shown in Scheme 7. In this method an aminonitrile of Formula 12 is combined with a methanaminium salt of Formula 13 to provide a compound of Formula Ic according to the general method taught by Pawar et al., Tetrahedron Letters 2006, 47, 5451-5453. The reaction is run in a suitable solvent such as dichloromethane or toluene at temperatures ranging from about 0 0C to the reflux temperature of the solvent. The method of Scheme 7 is illustrated in Step B of Examples Hand 14.
Halogenation at the 2-position of the imidazole ring of Formula Ic can be achieved using methods analogous to those already described for Scheme 2 to provide compounds of Formula Ia wherein R2 is halogen. Examples 12, 15, 30, 35 and 38 illustrate this halogenation method.
Scheme 7
Figure imgf000053_0001
wherein R is halogen
Aminonitriles of Formula 12 are readily available from amines of formula Q2NH2, aldehydes of formula Q1CHO and a cyanide source by means of the Strecker reaction. A variety of solvents and cyanide sources can be employed. The presence of a Lewis acid such as indium(III) chloride can be advantageous. For typical conditions, see, for example, Ranu et al, Tetrahedron, 2002, 58, 2529-2532. This reaction has been the subject of a number of reviews. For conditions and variations of this reaction see the following references and references cited therein: D. T. Mowry, Chemical Reviews 1948, 42, 236, H. Groeger, Chemical Reviews 2003, 103, 2795-2827, and M. North in Comprehensive Organic Functional Group Transformations A. R. Katritsky, O. Meth-Cohn and C. W. Rees Editors., Volume 3, 615-617; Pergamon, Oxford, 1995. Also the preparation of a compound of Formula 12 is illustrated in Step A of Examples 11 and 14. For less reactive amines of formula Q2NH2, such as aryl amines containing ortho electron withdrawing groups, the use of trimethylsilylcyanide in combination with a catalyst such a guanidine hydrochloride can be advantageous. For a reference see, for example, Heydari et al., Journal of Molecular Catalysis A: Chemical 2007 , 277(1-2), 142-144.
Methanaminium salts of Formula 13 are commercially available, for example, chloromethylenedimethyliminium chloride (i.e. R2 and X1 are Cl) can be obtained from commercial sources. Compounds of Formula 13 can also be synthesized by methods documented in the chemistry literature.
Other functionalized compounds of Formula Ia can be prepared as shown in Schemes 8 and 9. In Scheme 8, compounds of Formula Ic are used to provide the corresponding 2-imidazolecarboxaldehyde derivatives of Formula IaI ^ 6 Formula Ia wherein R4 is -CHO). In this reaction the imidazole ring is first lithiated at the 2-position using a lithium base such as lithium diisopropylamide (LDA), followed by treatment of the anion with Λ/,Λ/-dimethylformamide (DMF) provides the 2-imidazolecarboxaldehyde derivative. The method of Scheme 8 is illustrated in Example 20.
Scheme 8
Figure imgf000054_0001
Ic Ia1
As shown in Scheme 9, the 2-imidazolecarboxaldehyde of Formula Ia1 can be reduced with sodium borohydride in methanol to provide the corresponding compound of Formula Ia2 (i.e. Formula Ia wherein R4 is 2-hydroxymethyl). For reaction conditions see Quan et al., Journal of Medicinal Chemistry 2005, 48(6), 1729-1744. Also for the preparation of a 2-hydroxymethyl derivative using the method of Scheme 9 see Example 21. Treatment of the 2-hydroxymethyl compound of Formula Ia2 with diethylaminosulfur trifluoride (DAST) results in the 2-fluoromethyl derivative of Formula Ia3 (i.e. Formula Ia wherein R4 is -CH2F). For reaction conditions see C. J. Wang, Organic Reactions 2005, Vol. 34 (Wiley, New York, 1951) Chapter 2, pp. 319-321. Also the method of Scheme 9 for the preparation of a 2-fluoromethyl derivative is illustrated in Example 22. Other 2-halomethyl analogs of Formula Ia3 can be prepared using methods described in the chemistry literature. For example, 2-bromomethyl analogs of Formula Ia3 can be prepared by treating 2-hydroxymethyl compounds of Formula Ia2 with hydrobromic acid in a solvent such as glacial acetic acid using the method described by Beukers et al., Journal of Medicinal Chemistry 2004, 47(15), 3707-3709.
Also as shown in Scheme 9, the 2-imidazolecarboxaldehyde can be treated with hydroxylamine hydrochloride to provide the oxime of Formula Ia4 (i.e. Formula Ia wherein R4 is oxime functionality). For reaction conditions see Oresmaa et al., Journal of Medicinal Chemistry 2005, 48(\ 3), 4231-4236, and Example 23. Alternatively,
2-imidazolecarboxaldehyde compounds of Formula lal can be treated with a hydroxylamine salt of formula F^NOR^ΗCl to provide compounds of Formula 1 wherein R4 is -CH=NOR11. For a relevant reference, see PCT Patent Publication WO 2006/086634. Scheme 9
Figure imgf000055_0001
Figure imgf000055_0002
Ia4
Schemes 5 through 7 are representative of just a few methods of preparing imidazole rings of the present invention. One skilled in the art will recognize that imidazole rings of Formula Ia can also be prepared by numerous other methods described in the chemistry literature. For leading references on imidazole synthesis see Grimmett in Imidazole and Benzimidazole Synthesis, Academic Press, California; and Grimmett, Science of Synthesis 2002, 12, 325-528.
Compounds of Formula Id (i.e. Formula 1 wherein J is R1, X is CQ3, Y is CR3 and Z is N) can be prepared as shown in Scheme 10 by cyclization of a 1,3-dicarbonyl compound of Formula 14 with an appropriately substituted hydrazine of formula NH2NHRI in a suitable solvent such as ethanol, methanol, acetonitrile, glacial acetic acid, or mixtures thereof. The reaction is conducted at a temperature between about room temperature to the reflux temperature of the solvent and optionally in the presence of a base such as a metal carbonate, acetate or alkoxide. Two regioisomers can result from these types of reactions; however the desired regioisomer can be predominately formed by adjusting reaction conditions (e.g., solvent choice). For a general reference see, for example, Sliskovic et al., Journal of Medical Chemistry 1990, 33, 31-38 and Singh et al., Journal of Heterocyclic Chemistry 1989, 26, 733-738. Scheme 10
Figure imgf000056_0001
14 Id
Alternatively, compounds of Formula Id can be prepared as outlined in Scheme 11. In this method compounds of Formula 15 are first halogenated analogous to the method described in Scheme 2 to provide the compounds of Formula 16, which can then be coupled with a boronic acid of formula Q3B(OH)2 using well-known Suzuki palladium-catalyzed cross coupling reaction conditions. Many catalysts are useful for the Suzuki reaction; particularly useful catalysts include tetrakis(triphenylphosphine)palladium(0) and [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II). Solvents such as tetrahydrofuran, acetonitrile, diethyl ether and dioxane are suitable. Many boronic acids of formula Q3B(OH)2 are commercially available and others can be prepared by known methods. For a reference see, for example, Suzuki et al, Chemical Review 1995, 95, 2457-2483. Compounds of Formula Id wherein Q3 is a //-linked heteroaromatic ring can be prepared via a palladium-catalyzed cross-coupling reaction using compounds of formula Q3H. For leading references see, for example, Buchwald et al., Accounts of Chemical Research, 1998, 57(12), 805-818 and Hartwig, Angew. Chem. Int. Ed., 1998, 37, 2046-2067. Also, Example 40, Steps B-C illustrate the method of Scheme 11.
Scheme 11
Figure imgf000056_0002
15 16 Id wherein X is Br or I Compounds of Formula 15 can be prepared by the method of Scheme 10 using a hydrazine of formula NH2NHR1 and a dione of Formula 14 where Q3 is replaced by H. For a reference see Quan et al., Journal of Medicinal Chemistry 2005, 48(6), 1729-1744. For a specific example see Step A of Example 40. In another method, as shown in Scheme 12, compounds of Formula Id can be prepared by introduction of the R1 substituent via alkylation of the pyrazole ring with an alkylating agent Ri-Lg wherein Lg is a leaving group such as Cl, Br, I or a sulfonate such as /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate. As referred to herein, the terms "alkylation" and "alkylating agent" are not limited to R1 being an alkyl group and include in addition to alkyl such groups as alkylthio, haloalkyl, alkenyl, haloalkenyl, alkynyl, and the like. Alkylation of pyrazoles using potassium carbonate in N,N-dimethylformamide or acetone are described by Kitazaki et al, Chem. Pharm. Bull. 2000, 48(12), 1935-1946 and Jeon et al., Journal of Fluorine Chemistry 2007, 128, 1191-1197. One skilled in the art recognizes that a variety of bases and solvents can be used for alkylation of pyrazoles; for example, Alabaster et al., Journal of Med. Chemistry 1989, 32, 575-583 discloses use of sodium carbonate in N,Λ/-dimethylformamide, Wang et al., Organic Letters 2000, 2(20), 3107-3109 discloses use of potassium tert-butoxidc in methyl sulfoxide, and European Patent Application Publication EP-1081146-A1 describes the use of sodium or potassium hydroxide in methyl sulfoxide and in the presence of a phase transfer catalyst. For an example illustrating the method of Scheme 12 using sodium hydride in N,Λ/-dimethylformamide see Step E of Example 39. One skilled in the art also recognizes that a variety of alternative synthetic methods are applicable for preparing compounds of Formula Id including, for example, condensation with aryl iodides in the presence of copper(I) iodide and trans-cyclohexanediamine as reported by Buchwald et al., J. Am. Chem. Soc. 2001, 123, 7727-7729, and condensation with aryl boronic acids in the presence of copper(II) acetate and pyridine as reported by Lam et al., Tetrahedron Letters 1998, 39, 2941-2944. In some cases, depending on the reaction conditions, two regioisomers can be formed; the regioisomers can be separated by methods known to those skilled in the art, including chromatography.
Scheme 12
Figure imgf000057_0001
^ _ wherein R is halogen or alkyl
1 7 Id
Starting compounds of Formula 17 wherein R3 is halogen or alkyl can be prepared from the corresponding compounds wherein R3 is H by halogenation or alkylation analogous to the method described in Scheme 1. For reaction conditions see, in addition to the references cited in Scheme 1, U.S. patent application publication 2007/054896 and Toto et al., Synthetic Communications 2008, 38(5), 674-683. For a specific example, see Step D of Example 39. Preparation of compounds of Formula 17 where in R3 is H (i.e. the precursor to Formula 17) can be accomplished by condensing compounds of Formula 18 with hydrazine as shown in Scheme 13. The reaction can be run in a variety of solvents, but typically optimal yields are obtained when the reaction is run in ethanol at a temperature between about room temperature and the reflux temperature of the solvent. General procedures for this type of reaction are well documented in the chemical literature; for example, see Maya et al, Bioorganic & Medicinal Chemistry 2005, 13(6), 297-2107; and Domagala et al., Journal of Heterocyclic Chemistry 1989, 26, 1147-1158. The method of Scheme 13 is also illustrated in Step C of Example 39. Scheme 13
Figure imgf000058_0001
18 17 wherein R is H
Alternatively, alkylhydrazines (i.e. R1NFINF^) can be used in place of hydrazine in the method of Scheme 13 to provide compounds of Formula 17 wherein R1 is other than hydrogen (e.g., alkyl). Typically these reactions result in mixtures of 1- and 2-substituted pyrazole regioisomers which can be separated using chromatography.
Compounds of Formula 18 can be prepared from ketones of Formula 19 and Λ/,Λ/-dimethylformamide dimethyl acetal using the method described by Maya et al., Bioorganic & Medicinal Chemistry 2005, 13(6), 297-2107. The reaction is typically conducted in a solvent such as benzene, toluene or xylenes at a temperature between about room temperature and the reflux temperature of the solvent. The method of Scheme 14 is illustrated in Step B of Example 39.
Scheme 14
Figure imgf000058_0002
19
18
Ketones of Formula 19 can be prepared by reaction of acid chlorides of Formula 20 with the desired aromatic species of formula Q1 -H under Friedel-Crafts condensation reaction conditions. Friedel-Crafts reactions are documented in a variety of published references including Lutjens et al., Journal of Medicinal Chemistry 2003, 46(10), 1870- 1877; PCT Patent Publication WO 2005/037758; and J. March, Advanced Organic Chemistry, McGraw-Hill, New York, p 490 and references cited within. The method of Scheme 15 is also illustrated in Step A of Example 39.
Scheme 15
Figure imgf000059_0001
19
In another method, compounds of Formula Id wherein R3 is halogen or cyano can be synthesized as shown in Scheme 16. In the first step, cyclization of 2-cyanoketones of
10 Formula 23 with hydrazines of formula NH2NHR1 in a suitable solvent such as ethanol, methanol or glacial acetic acid gives 3-aminopyrazoles of Formula 24. Cyclization reactions of this type are documented in the chemical literature; see, for example, Compton et al., Journal of Medical Chemistry 2004, 47, 5872-5893. Typically these reactions result in mixtures of 1- and 2-substituted pyrazole regioisomers which can be separated using
15 chromatography. Using Sandmeyer reaction conditions, amines of Formula 24 can be converted to diazonium salts and then reacted with a copper salt (e.g., copper(I) halide, copper(II) halide or copper(I) cyanide) in the presence of an acid to provide compounds of Formula Id. The diazonium salt formed from the amine of Formula 24 is generated under standard conditions, for example, strong acid (e.g., hydrochloric acid or hydrobromic acid)
20 and sodium nitrite or using non-aqueous conditions. For a review of the Sandmeyer reaction see Hodgson, Chemical Reviews 1947, 40(1), 251-211. Also, copper chloride, tert-bvΛy\ nitrite and acetonitrile can be used according to the general method disclosed by South, Journal of Heterocyclic Chemistry 1991, 28, 1003-1011.
Scheme 16
Figure imgf000059_0002
ry r wherein R is halogen or CN Compounds of Formula Ie (i.e. Formula 1 wherein J is Q2' X is CR2, Y is N and Z is N) can be prepared by cycloaddition of alkynes to azides as illustrated in Scheme 17. In this method bromomagnesium or lithium acetylides are first generated by reaction of an alkyne of Formula 25 with a Grignard reagent or an alkyl lithium base, followed by reaction with an azide of Formula 26. The cyclization reaction proceeds through the intermediacy of an in szYw-generated 4-metallotriazole which when treated with an electrophile of formula R2-Lg (wherein Lg is a leaving group such as Cl, Br, I or a sulfonate, for example, /?-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate) provides the corresponding compound of Formula Ie. Typically the reaction is run in an aprotic solvent, such as tetrahydrofuran, at temperature between about 0 0C to the reflux temperature of the solvent. For a representative reference see Krasinski et al., Organic Letters 2004, 6(8), 1237-1240. The method of Scheme 17 is illustrated in Step B of Example 42.
Scheme 17
Figure imgf000060_0001
wherein R is a wherein M is MgX or Li lower alkyl group Compounds of Formula 1 and the intermediates described above can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation and reduction reactions to add or modify substituents for formation of further compounds of Formula 1. Compounds wherein R2, R3, R4, R5a, R5^ or R5c is halogen (preferably bromide or iodide) are particularly useful intermediates for transition metal-catalyzed cross-coupling reactions to prepare compounds of Formula 1. These types of reactions are well documented in the literature; see, for example, Tsuji in Transition Metal Reagents and Catalysts: Innovations in Organic Synthesis, John Wiley and Sons, Chichester, 2002; Tsuji in Palladium in Organic Synthesis, Springer, 2005; and Miyaura and Buchwald in Cross-Coupling Reactions: A Practical Guide, Springer, 2002; and references cited therein. One skilled in the art will recognize that for some compounds of Formula 1, the R5a,
R5^ and R5c substituents attached to the rings and ring systems of Q1, Q2 and Q3 may be more conveniently incorporated after forming the central azole ring with the rings or ring systems of Q1, Q2 and Q3 attached. In particular, when R5a, R5^ and/or R5c is halogen or another suitable leaving group, the leaving group can be replaced using various electrophilic, nucleophilic and organometallic reactions known in the art to introduce other functional groups as R5a, R5*5 and R5c. Example 29 demonstrates the preparation of a compound of Formula Ia wherein R5a is cyano (-CN) starting from the corresponding compound of Formula Ia wherein R5a is bromo. Example 43 illustrates the preparation of a compound of Formula Ia wherein R5^ is thiocyanate (-SCN) starting from the corresponding compound of Formula Ia wherein R5^ is iodo. Furthermore, compounds of Formula 1 wherein a ring or ring system of Q1, Q2 or Q3 is substituted with an R5a, R5^ or R5c substituent which is -U-V-T (as defined in the Summary of the Invention) can be prepared from the corresponding compounds of Formula 1 wherein R5a, R5^ or R5c is a halogen or other suitable leaving group, such as by the general method described in PCT Patent Publication WO 2007/149448 (see Scheme 15 therein). This reference also describes other general methods for forming an R5a, R5^ or R5c substituent as -U-V-T (see Schemes 16-19 therein). Present Examples 32 through 33 demonstrate the preparation of a compound of Formula Ia wherein R5a is -U-V-T (i.e. -0(CH2^NHCH3) starting from the corresponding compound of Formula Ia wherein R5a is methoxy. It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula 1 may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formula 1. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula 1.
Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Steps in the following Examples illustrate a procedure for each step in an overall synthetic transformation, and the starting material for each step may not have necessarily been prepared by a particular preparative run whose procedure is described in other Examples or Steps. In the following Examples HPLC analyses were obtained on an Alltech Altima C18 analytical column with UV detection. The solvent system was solvent A: water with 0.05% trifluoroacetic acid by volume/volume, and solvent B: acetonitrile with 0.05% trifluoroacetic acid by volume/volume (gradient started at 0 minutes with 90% solvent A and 10% solvent B and increased solvent B to 90% over 20 minutes, flow rate was 1 mL/minute). Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. The mass spectra value given in the following Examples is the molecular weight of the highest isotopic abundance parent ion (M+ 1) formed by addition of H+ (molecular weight of 1) to the molecule, observed by mass spectrometry using electrospray ionization (ESI). 1H NMR spectra are reported in ppm downfield from tetramethylsilane; "s" means singlet, "d" means doublet, "m" means multiplet.
EXAMPLE 1 Preparation of 4-chloro-l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole (Compound 1)
Step A: Preparation of (E)-4-chloro-Λ/-[(2,4,6-trifluorophenyl)methylene]benzene
To a mixture of 2,4,6-trifluorobenzaldehyde (3.0 g, 18.7 mmol) in toluene (10O mL) was added 4-chloroaniline (2.39 g, 18.7 mmol). The reaction mixture was heated at reflux with the use of a Dean-Stark trap for the azeotropic removal of water. After 16 h the reaction mixture was cooled to room temperature and concentrated under reduced pressure.
The resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes
(1 : 9) as eluant to provide the title compound as a pale-yellow solid (4.20 g).
1H NMR (CDCl3): δ 8.55 (s, IH), 7.37-7.34 (m, 2H), 7.17-7.13 (m, 2H), 6.83-6.77 (m, 2H). ESI MS m/z 270 (M+ 1).
Step B Preparation of l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole
To a mixture of (E)-4-chloro-N-[(2,4,6-trifluorophenyl)methylene]benzene (i.e. the product of Step A) (4.2O g, 15.6 mmol) in methanol and 1 ,2-dimethoxyethane (2 : 1,
152 mL) was added /?-toluenesulfonylmethyl isocyanide (4.57 g, 23.4 mmol) and potassium carbonate (4.30 g, 31.2 mmol). The reaction mixture was heated at 85 0C for 4 h, cooled, and then concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate (200 mL), washed with water (75 mL) and saturated aqueous sodium chloride
(75 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound as a pale yellow solid (1.30 g, 98.9 area % purity by ΗPLC) melting at 170-172 0C.
1H NMR (DMSO-J6): δ 7.29 (s, IH), 7.11-7.07 (m, 2H), 6.68-6.63 (m, 2H).
MS m/z 309 (M+l).
Step C Preparation of 4-chloro-l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH- imidazole
To a mixture of l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole (i.e. the product of Step B) (0.100 g, 0.32 mmol) in chloroform (2 mL) was added JV-chlorosuccinimide (0.046 g, 0.34 mmol). The reaction mixture was heated at reflux for 16 h and then cooled to room temperature. The reaction mixture was diluted with chloroform (100 mL), washed with water (55 mL) and saturated aqueous sodium chloride (55 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound, a compound of the present invention, as an off- white solid (0.075 g, 98.9 area % purity by HPLC) melting at 102-104 0C. 1H NMR (CDCl3): δ 7.68 (s, IH), 7.37-7.33 (m, 2H), 7.11-7.07 (m, 2H), 6.74-6.65 (m, 2H). ESI MS m/z 343 (M+ 1). EXAMPLE 2
Preparation of 2,4-dichloro-l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole
(Compound 6) To a mixture of l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole (i.e. the product of Step B of Example 1) (0.280 g, 0.90 mmol) in chloroform (10 mL) was added JV-chlorosuccinimide (0.420 g, 3.14 mmol). The reaction mixture was heated at reflux for
16 h and then cooled to room temperature. The reaction mixture was diluted with chloroform (100 mL), washed with water (55 mL) and saturated aqueous sodium chloride solution (55 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound, a compound of the present invention, as a pale-yellow solid (0.23 g, 96.7 area % purity by ΗPLC) melting at 112-
119 0C.
1H NMR (CDCl3): δ 7.40-7.35 (m, 2H), 7.14-7.10 (m, 2H), 6.70-6.61 (m, 2H).
ESI MS m/z 377 (M+l). EXAMPLE 3
Preparation of 2,4-dichloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole
(Compound 3) Step A: Preparation of (E)-4-chloro-Λ/-[(2,6-difluorophenyl)methylene]benzene
To a mixture of 2,6-difluorobenzaldehyde (4.0 g, 18.7 mmol) in toluene (100 mL) was added 4-chloroaniline (3.60 g, 28.0 mmol). The reaction mixture was heated at reflux with the use of a Dean-Stark trap for azeotropic removal of water. After 16 h the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes (0.5 : 9.5) as eluant to provide the title compound as a pale -yellow solid (6.20 g). 1H NMR (CDCl3): δ 8.64 (s, IH), 7.44-7.33 (m, 3H), 7.19-7.14 (m, 2H), 7.04-6.96 (m, 2H). Step B Preparation of l-(4-chlorophenyl)-5-(2, 6-difluorophenyl)-lH-imidazole
To a mixture of (E)-4-chloro-Λ/-[(2,6-difluorophenyl)methylene]benzene (i.e. the product of Step A) (4.0 g, 16.0 mmol) in methanol and 1 ,2-dimethoxyethane (7 : 3, 160 mL) was added /?-toluenesulfonylmethyl isocyanide (4.67 g, 24.0 mmol) and potassium carbonate (4.65 g, 24.0 mmol). The reaction mixture was heated at 85 0C for 4 h, cooled, and then concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate (200 mL), washed with water (75 mL) and saturated aqueous sodium chloride solution (75 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography using ethyl acetate-hexanes (3 : 7) as eluant to provide the title compound as a pale-yellow solid (1.40 g, 98.9 area % purity by ΗPLC) melting at 170-172 0C. 1H NMR (CDCl3): δ 7.79 (d, J = 0.9 Hz, IH), 7.34-7.29 (m, 4H), 7.12-7.08 (m, 2H), 6.91-
6.83 (m, 2H). ESI MS m/z 291 (M+ 1). Step C Preparation of 2,4-dichloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH- imidazole
To a mixture of l-(4-chlorophenyl)-5-(2,6-trifluorophenyl)-lH-imidazole (i.e. the product of Step B) (0.60 g, 2.06 mmol) in chloroform (24 mL) was added JV-chlorosuccinimide (0.69 g, 5.17 mmol). The reaction mixture was heated at reflux for 16 h and then cooled to room temperature. The reaction mixture was diluted with chloroform (40 mL), washed with water (30 mL) and saturated aqueous sodium chloride solution (30 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound, a compound of the present invention, as an off-white solid (0.50 g, 97.9 area % purity by ΗPLC) melting at 123-125 0C. 1H NMR (CDCl3): δ 7.40-7.30 (m, 3H), 7.16-7.10 (m, 2H), 6.90-6.84 (m, 2H). ESI MS m/z 360 (M+l).
EXAMPLE 4 Preparation of l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl-lH-imidazole To a stirred mixture of l-(4-chlorophenyl)-5-(2,6-trifluorophenyl)-lH-imidazole (i.e. the product of Step B of Example 3) (1.0Og, 3.44 mmol) in tetrahydrofuran (34 mL) at -50 0C was added dropwise a solution of lithium diisopropylamide (1.0 M in tetrahydrofuran, 2.60 mL, 5.10 mmol). The reaction mixture was stirred at -50 0C for 1.5 h, and then a solution of iodomethane (1.47 g, 10.3 mmol) in tetrahydrofuran (16 mL) was added. The reaction mixture was slowly warmed to room temperature, stirred for 4 h, and then concentrated under reduced pressure. The resulting residue was diluted with dichloromethane (50 mL), washed with water (20 mL) and saturated aqueous sodium chloride solution (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate -hexanes (1 : 4) as eluant to provide the title compound, a compound of the present invention, as a pale-yellow solid (0.74 g). 1H NMR (CDCl3): δ 7.24-7.17 (m, IH), 7.14 (s, IH), 7.12-7.06 (m, 2H), 6.85-6.78 (m, 2H),
2.33 (s, 3H). ESI MS m/z 305 (M+l).
EXAMPLE 5 Preparation of 4-chloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl-lH-imidazole (Compound 2)
To a stirred mixture of l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl-lH- imidazole (i.e. the product of Example 4) (0.740 g, 2.40 mmol) in chloroform (22 mL) was added JV-chlorosuccinimide (0.34 g, 2.55 mmol). The reaction mixture was heated at reflux for 16 h and then cooled to room temperature. The reaction mixture was diluted with chloroform (50 mL), washed with water (30 mL), saturated aqueous sodium chloride solution (30 mL) and dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate -hexanes (1 : 9) as eluant to provide the title compound, a compound of the present invention, as an off-white solid (0.35 g, 98.0 area % purity by ΗPLC) melting at 143-145° C. 1H NMR (CDCl3): δ 7.35-7.29 (m, 3H), 7.10-7.06 (m, 2H), 6.90-6.83 (m, 2H), 2.33 (s, 3H). ESI MS m/z 339 (M+l).
EXAMPLE 6 Preparation of 2-bromo-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl-lH-imidazole
(Compound 740) To a mixture of l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl-lH-imidazole
(prepared by the method of Example 4) (0.300g, 0.97 mmol). The reaction mixture was heated at reflux for 16 h, and then cooled to room temperature. The reaction mixture was diluted with chloroform (20 mL), washed with water (5 mL) and saturated aqueous sodium chloride solution (5 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate -hexanes as eluant to provide the title compound, a compound of the present invention, as a light yellow solid (269 mg) melting at 183-185° C. 1H NMR (CDCl3): δ 7.35-7.31 (m, 3H), 7.09-7.06 (d, J = 8.7 Hz, 2H), 6.88-6.82 (t, J = 7.8
Hz, 2H), 2.31 (s, 3H). ESI MS m/z 383 (M+l). EXAMPLE 7
Preparation of l-(4-chlorophenyl)-5-(4-fluorophenyl)-2-methyl-lH-imidazole (Compound 4) Step A: Preparation of l-(4-chlorophenyl)-2 -methyl- lH-imidazole
To a mixture of l-chloro-4-iodobenzene (1.50 g, 6.30 mmol) in Λ/,Λ/-dimethylformamide (1O mL) was added cesium carbonate (3.50 g, 10.9 mmol), copper(I) iodide (0.10 g, 0.50 mmol), 2-methylimidazole (0.46 g, 5.66 mmol) and. (li?,2i?)-l,2-cyclohexanediamine (0.12 g, 1.00 mmol). The reaction mixture was heated at 120 0C for 16 h and then cooled to room temperature. The reaction mixture was diluted with ethyl acetate (80 mL), washed with water (2 x 30 mL) and saturated aqueous sodium chloride solution (4O mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes (0.5 : 9.5) as eluant to provide the title compound as a brown solid (0.60 g). 1H NMR (CDCl3): δ 7.48-7.44 (m, 2H), 7.26-7.22 (m, 2H), 7.05 (d, J = 16.8 Hz, 2H), 2.35 (s, 3H).
ESI MS m/z 193 (M+ 1).
Step B Preparation of l-(4-chlorophenyl)-5-(4-fluorophenyl)-2 -methyl- lH-imidazole
To a mixture of l-(4-chlorophenyl)-2 -methyl- lH-imidazo Ie (i.e. the product of Step A)
(0.700 g, 0.520 mmol) in Λ/,Λ/-dimethylformamide (10 mL) was added l-fluoro-4- iodobenzene (1.61 g, 7.30 mmol), tris(2-methylphenyl)phosphine (0.110 g, 0.360 mmol), cesium fluoride (1.10 g, 7.30 mmol) and palladium(II) acetate (0.041 g, 0.18 mmol). The reaction mixture was stirred under argon, heated at reflux for 16 h, and then cooled to room temperature. The reaction mixture was diluted with ethyl acetate (40 mL), washed with water (20 mL) and saturated aqueous sodium chloride solution (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography using methanol-dichloromethane (1 : 9) as eluant to provide the title compound, a compound of the present invention, as an off- white solid (0.20 g, 95.3 area % purity by ΗPLC) melting at 132-134 0C. 1H NMR (CDCl3): δ 7.42-7.39 (m, 2H), 7.11-7.06 (m, 3H), 7.05-6.99 (m, 2H), 6.95-6.87 (m, 2H), 2.31 (s, 3 H).
ESI MS m/z 287 (M+ 1).
EXAMPLE 8 Preparation of 4-chloro-l-(4-chlorophenyl)-5-(4-fluorophenyl)-2-methyl-lH-imidazole
(Compound 5) To a mixture of l-(4-chlorophenyl)-5-(4-fluorophenyl)-2-methyl-lH-imidazole (i.e. the product of Step B of Example 7) (0.100 g, 0.340 mmol) in chloroform (2.5 mL) was added JV-chlorosuccinimide (0.05 g, 0.36 mmol). The reaction mixture was heated at reflux for 16 h and then cooled to room temperature. The reaction mixture was diluted with chloroform (20 mL), washed with water (10 mL) and saturated aqueous sodium chloride solution (1O mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using ethyl acetate-hexanes (1 : 4) as eluant to provide the title compound, a compound of the present invention, as a yellow solid (0.065 g, 95.2 area % purity by HPLC) melting at 124-126 0C. 1H NMR (CDCl3): δ 7.40-7.36 (m, 2H), 7.14-7.07 (m, 2H), 7.06-7.03 (m, 2H), 6.99-6.92 (m,
2H), 2.29 (s, 3H). ESI MS m/z 322 (M+l). EXAMPLE 9
Preparation of 5-(2,6-difluoro-4-methoxyphenyl)- 1 -(3 ,5 -dimethoxyphenyl)-4-methyl- IH- imidazole (Compound 632) Step A: Preparation of Λ/-[(2,6-difluoro-4-methoxyphenyl)methylene]-3,5- dimethoxybenzenamine A mixture of 3,5-dimethoxybenzamine (2.00 g, 13.1 mmol) and 2,6-difluoro-4- methoxybenzaldehyde (2.30 g, 13.1 mmol) in toluene (40 mL) was heated at reflux overnight with use of a Dean-Stark trap for azeotropic removal of water. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to provide the title compound as a solid (4.00 g). 1H NMR (CDCl3): δ 8.56 (s, IH), 6.53 (m, 2H), 6.36 (m, 3H), 3.85 (s, 3H), 3.81 (s, 6H).
Step B Preparation of 5-(2,6-difluoro-4-methoxyphenyl)-l-(3,5-dimethoxyphenyl)-4- methyl- lH-imidazole
A mixture of Λ/-[(2,6-difluoro-4-methoxyphenyl)methylene]-3,5-dimethoxy- benzenamine (i.e. the product of Step A) (1.80 g, 6.0 mmol), l-[(l-isocyanoethyl)sulfonyl]- 4-methylbenzene (1.90 g, 9.0 mmol) and potassium tert-butoxidc in tetrahydrofuran (20 mL) was heated at reflux overnight. The reaction mixture was cooled and then concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.20 g). 1H NMR (CDCl3): δ 7.73 (s, IH), 6.45 (m, 2H), 6.38 (s, IH), 6.27 (s, 2H), 3.78 (s, 3H), 3.70 (m, 6H), 2.18 (s, 3H).
EXAMPLE 10 Preparation of 2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3,5-dimethoxyphenyl)-4- methyl-lH-imidazole (Compound 694) To a mixture of 5-(2,6-difluoro-4-methoxyphenyl)-l-(3,5-dimethoxyphenyl)-4-methyl- lH-imidazole (i.e. the product of Example 9) (0.280 g, 0.78 mmol) and hexachloroethane (1.10 g, 4.7 mmol) in tetrahydrofuran (5 mL) at -78 0C was added lithium diisopropylamide (1.0 M in tetrahydrofuran, 0.390 mL, 0.78 mmol). After 1 h more lithium diisopropylamide (1.0 M in tetrahydrofuran, 0.150 mL, 0.30 mmol) was added to the reaction mixture, stirring was continued for an additional 1 h, and then more lithium diisopropylamide (1.0 M in tetrahydrofuran, 0.150 mL, 0.30 mmol) was added to the reaction mixture. The reaction mixture was allowed to slowly warm to room temperature, stirred for 2.5 h, and then concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.011 g). 1H NMR (CDCl3): δ 6.42 (m, 3H), 6.31 (m, 2H), 3.77 (s, 3H), 3.72 (s, 6H), 2.13 (s, IH).
EXAMPLE 11 Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(3 -fluorophenyl)- lH-imidazole
(Compound 246) Step A: Preparation of 2,6-α-[(3-fluorophenyl)amino)]-4-methoxybenzeneacetonitrile A mixture of 3-fluoroaniline (1.15 g, 10.4 mmol), 2,6-difluoro-4- methoxybenzaldehyde (2.00 g, 11.6 mmol), potassium cyanide (2.70 g, 41.6 mmol) and indium chloride (2.30 g, 10.4 mmol) in tetrahydrofuran (40 mL) was stirred at room temperature overnight. The reaction mixture was diluted with water (about 100 mL) and extracted with ethyl acetate. The combined ethyl acetate extracts were concentrated under reduced pressure to provide the title compound as an oil, which was carried directly on to Step B. Step B Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3- fluorophenyl)- lH-imidazole To a mixture of 2,6-α-[(3-fluorophenyl)amino)]-4-methoxybenzeneacetonitrile (i.e. the product of Step A) (10.4 mmol) in dichloromethane (20 mL) was added Λ/-(chloromethylene)-Λ/-methylmethanaminium chloride (1.60 g, 12.5 mmol). The reaction mixture was heated to reflux for 3 h and then diluted with saturated aqueous sodium carbonate solution. The aqueous mixture was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (2.27 g). 1H NMR (CDCl3): δ 7.37 (m, IH), 7.13 (m, IH), 6.96 (m, 2H), 6.41 (d, 2H), 3.77 (s, 3H). EXAMPLE 12 Preparation of 2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(3 -fluorophenyl)- IH- imidazole (Compound 256)
A stirred mixture of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3-fluorophenyl)- lH-imidazole (i.e. the product of Step B of Example 11) (1.00 g, 3.0 mmol) and
N-bromosuccinimide (0.641 g, 3.6 mmol) in Λ/,iV-dimethylformamide (15 mL) was heated at
60 0C for 2.5 days. The reaction mixture was diluted with saturated aqueous sodium carbonate solution, and the resulting aqueous mixture was extracted with dichloromethane.
The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.67 g).
1H NMR (CDCl3): δ 7.37 (m, IH), 7.13 (m, IH), 7.13 (m, IH), 6.96 (m, 2H), 6.41 (d, 2H),
3.77 (s, 3H). EXAMPLE 13
Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(3-fluorophenyl)-2-methyl- IH- imidazole (Compound 280)
A mixture of 2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3-fluorophenyl)- lH-imidazole (i.e. the product of Example 12) (0.200 g, 0.490 mmol), trimethylboroxine (0.062 g, 0.490 mmol), cesium carbonate (0.479 g, 1.47 mmol) and dichlorobis(triphenylphosphine)palladium (0.035 g, 0.05 mmol) in dioxane (5 mL) and water (2 drops) was heated at reflux overnight. More trimethylboroxine (0.062 g, 0.490 mmol) and dichlorobis(triphenylphosphine)palladium (0.035 g, 0.05 mmol) were added to the reaction mixture, and the mixture was again heated at reflux overnight. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.090 g). 1H NMR (CDCl3): δ 7.35 (m, IH), 7.09 (m, IH), 6.94 (d, IH), 6.89 (m, IH), 6.39 (m, 2H), 3.76 (s, 3H), 2.31 (s, 3H).
EXAMPLE 14 Preparation of 4-bromo-5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluorophenyl)-lH-imidazole
(Compound 450)
Step A: Preparation of 2,6-α-[(4-fluorophenyl)amino)]-3-methoxybenzeneacetonitrile A mixture of 4-fluoroaniline (1.17 g, 10.6 mmol), 2,6-difluoro-3- methoxybenzaldehyde (2.0Og, 11.6 mmol), potassium cyanide (2.80 g, 42.4 mmol) and indium chloride (2.30 g, 10.4 mmol) in tetrahydrofuran (50 mL) was stirred at room temperature overnight. The reaction mixture was diluted with water (about 100 mL) and extracted with ethyl acetate. The combined ethyl acetate layers were concentrated under reduced pressure to provide the title compound as an oil, which was carried directly on to Step B. Step B Preparation of 4-bromo-5-(2,6-difluoro-3-methoxyphenyl)-l-(4- fluorophenyl)- lH-imidazole
To a mixture of 2,6-α-[(4-fluorophenyl)amino)]-3-methoxybenzeneacetonitrile (i.e. the product of Step A) (10.6 mmol) in dichloromethane (20 mL) was added
Λ/-(bromomethylene)-Λ/-methylmethanaminium bromide (2.80 g, 12.7 mmol). The reaction mixture was heated to 80 0C for one minute, then saturated aqueous sodium carbonate solution was added and the aqueous mixture was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (1.78 g).
1H NMR (CDCl3): δ 7.71 (m, IH), 7.15 (m, 2H), 7.05 (m, 2H), 6.96 (m, IH), 6.82 (m, IH), 3.85 (s, 3H).
EXAMPLE 15 Preparation of 2,4-dibromo-5-(2,6-difluoro-3-methoxyphenyl)- 1 -(4-fluorophenyl)- IH- imidazole (Compound 504)
A stirred mixture of 4-bromo-5-(2,6-difluoro-3-methoxyphenyl)-l-(4- fluorophenyl)lH-imidazole (i.e. the product of Step B of Example 14) (0.500 g, 1.3 mmol) and N-bromosuccinimide (0.285 g, 1.60 mmol) in Λ/,Λ/-dimethylformamide (15 mL) was heated at 60 0C overnight. More N-bromosuccinimide (0.250 g, 1.40 mmol) was added to the reaction mixture and the mixture was again heated at 60 0C overnight, after which time more N-bromosuccinimide (0.250 g, 1.40 mmol) was added and the mixture was again heated at 60 0C overnight. The reaction mixture was diluted with saturated aqueous sodium carbonate solution, and the aqueous mixture was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.36 g). 1H NMR (CDCl3): δ 7.19 (m, 2H), 7.07 (m, 2H), 6.95 (m, IH), 6.79 (m, IH), 3.83 (s, 3H). EXAMPLE 16 Preparation of 5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluorophenyl)-2,4-dimethyl-lH- imidazole (Compound 549)
A mixture of 2,4-dibromo-5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluorophenyl)-lH- imidazole (i.e. the product of Example 15) (0.314 g, 0.68 mmol), trimethylboroxine (0.085 g,
0.490 mmol), cesium carbonate (0.665 g, 2.04 mmol) and dichlorobis(triphenyl- phosphine)palladium (0.049 g, 0.07 mmol) in dioxane (5 mL) and water (2 drops) was heated at reflux for 3 days. More trimethylboroxine (0.085 g, 0.68 mmol) and dichlorobis
(triphenylphosphine)palladium (0.049 g, 0.70 mmol) were added at the reaction mixture, and the mixture was heated to reflux overnight. The reaction mixture was concentrated under reduced pressure and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.097 g).
1H NMR (CDCl3): δ 7.11 (m, 2H), 7.02 (m, 2H), 6.84 (m, IH), 6.73 (m, IH), 3.81 (s, 3H), 2.29 (s, 3H), 2.16 (s, 3H).
EXAMPLE 17 Preparation of 4-chloro- 1 -[3-(difluoromethoxy)phenyl]-5-(2,6-difluoro-3-methoxyphenyl)-2- ethenyl-lH-imidazole (Compound 583)
A mixture of 2-bromo-4-chloro-l-[3-(difluoromethoxy)phenyl]-5-(2,6-difluoro-3- methoxyphenyl)-lH-imidazole (prepared by a procedure analogous to Example 12),
2,4,6-trivinylcyclotriboroxane pyridine complex (0.103 g, 0.43 mmol), cesium carbonate
(0.420 g, 1.29 mmol) and dichlorobis(triphenylphosphine)palladium (0.028 g, 0.040 mmol) in dioxane (5 mL) and water (2 drops) was heated at reflux for 2.5 days. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (30 mg).
1H NMR (CDCl3): δ 7.37 (m, IH), 7.16 (m, IH), 7.05 (d, IH), 6.93 (m, 2H), 6.78 (m, IH), 6.35 (m, 3H), 5.43 (m, IH), 3.82 (s, 3H). EXAMPLE 18
Preparation of 4-chloro- 1 -(4-chlorophenyl)-5-(2,3 ,6-trifluorophenyl)- lH-imidazole-2- carbonitrile (Compound 57)
A mixture of 2-bromo-4-chloro-l-(4-chlorophenyl)-5-(2,3,6-trifluorophenyl)-lH- imidazole (prepared by a procedure analogous to Example 12), zinc cyanide (0.033 g, 0.280 mmol), dichloro[l,r-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane complex (1 :1) (0.016 g, 0.02 mmol) and tetramethylethylenediamine (0.01 g, 0.095 mmol) in
Λ/,Λ/-dimethylformamide (3 mL) was heated at 60 0C in a Biotage Initiator™ microwave apparatus for 200 seconds. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.030 g) melting at 147-149 0C. 1H NMR (CDCl3): δ 7.45 (m, 2H), 7.28 (m, IH), 7.21 (m, 2H), 6.89 (m, IH).
EXAMPLE 19 Preparation of 4-chloro-5-(2,6-difluorophenyl)-2-ethynyl-l-(3-fluorophenyl)-lH-imidazole
(Compound 47) Step A: Preparation of 4-chloro-5-(2,6-difluorophenyl)-l-(3-fluorophenyl)-2-[2- (trimethylsilyl)ethynyl]- lH-imidazole
A mixture of 2-bromo-4-chloro-5-(2,6-difluorophenyl)-l-(3-fluorophenyl)-lH- imidazole (prepared by a procedure analogous to Example 12) (0.823 g, 2.10 mmol), dichlorobis(triphenylphosphine)palladium (0.147 g, 0.21 mmol), copper(I) iodide (0.081 g, 0.74 mmol) in triethylamine (15 mL) was stirred for 5 minutes while nitrogen gas flowed through a syringe needle below the surface of the reaction mixture. Ethynyltrimethyl silane (0.216 g, 2.2 mmol) was added to the reaction mixture, stirring was continued for 2 h, and then the mixture was heated at reflux overnight. More dichlorobis(triphenylphosphine)palladium (0.147 g, 0.21 mmol) and ethynyltrimethylsilane (0.216 g, 2.2 mmol) were added to the reaction mixture, and the mixture was heated at reflux for 4 h. The reaction mixture was diluted with saturated aqueous sodium carbonate solution and extracted with ethyl acetate, and the combined organic layers were washed with saturated aqueous ethylenediaminetetraacetic acid, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (0.244 g).
1H NMR (CDCl3): δ 7.34 (m, 2H), 7.05 (m, 3H), 6.89 (m, 2H), 0.13 (s, 9H).
Step B Preparation of 4-chloro-5-(2,6-difluorophenyl)-2-ethynyl-l-(3-fluorophenyl)- lH-imidazole A mixture of 2-bromo-4-chloro-5-(2,6-difluorophenyl)-l-(3-fluorophenyl)-lH- imidazole (i.e. the product of Step A) (0.231 mg, 0.570 mmol) in a solution of sodium hydroxide and methanol (1%, w/w, 2 mL) was stirred for 3 h at room temperature. The reaction mixture was diluted with ethyl acetate and saturated aqueous ammonium chloride solution, the layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound, a compound of the present invention, as a solid (0.135 g). 1H NMR (CDCl3): δ 7.35 (m, 2H), 7.11 (m, IH), 7.00 (m, 2H), 6.89 (m, 2H), 3.17 (s, IH). EXAMPLE 20 Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(4-fluorophenyl)- IH- imidazole-2-carboxaldehyde (Compound 276)
To a stirred mixture of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluorophenyl)- lH-imidazole (prepared by a procedure analogous to Example 11) (1.35 g, 4.0 mmol) in diethyl ether (10 mL) at 0 0C was added lithium diisopropylamide (2 M in tetrahydrofuran,
2.2 mL, 4.4 mmol). The reaction mixture was stirred for 1 h at 0 0C, and then
Λ/,Λ/-dimethylformamide (0.47 mL, 6.0 mmol) was added. After an additional 1 h of stirring at 0 0C, the reaction mixture was allowed to warm to room temperature. After 1 h, the reaction mixture was diluted with aqueous citric acid solution (20%, 30 mL) and extracted with diethyl ether (100 mL). The organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by flash column chromatography on silica gel (0 to 20% gradient of ethyl acetate in n-butyl chloride as eluant) to provide the title compound, a compound of the present invention, as a pale- yellow solid (0.397 g).
1H NMR (CDCl3): δ 9.71 (s, IH), 7.19-7.17 (m, 2H), 7.06 (t, J= 7.5 Hz, 2H), 6.44 (m, IH),
6.42 (s, IH), 3.78 (s, 3H). ESI MS m/z 367 (M+l).
EXAMPLE 21 Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l -(4-fluorophenyl)- IH- imidazole-2-methanol (Compound 298)
To a mixture of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluorophenyl)-lH- imidazole-2-carboxaldehyde (i.e. the product of Example 20) in methanol (10 mL) was added sodium borohydride (1.10 g, 2.64 mmol). After 1 h, water (25 mL) was added to the reaction mixture, and the aqueous mixture was extracted with diethyl ether (50 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by flash column chromatography on silica gel (0 to 30% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as an off- white solid (0.156 g). 1H NMR (CDCl3): δ 7.26-7.25 (m, 2H), 7.07 (t, J= 7.5 Hz, 2H), 6.42 (s, IH), 6.39 (s, IH), 4.54 (d, J= 3 Hz, 2H), 4.13 (t, J= 6 Hz, IH), 3.77 (s, 3H).
EXAMPLE 22 Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-2-(fluoromethyl)-l-(4- fluorophenyl)-lH-imidazole (Compound 331) To a mixture of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluorophenyl)-lH- imidazole -2 -methanol (i.e. the product of Example 21) in dichloromethane (2 mL) was added diethylaminosulfur trifluoride (60 μL, 0.45 mmol). After 2 h, the reaction mixture was diluted with water, extracted with dichloromethane (100 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by flash column chromatography on silica gel (0 to 20% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a white solid (0.031 g).
1H NMR (CDCl3): δ 7.25-7.23 (m, 2H), 7.08 (t, J = 6 Hz, 2H), 6.43 (s, IH), 6.41 (s, IH), 5.25 (s, IH), 5.13 (s, IH), 3.78 (s, 3H).
EXAMPLE 23
Preparation of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(4-fluorophenyl)- IH- imidazole-2-carboxaldehyde oxime (Compound 349)
To a mixture of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluorophenyl)-lH- imidazole-2-carboxaldehyde (i.e. the product of Example 20) in methanol (2 mL) was added a solution of hydroxylamine hydrochloride (0.165 g, 2.4 mmol) and sodium carbonate (0.127 g, 1.2 mmol) in water (1 mL). The reaction mixture was heated at 70 0C for 1 h and then allowed to cool to room temperature. After 48 h, the reaction mixture was filtered, and the solid collected was washed with methanol (2 mL) to provide the title compound, a compound of the present invention, as a shiny-white solid (0.148 g).
1H NMR (CDCl3): δ 11.0 (br s, IH), 7.42 (s, IH), 6.82-6.79 (t, 2H), 6.68 (t, J = 6 Hz, 2H), 6.07 (s, IH), 6.05 (s, IH), 3.35 (s, 3H). EXAMPLE 24
Preparation of 4-bromo-2-(bromoethyl)- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)- IH- imidazole (Compound 475)
A mixture of 2-bromo-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl-lH- imidazole (i.e. the product of Example 6) (1.00 g, 2.6 mmol), Λ/-bromosuccinimide (0.510 g, 2.87 mmol) and 2,2'-azobis(2-methylpropionitrile) (0.021 g, 130 mmol) in carbon tetrachloride (8 mL) was heated at reflux overnight. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.940 g). 1H NMR (CDCl3): δ 7.35 (m, 3H), 7.24 (m, 2H), 6.87 (m, 2H), 4.36 (s, 2H).
EXAMPLE 25 Preparation of 4-bromo- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)- lH-imidazole-2- acetonitrile (Compound 509)
A mixture of 4-bromo-2-(bromoethyl)-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH- imidazole (i.e. the product of Example 24) (1.00 g, 2.6 mmol), potassium cyanide (0.105 g,
1.62 mmol) and 18-crown-6 (0.057 g, 0.216 mmol) in acetonitrile (3 mL) was heated at
40 0C overnight. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.105 g). 1H NMR (CDCl3): δ 7.38 (m, 3H), 7.18 (m, 2H), 6.89 (m, 2H), 3.76 (s, 2H). EXAMPLE 26
Preparation of methyl 4-bromo-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole-2- acetate (Compound 544)
To a mixture of thionyl chloride (0.232 mL) in methanol (5 mL) was added 4-bromo- l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole-2-acetonitrile (i.e. the product of Example 25) (0.650 g 1.59 mmol). The reaction mixture was heated at reflux overnight, then more thionyl chloride (0.5 mL) was added, and the mixture was heated at reflux for an additional 8 h. The reaction mixture was diluted with ethyl acetate and washed with water (2x), and the ethyl acetate mixture was neutralized by the addition of saturated aqueous sodium bicarbonate solution. The aqueous mixture was extracted with ethyl acetate (2x), and the combined organic layers were washed with saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.470 g). 1H NMR (CDCl3): δ 7.32 (m, 3H), 7.15 (m, 2H), 6.86 (dd, 2H), 3.70 (s, 2H), 3.66 (s, 3H).
EXAMPLE 27 Preparation of 4-bromo-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole-2-acetic acid (Compound 570)
A mixture of methyl 4-bromo-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)lH- imidazole-2-acetate (i.e. the product of Example 26) (0.100 g, 0.226 mmol) and lithium hydroxide monohydrate (0.019 g, 0.453 mmol) in tetrahydrofuran and water (1 :1, 2 mL) was stirred for 20 minutes, and then hydrochloric acid (1 N, 0.45 mL) was added. The reaction mixture was extracted with ethyl acetate (3x), and the combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.037 g).
1H NMR (CD3COCD3): δ 7.51 (m, 3H), 7.35 (m, 2H), 7.05 (m, 2H), 3.77 (s, 2H). EXAMPLE 28 Preparation of 4-bromo- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)-Λ/-methyl- lH-imidazole-
2-acetamide (Compound 571)
A mixture of 4-bromo-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole-2- acetic acid (i.e. the product of Example 27) (0.217 g, 0.507 mmol), methylamine (2 M in tetrahydrofuran, 0.505 mL, 1.01 mmol) and //-(S-dimethylaminopropyl)-^- ethylcarbodiimide hydrochloride (0.117 g, 0.609 mmol) in pyridine (4 mL) and dichloromethane (3 mL) were stirred at room temperature overnight. More methylamine
(2 M in tetrahydrofuran, 0.505 mL, 1.01 mmol), ^-(S-dimethylaminopropyl)-^- ethylcarbodiimide hydrochloride (0.117 g, 0.609 mmol) and pyridine (1 mL) were added to the reaction mixture and stirring was continued for 4 h. The reaction mixture was diluted with ethyl acetate and then washed with water (3x) and saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.063 g).
1H NMR (CDCl3): δ 7.52 (br s, IH), 7.34 (m, 3H), 7.11 (m, 2H), 6.88 (m, 2H), 3.54 (s, 2H),
2.87 (d, 3H).
EXAMPLE 29 Preparation of 3-[4-chloro-l-(4-chlorophenyl)-lH-imidazol-5-yl]-2,4-difluorobenzonitrile
(Compound 386)
A mixture of 5-(3-bromo-2,6-difluorophenyl)-4-chloro-l-(4-chlorophenyl)-lH- imidazole (prepared a procedure analogous to Example 11) (0.440 g, 0.490 mmol), zinc cyanide (0.058 g, 0.490 mmol), dichloro[l,r-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane complex (1 :1) (0.044 g, 0.0545 mmol) and N5N^V5TV- tetramethylethylenediamine (0.022 g, 0.218 mmol) in dimethylacetamide (3 mL) was heated at 200 0C in a Biotage Initiator™ microwave apparatus for 5 minutes. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.217 g). 1H NMR (CDCl3): δ 7.72 (s, IH), 7.69 (m, IH), 7.38 (m, 2H), 7.07 (m, 3H).
EXAMPLE 30
Preparation of 3-[2-bromo-4-chloro-l-(4-chlorophenyl)-lH-imidazol-5-yl]-2,4- difluorobenzonitrile (Compound 419)
A mixture of 3-[4-chloro-l-(4-chlorophenyl)-lH-imidazol-5-yl]-2,4- difluorobenzonitrile (i.e. the product of Example 29) (0.217 g, 0.62 mmol) and JV-bromosuccinimide (0.165 g, 0.930 mmol) in dimethylformamide (4 mL) was heated at 60 0C overnight. More JV-bromosuccinimide (0.386 g, 2.17 mmol) was added portionwise to the reaction mixture, and the mixture was heated at 60 0C overnight again. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.196 g). 1H NMR (CDCl3): δ 7.67 (m, IH), 7.40 (m, 2H), 7.13 (m, 2H), 7.03 (m, IH). EXAMPLE 31
Preparation of 3-[4-chloro- 1 -(4-chlorophenyl)-2-methyl- lH-imidazol-5-yl]-2,4- difluorobenzonitrile (Compound 430)
A mixture of 3-[2-bromo-4-chloro-l-(4-chlorophenyl)-lH-imidazol-5-yl]-2,4- difluorobenzonitrile (i.e. the product of Example 30) (0.150 g, 0.350 mmol), trimethylboroxine (0.088 g, 0.700 mmol), cesium carbonate (0.342 g, 1.05 mmol) and dichlorobis(triphenylphosphine)palladium (0.025 g, 0.035 mmol) in dioxane (4 mL) and water (2 drops) was heated at reflux for 3 h. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.088 g).
1H NMR (CDCl3): δ 7.65 (m, IH), 7.39 (m, 2H), 7.09 (m, 2H), 7.01 (m, IH), 2.32 (s, 3H).
EXAMPLE 32
Preparation of 4-[4-chloro-2-methyl- 1 -(4-methylphenyl)- lH-imidazol-5-yl]-3,5- difluorophenol (Compound 624) To a stirred mixture of 4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-l-(4- methylphenyl)-lH-imidazole (prepared by a procedure analogous to Example 13) (0.500 g, 1.43 mmol) in dichloromethane (10 mL) at -78 0C was added tribromoborane (1 M in dichloromethane, 4.3 mL, 4.30 mmol). The reaction mixture was allowed to warm to room temperature, and stirred overnight. More tribromoborane (1 M in dichloromethane, 1.4 mL, 1.40 mmol) was added to the reaction mixture at room temperature, and stirring was continued for 4 h. Hydrochloric acid (1 N, 8.0 mL) was added to the reaction mixture, and then the aqueous mixture was brought to a basic pH by the addition of saturated aqueous sodium carbonate solution. The aqueous mixture was extracted with ethyl acetate, and the extract was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.41 g). 1H NMR (CDCl3): δ 10.68 (s, IH), 7.24 (d, 2H), 7.09 (d, 2H), 6.43 (m, 2H), 2.31 (s, 3H), 2.18 (s, 3H).
EXAMPLE 33
Preparation of 3-[4-[4-chloro-2-methyl-l-(4-methylphenyl)-lH-imidazol-5-yl]-3,5- difluorophenoxy]-Λ/-methyl-l-propanamide hydrochloride (Compound 734)
Step A: Preparation of phenylmethyl Λ/-[3-[4-[4-chloro-2-methyl-l-(4-methylphenyl)- lH-imidazol-5-yl]-3,5-difluorophenoxy]propyl]-Λ/-methylcarbamate A mixture of 4-[4-chloro-2-methyl-l-(4-methylphenyl)-lH-imidazol-5-yl]-3,5- difluorophenol (i.e. the product of Example 32) (0.200 g, 0.598 mmol) and 4 A molecular sieves (1.55 g) in N,Λ/-dimethylformamide (3 mL) was stirred at room temperature for 3 h, and then a solution of phenylmethyl Λ/-(3-chloropropyl)-Λ/-methylcarbamate (prepared by the method described in PCT Publication WO 2007/149448) (0.434 g, 1.80 mmol) and tetrabutylammonium iodide (0.044 g, 0.120 mmol) in Λ/,Λ/-dimethylformamide (1 mL) was added. After 15 minutes, cesium carbonate (0.584 g, 1.80 mmol) was added to the reaction mixture. After 15 minutes, the reaction mixture was heated at 75 0C for 2 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (210 mg). ESI MS m/z 541 (M+l).
Step B Preparation of 3-[4-[4-chloro-2-methyl- 1 -(4-methylphenyl)- lH-imidazol-5- yl]-3 ,5 -difluorophenoxy] -//-methyl- 1 -propanamide hydrochloride
A mixture of phenylmethyl Λ/-[3-[4-[4-chloro-2-methyl-l-(4-methylphenyl)-lH- imidazol-5-yl]-3,5-difluorophenoxy]propyl]-N-methylcarbamate (i.e. the product of Step A) (0.197 g, 0.365 mmol), hydrochloric acid (2 M in diethyl ether, 1 mL) and methanol (30 mL) was purged with nitrogen for 30 minutes, and then palladium on carbon (10%, 0.058 g,
0.0547 mmol) was added and the nitrogen purge was maintained for an additional 15 minutes. After 15 minutes, the nitrogen purge was stopped and a balloon filled with hydrogen was connected to the reaction flask, and the reaction mixture was stirred at room temperature for 3 h. The reaction mixture was purged with nitrogen and the palladium on carbon catalyst was removed by filtering through a bed of sand and Celite® (diatomaceous filter aid) on a sintered glass frit funnel. The filtrate was concentrated under reduced pressure to provide the title compound, a compound of the present invention, as a solid
(0.14O g). 1H NMR (DMSO-J6): δ 8.90 (br s, 2H), 7.25 (d, 2H), 7.11 (d, 2H), 6.76 (d, 2H), 4.08 (t, 2H), 2.98 (m, 2H), 2.54 (m, 3H), 2.31 (s, 3H), 2.19 (s, 3H), 2.04 (d, 2H). EXAMPLE 34 Preparation of 5-[4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-l-yl]-2-
(trifluoromethyl)pyridine
Step A: Preparation of N-[(2,6-difluoro-4-methoxyphenyl)methylene]-6- (trifluoromethyl)-3 -pyridinamine
A mixture of 6-(trifluoromethyl)-3 -pyridinamine (5.00 g, 30.8 mmol) and 2,6-difluoro-
4-methoxybenzaldehyde (5.30 g, 30.8 mmol) in toluene (100 mL) was heated to reflux for
2.5 days. Then the reaction mixture was concentrated under reduced pressure to provide the title compound as a solid (9.9 g). 1H NMR (CDCl3): δ 8.56 (s, IH), 8.52 (d, IH), 7.71 (d, IH), 7.60 (m, IH), 6.57 (m, 2H),
3.88 (s, 3H). Step B Preparation of 5-[5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 -yl]-2-
(trifluoromethyl)pyridine
A mixture of N-[(2,6-difluoro-4-methoxyphenyl)methylene]-6-(trifluoromethyl)-3- pyridinamine (i.e. the product of Step A), l-[(l-isocyanoethyl)sulfonyl]-4-methylbenzene
(4.6 g, 23.7 mmol) and potassium carbonate (4.4 g, 31.6 mmol) in dimethoxyethane (20 mL) and methanol (20 mL) was heated at 75 0C overnight. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a solid (4.63 g).
1H NMR (CDCl3): δ 8.59 (m, IH), 7.86 (s, IH), 7.71 (m, 2H), 7.33 (m, IH), 6.46 (m, 2H),
3.80 (s, 3H). Step C Preparation of 5-[4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 - yl]-2-(trifluoromethyl)pyridine A mixture of 5-[5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-l-yl]-2-
(trifluoromethyl)pyridine (i.e. the product of Step B) (1.50 g, 4.20 mmol), JV-chlorosuccinimide (0.56 g, 4.2 mmol) and 2,2'-azobis(2-methylpropionitrile) (0.038 g, 0.230 mmol) in carbon tetrachloride (8 mL) was heated at 65 0C for 3.5 days. The reaction mixture was diluted with saturated aqueous sodium carbonate solution and extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.650 g). 1H NMR (CDCl3): δ 8.59 (m, IH), 7.73 (m, 3H), 6.49 (m, 2H), 3.82 (s, 3H). EXAMPLE 35 Preparation of 5-[2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 -yl]-2-
(trifluoromethyl)pyridine (Compound 707)
A mixture of 5-[4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-l-yl]-2- (trifluoromethyl)pyridine (i.e. the product of Step C of Example 34) (0.650 g, 1.70 mmol) and N-bromosuccinimide (0.356 g, 2.0 mmol) in N,Λ/-dimethylformamide (10 mL) was heated at 65 0C overnight. More N-bromosuccinimide (0.195 g, 1.1 mmol) was added to the reaction mixture, and the mixture was heated at 65 0C for 2.5 days. The reaction mixture was diluted with saturated sodium carbonate solution and extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.108 g). 1H NMR (CDCl3): δ 8.58 (s, IH), 7.78 (m, 2H), 6.43 (m, 2H), 3.79 (s, 3H). EXAMPLE 36
Preparation of 5-[4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH-imidazol-l -yl]-2-
(trifluoromethyl)pyridine (Compound 713)
A mixture of 5-[2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-l- yl]-2-(trifluoromethyl)pyridine (i.e. the product of Example 35) (0.093 g, 0.20 mmol), trimethylboroxine (0.025 g, 0.20 mmol), cesium carbonate (0.195 g, 0.60 mmol) and dichlorobis(triphenylphosphine)palladium (0.014 g, 0.20 mmol) in dioxane (3 mL) and water
(1 drop) was heated to reflux overnight. Then the reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.021 g).
1H NMR (CDCl3): δ 8.55 (s, IH), 7.75 (m, IH), 7.69 (m, IH), 6.42 (m, 2H), 3.78 (s, 3H), 2.35 (s, 3H).
EXAMPLE 37
Preparation of 2-chloro-5-[l-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol-5- yl]pyridine (Compound 685)
Step A: Preparation of Λ/-[(6-chloro-3-pyridinyl)methylene]-2,6-difluoro-4- methoxybenzenamine
To a mixture of 2,6-difluoro-4-methoxybenzenamine (0.98 g, 6.9 mmol) in toluene
(2O mL) was added 6-chloro-3-pyridinecarboxaldehyde (1.0 g, 6.3 mmol). The reaction mixture was heated at reflux with the use of a Dean-Stark trap for azeotropic removal of water. After 16 h the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting material was dried in a vacuum oven at 55 0C overnight to provide the title compound as a light brown solid (1.66 g).
1H NMR (CDCl3): δ 8.74 (s, IH), 8.73 (d, J = 2.44 Hz, IH), 8.32 (dd, J = 2.20 Hz, J =
8.29 Hz, IH), 7.44 (d, J= 8.29 Hz, IH), 6.59-6.52 (m, 2H), 3.82 (s, 3H). 1F NMR (CDCl3): δ-121.48 to 121.40 (m, 2F).
Step B Preparation of 2-chloro-5-[l-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH- imidazol-5 -yl]pyridine
To a mixture of Λ/-[(6-chloro-3-pyridinyl)methylene]-2,6-difluoro-4- methoxybenzenamine (i.e. the product of Step A) (1.66 g, 5.9 mmol) in tetrahydrofuran (15 mL) was added /?-toluenesulfonylmethyl isocyanide (1.35 g, 6.5 mmol) and potassium te/t-butoxide (0.86 g, 7.7 mmol). The reaction mixture was heated at 85 0C for 4 h, cooled, and concentrated. The resulting material was diluted with ethyl acetate and washed with saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered and concentrated. The resulting material was purified by medium pressure liquid chromatography on silica gel (ethyl acetate in hexanes), and then triturated with n-butyl chloride-hexanes as eluant to provide the title compound, a compound of the present invention, as a tan solid (0.50 g) melting at 117-118 0C.
1H NMR (CDCl3): δ 8.16 (d, J = 2.44 Hz, IH), 7.55 (s, IH), 7.44 (dd, J = 2.68 and 8.29 Hz, IH), 7.28 (dd, J = 0.49 and 8.29 Hz, IH), 6.54-6.48 (m, 2H), 3.81 (s, 3H), 2.33 (s, 3H).
1FNMR (CDCl3): δ-118.21 to -118.15 (m, 2F).
EXAMPLE 38
Preparation of 2-chloro-5-[2-chloro-l-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH- imidazol-5-yl]pyridine (Compound 696) To a mixture of 2-chloro-5-[l-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol-
5-yl]pyridine (i.e. the product of Step B of Example 37) (0.150 g, 0.45 mmol) in Λ/,Λ/-dimethylformamide (2.0 mL) was added JV-chlorosuccinimide (0.066 g, 0.49 mmol), and the reaction mixture was heated at 60 0C. After 30 minutes, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (40 mL), and washed with water and saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, (0.108 g) as an off-white solid melting at 94-95 0C. 1H NMR (CDCl3): δ 8.17 (d, J= 2.20 Hz, IH), 7.43 (dd, J= 8.29 Hz, J= 2.44 Hz, IH), 7.26 (d, J= 8.54 Hz, IH), 6.53 (d, J= 9.02 Hz, 2H), 3.82 (s, 3H), 2.28 (s, 3H). EXAMPLE 39 Preparation of 3-bromo-5-(4-chlorophenyl)-4-(2,6-difluorophenyl)-l-methyl-lH-pyrazole
(Compound 125)
Step A: Preparation of l-(4-chlorophenyl)-2-(2,6-difluorophenyl)ethanone A mixture of 2,6-difluorophenylacetic acid (5.63 g, 31.1 mmol) and thionyl chloride
(4.5 mL) in toluene was heated at reflux for 4 h, after which time the reaction mixture was allowed to cool to room temperature and stirred for 1 h. The reaction mixture was concentrated under reduced pressure, diluted with carbon tetrachloride (50 mL), and again concentrated under reduced pressure. To a stirred mixture of the resulting material in chlorobenzene (17.5 mL) was added aluminum chloride (5 g) portionwise such that the reaction temperature was maintained at about 30 0C. Upon completion of the addition, the reaction mixture was heated at 50 ° to 70 0C for 2 h, and then stirred at room temperature overnight. The reaction mixture was poured portionwise into a slurry of ice/hydrochloric acid (1 N), extracted with toluene and concentrated under reduced pressure. The resulting material was diluted with methanol (50 mL), concentrated under reduced pressure, and then partitioned between ethyl acetate and aqueous sodium hydroxide solution (1 N). The organic layer was separated, and the aqueous sodium hydroxide layer was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound as a brown solid (1.75 g). 1HNMR (CDCl3) δ 7.98 (d, 2H), 7.47 (d, 2H), 7.35-7.22 (m, IH), 6.97-6.87 (m, 2H), 4.34
(s, 2H). Step B Preparation of l-(4-chlorophenyl)-2-(2,6-difluorophenyl)-3-(dimethylamino)-
2-propen-l-one
A mixture of l-(4-chlorophenyl)-2-(2,6-difluorophenyl)ethanone (i.e. the product of Step A) (0.5 g, 1.9 mmol) and Λf,Λ/-dimethylformamide dimethyl acetal (3.7 mL, 28.0 mmol) in toluene (34 mL) was heated at reflux overnight. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by medium pressure liquid chromatography on silica gel (20:80 to 50:50 gradient of ethyl acetate in hexanes as eluant) to provide of the title compound as a yellow solid (0.49 g). 1H NMR (CDCl3): δ 7.51 (br s, IH), 7.39 (d, 2H), 7.28-7.17 (m, 3H), 6.84-6.78 (m, 2H),
2.84 (br s, 6H). Step C Preparation of 3-(4-chlorophenyl)-4-(2,6-difluorophenyl)-lH-pyrazole
A mixture of l-(4-chlorophenyl)-2-(2,6-difluorophenyl)-3-(dimethylamino)-2-propen- 1-one (i.e. the product of Step B) (0.43 g, 1.34 mmol) and hydrazine monohydrochloride (0.14 g, 2.0 mmol) in ethanol (20 mL) was heated at reflux overnight. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by medium pressure liquid chromatography on silica gel (20:80 to 40:60 gradient of ethyl acetate in hexanes as eluant) to provide of the title compound as a yellow oil (0.40 g). 1H NMR (CDCl3): δ 7.70 (s, IH), 7.34 (d, 2H), 7.30-7.23 (m, 3H), 6.92 (m, 2H). Step D Preparation of 3-bromo-5-(4-chlorophenyl)-4-(2,6-difluorophenyl)-lH- pyrazole
To a stirred mixture of 3-(4-chlorophenyl)-4-(2,6-difluorophenyl)-lH-pyrazole (i.e. the product of Step C) (0.40 g, 1.38 mmol) in dichloromethane (10 mL) at 0 0C was added Λ/-bromosuccinimide (0.24 g, 1.38 mmol) portionwise. The reaction mixture was stirred at room temperature overnight and then cooled to 0 0C, and more N-bromosuccinimide (0.12 g, 0.69 mmol) was added. After stirring for 6 h at room temperature, the reaction mixture was cooled to 0 0C and more N-bromosuccinimide (0.12 g, 0.69 mmol) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with water, stirred for 5 minutes, and then extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was triturated with n-butyl chloride -hexanes and filtered to provide the title compound as a white solid (0.41 g). 1H NMR (CDCl3): δ 7.41-7.28 (m, 3H), 7.26 (d, 2H), 7.03-6.90 (m, 2H).
Step E Preparation of 3-bromo-5-(4-chlorophenyl)-4-(2,6-difluorophenyl)-l-methyl- lH-pyrazole
To a stirred mixture of 3-bromo-5-(4-chlorophenyl)-4-(2,6-difluorophenyl)-lH- pyrazole (i.e. the product of Step D) (0.35 g, 0.95 mmol) in Λf,Λ/-dimethylformamide (5 mL) at 0 0C was added sodium hydride (60% in mineral oil, 0.04 g, 0.95 mmol) portionwise. The reaction mixture was stirred for 5 minutes, then methyl iodide (0.67 g, 4.7 mmol) was added, and the mixture was allowed to warm to room temperature and stir for 20 minutes. The reaction mixture was poured into water and extracted with ethyl acetate (2x). The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by medium pressure liquid chromatography on silica gel (3:97 to 12:88 gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (12.6 mg). 1H NMR (CDCl3): δ 7.35 (d, 2H), 7.31-7.23 (m, IH), 7.17 (d, 2H), 6.91-6.82 (m, 2H), 3.83 (s, 3H). EXAMPLE 40
Preparation of 5-(2,6-difluorophenyl)-4-(3-fluorophenyl)-l,3-dimethyl-lH-pyrazole
(Compound 60) Step A: Preparation of 5-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazole
To a solution of glacial acetic acid (2.2 mL) was added l-(2,6-difluorophenyl)-l,3- butanedione (prepared by the method described in Japanese Patent Application Publication
JP 2001/048826) (1.0 g, 5.1 mmol) and JV-methylhydrazine (0.23 g, 5.1 mmol). The reaction mixture was heated at reflux for 4 h and then concentrated under reduced pressure. The resulting residue was purified by medium pressure liquid chromatography on silica gel (100:0 to 20:80 gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a white solid (0.26 g).
1H NMR (CDCl3): δ 7.43-7.37 (m, IH), 7.06-6.98 (m, 2H), 6.17 (s, IH), 3.71 (s, 3H), 2.33 (s, 3H).
Step B Preparation of 5-(2,6-difluorophenyl)-4-iodo- 1 ,3-dimethyl- lH-pyrazole
A mixture of 5-(2,6-difluorophenyl)-l,3-dimethyl-lH-pyrazole (i.e. the product of Step A) (0.20 g, 0.96 mmol) and TV-iodosuccinimide (0.22 g, 0.96 mmol) in Λ/,Λ/-dimethylformamide (5 mL) was heated at 90 0C overnight. The reaction mixture was allowed to cool to room temperature and then partitioned between water and ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by medium pressure liquid chromatography on silica gel (5:95 to 20:80 gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a light brown oil (0.22 g).
1H NMR (CDCl3): δ 7.55-7.42 (m, IH), 7.10-7.03 (m, 2H), 3.74 (s, 3H), 2.32 (s, 3H). Step C Preparation of 5-(2,6-difluorophenyl)-4-(3-fluorophenyl)-l,3-dimethyl-lH- pyrazole To toluene (5 mL) was added 5-(2,6-difluorophenyl)-4-iodo-l,3-dimethyl-lH-pyrazole (i.e. the product of Step B) (0.22 g, 0.66 mmol), 3-fiuorophenylboronic acid (0.18 g, 1.32 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.02 g, 0.02 mmol), 2- dicyclohexylphosphino-2',6'-dimethoxybiphenyl (0.04 g, 0.09 mmol), and potassium phosphate (0.43 g, 2.0 mmol), and the mixture was then heated at 100 0C overnight. The reaction mixture was allowed to cool to room temperature, and then concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (5:95 to 30:70 gradient of ethyl acetate in hexanes as eluant) to provide a solid. The solid was triturated with n-butyl chloride, filtered and air-dried to provide the title compound, a compound of the present invention, as an off-white solid (0.08 g)- 1H NMR (CDCl3): δ 7.45-7.38 (m, IH), 7.28-7.20 (m, 2H), 7.04-6.79 (m, 4H), 3.71 (s, 3H),
2.36(s, 3H).
EXAMPLE 41 Preparation of 4-(2-chloro-4-fluorophenyl)-5-[(2,4-difluorophenyl)methyl]- 1 ,3-dimethyl- IH- pyrazole (Compound 313) Step A: Preparation of 4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine
To a stirred mixture of sodium hydride (60 % in mineral oil, 3.5 g, 88 mmol) in xylenes (34 mL) at 50 0C was added ethanol (2O mL, 34 mmol) dropwise over about 15 minutes while maintaining an atmosphere of nitrogen. A solution of 2-chloro-4- fluorophenylacetonitrile (4.8 g, 28 mmol) and ethyl acetate (20 mL, 38 mmol) in xylenes (6 mL) was added dropwise over 15 minutes to the reaction mixture, and the mixture was heated at reflux for 2 h, then allowed to cool to room temperature. The reaction mixture was diluted with water (50 mL) and extracted with hexanes (50 mL). The aqueous layer was then acidified to pH 4 with aqueous hydrochloric acid (3 N) solution and extracted with diethyl ether (3 x 100 mL). The combined diethyl ether layers were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a tan solid (4.6 g). To a of mixture of the tan solid in ethanol (15 mL) was added acetic acid (3 mL) and methyl hydrazine (1.2 mL, 22 mmol), and the mixture was heated at reflux for 3 h, allowed to cool, and concentrated under reduced pressure. The resulting residue was triturated with ethyl acetate (about 5 mL) and filtered through a glass frit funnel, and the solid collected was air-dried to provide the title compound as a white solid (2.4 g). 1H NMR (CD3COCD3): δ 7.35-7.30 (m, 2H), 7.14 (m, IH), 4.43 (br s, 2H), 3.60 (s, 3H),
1.94 (s, 3H). Step B Preparation of 5-bromo-4-(2-chloro-4-fluorophenyl)- 1 ,3-dimethyl- IH- pyrazole To a mixture of 4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH-pyrazol-5-amine (i.e. the product of Step A) (2.4 g, 10 mmol) in acetonitrile (50 mL) was added copper(II) bromide (3.94 g, 17.7 mmol). The reaction mixture was cooled to about 0 0C with an ice-water bath, and then tert-butyi nitrite (90% technical grade, 2.33 mL, 17.7 mmol) was added dropwise over 5 minutes. The reaction mixture was allowed to warm slowly to room temperature. Aqueous hydrochloric acid solution (1 N, 20 mL) and ethyl acetate (20 mL) were added to the reaction mixture, and then the mixture was filtered through a pad (2 cm) of Celite® (diatomaceous filter aid). The Celite® pad was washed with ethyl acetate (20 mL), the layers were separated, and the organic layer was washed with aqueous hydrochloric acid (1 N) solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to provide the title compound as an orange-brown semisolid.
1H NMR (CDCl3): δ 7.18-7.25 (m, 2H), 7.04 (m, IH), 3.89 (s, 3H), 2.14 (s, 3H).
Step C Preparation of 4-(2-chloro-4-fluorophenyl)-5-[(2,4-difluorophenyl)methyl]-
1 ,3-dimethyl- lH-pyrazole To a stirred mixture of 5-bromo-4-(2-chloro-4-fluorophenyl)-l,3-dimethyl-lH- pyrazole (i.e. the product of Step B) (0.20 g, 0.66 mmol) in tetrahydrofuran (3 mL) was added dichlorobis(triphenylphosphine)palladium(II) (23 mg, 0.033 mmol) and a solution of 2,4-difluorobenzylzinc chloride (0.5 M in tetrahydrofuran, 2.64 mL, 1.32 mmol). The reaction mixture was heated at reflux for 3 h and then cooled to room temperature and aqueous hydrochloric acid solution (1 N, 3 rnL) was added. The aqueous mixture was extracted with ethyl acetate (20 mL), and the organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to provide an oily material. The oily material was purified by silica gel (5 g) column chromatography (3 to 100% ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a yellow oil (118 mg). 1H NMR (CDCl3): δ 7.18 (m, IH), 7.10 (m, IH), 6.96 (m, IH), 6.80-6.65 (m, 3H), 3.83 (s, 2H), 3.70 (s, 3H), 2.11 (s, 3H).
EXAMPLE 42 Preparation of 4-chloro-l-(4-chlorophenyl)-5-(2,4-difluorophenyl)-lH-l,2,3-triazole
(Compound 24) Step A: Preparation of l-azido-4-chlorobenzene
A stirred mixture of/?-chloroaniline (1.0 g, 7.8 mmol) in trifluoroacetic acid (20 mL) was cooled to 0 0C, and then a solution of sodium nitrite (2.7 g, 39.2 mmol) in water (10 mL) was added over 10 minutes. While maintaining the temperature of the reaction mixture at 0 0C, a solution of sodium azide (5.1 g, 78.4 mmol) in water (10 mL) was added t over 10 minutes. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was extracted with dichloromethane (2x), and the combined organic layers were washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound as a brown oil (1.13 g). 1H NMR (CDCl3): δ 7.31 (m, 2H), 6.96 (m, 2H).
Step B Preparation of 4-chloro-l-(4-chlorophenyl)-5-(2,4-difluorophenyl)-lH-l,2,3- triazole To a mixture of ethylmagnesium chloride (2 M in tetrahydrofuran, 1.2 mL, 2.39 mmol) was added a solution of l-ethynyl-2,4-difluorobenzene (0.300 g, 2.17 mmol) in tetrahydrofuran (1 mL). The reaction mixture was heated at 50 0C for 15 minutes and then allowed to cool to room temperature. A solution of l-azido-4-chlorobenzene (i.e. the product of Step A) (0.328 g, 2.39 mmol) in tetrahydrofuran (1 mL) was added to the reaction mixture, followed by heating at 50 0C. After 1 h, hexachloroethane (1.03 g, 4.34 mmol) was added to the reaction mixture. After 2 h, the reaction mixture was allowed to cool to room temperature, and hydrochloric acid (2 M in diethyl ether, 2 mL) was added. The reaction mixture was concentrated under reduced pressure, and the resulting material was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.35 g). 1H NMR (CDCl3): δ 7.40 (m, 2H), 7.36 (m, IH), 7.26 (m, 2H), 7.03 (m, IH), 6.89 (m, IH). EXAMPLE 43 Preparation of 4-[4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH-l-yl]phenyl thiocyanate (Compound 741)
A mixture of 4-chloro-l-(4-iodophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl- lH-imidazole (prepared by a procedure analogous to Example 13) (0.2 g, 0.43 mmol), cuprous thiocyanate (0.08 g, 0.65 mmol) and potassium thiocyanate (0.06 g, 0.65 mmol) in N,Λ/-dimethylformamide (5 mL) was heated to 140 0C overnight. The reaction mixture was cooled to room temperature and then partitioned between water and ethyl acetate, the layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by medium pressure liquid chromatography on silica gel (20:80 to 60:40 to 80:20 gradient of ethyl acetate in hexane as eluant) to provide the title compound, a compound of the present invention, as solid (0.07 g). 1H NMR (CDCl3): δ 7.53 (d, 2H), 7.22 (d, 2H), 6.40 (d, 2H), 3.78 (s, 3H), 2.31 (s, 3H). By the procedures described herein together with methods known in the art, the following compounds of Tables 1 to 12 can be prepared. The following abbreviations are used in the Tables which follow: Me means methyl, Et means ethyl, Ph means phenyl, MeO means methoxy, MeS is methylthio, CN means cyano, Bn means benzyl and NO2 means nitro. Table 1
Figure imgf000087_0001
Q2 is 4-Cl-Ph, R2 is Cl and R4 is Me.
Figure imgf000087_0003
Figure imgf000087_0002
Figure imgf000087_0004
Q2 is 4-Cl-Ph, R2 is Cl and R4 is Me.
(R5a} (R5a} (R5a} (R5a}
'm 'm 'm 'm (R5a> m
2-Cl, 3,6-di-F 2-Cl, 6-F, 5-MeO 2,6-di-F, 3-CF2HO 2,6-di-F, 3-EtO
The present disclosure also includes Tables IA through 934A, each of which is constructed the same as Table 1 above except that the row heading in Table 1 (i.e. "Q2 is 4-Cl-Ph, R2 is Cl and R4 is Me") is replaced with the respective row heading shown below. For example, in Table IA the row heading is "Q2 is 4-Cl-Ph, R2 is Br and R4 is Me", and (R5a)m is as defined in Table 1 above. Thus, the first entry in Table IA specifically discloses 4-bromo-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole. Tables 2A through 934A are constructed similarly.
Table Row Heading
IA Q2 is 4-Cl-Ph, R2 is Br and R4 is Me.
2A Q2 is 4-Cl-Ph, R2 is Cl and R4 is CFH2.
3A Q2 is 4-Cl-Ph, R2 is I and R4 is Me.
4A Q2 is 4-Cl-Ph, R2 is Me and R4 is Me.
5A Q2 is 4-Cl-Ph, R2 is Me and R4 is Cl.
6A Q2 is 4-Cl-Ph, R2 is Me and R4 is Br.
7A Q2 is 4-Cl-Ph, R2 is Me and R4 is I.
8A Q2 is 4-Cl-Ph, R2 is Me and R4 is MeO.
9A Q2 is 4-Cl-Ph, R2 is MeO and R4 is Me.
1OA Q2 is 4-Cl-Ph, R2 is Br and R4 is Br.
HA Q2 is 4-Cl-Ph, R2 is Br and R4 is Cl.
12A Q2 is 4-Cl-Ph, R2 is Cl and R4 is Br.
13A Q2 is 4-Cl-Ph, R2 is Cl and R4 is Cl.
14A Q2 is 4-Cl-Ph, R2 is Me and R4 is MeS.
15A Q2 is 4-Cl-Ph, R2 is MeS and R4 is Me.
16A Q2 is 4-Cl-Ph, R2 is Et and R4 is Br.
17A Q2 is 4-Cl-Ph, R2 is Et and R4 is Cl.
18A Q2 is 4-Cl-Ph, R2 is Et and R4 is Me.
19A Q2 is 4-Cl-Ph, R2 is Me and R4 is Et.
2OA Q2 is 4-Cl-Ph, R2 is Cl and R4 is Et.
21A Q2 is 4-Cl-Ph, R2 is Me and R4 is CN.
22A Q2 is 4-Cl-Ph, R2 is Me and R4 is H.
23A Q2 is 4-Cl-Ph, R2 is Cl and R4 is H.
24A Q2 is 4-Cl-Ph, R2 is Br and R4 is H.
25A Q2 is 3 -Cl-Ph, R2 is Cl and R4 is Me.
26A Q2 is 3 -Cl-Ph, R2 is Cl and R4 is CFH2. Table Row Heading
27A Q2 is 3 -Cl-Ph, R2 is Br and R4 is Me.
28A Q2 is 3 -Cl-Ph, R2 is I and R4 is Me.
29A Q2 is 3 -Cl-Ph, R2 is Me and R4 is Me.
3OA Q2 is 3 -Cl-Ph, R2 is Me and R4 is Cl.
3 IA Q2 is 3 -Cl-Ph, R2 is Me and R4 is Br.
32A Q2 is 3 -Cl-Ph, R2 is Me and R4 is I.
33A Q2 is 3 -Cl-Ph, R2 is Br and R4 is Br.
34A Q2 is 3 -Cl-Ph, R2 is Br and R4 is Cl.
35A Q2 is 3 -Cl-Ph, R2 is Cl and R4 is Br.
36A Q2 is 3 -Cl-Ph, R2 is Cl and R4 is Cl.
37A Q2 is 3 -Cl-Ph, R2 is Me and R4 is H.
38A Q2 is 3 -Cl-Ph, R2 is Cl and R4 is H.
39A Q2 is 3 -Cl-Ph, R2 is Br and R4 is H
4OA Q2 is 4-F-Ph, R2 is Cl and R4 is Me.
41A Q2 is 4-F-Ph, R2 is Cl and R4 is CFH2.
42A Q2 is 4-F-Ph, R2 is Br and R4 is Me.
43A Q2 is 4-F-Ph, R2 is I and R4 is Me.
44A Q2 is 4-F-Ph, R2 is Me and R4 is Me.
45A Q2 is 4-F-Ph, R2 is Me and R4 is Cl.
46A Q2 is 4-F-Ph, R2 is Me and R4 is Br.
47A Q2 is 4-F-Ph, R2 is Me and R4 is I.
48A Q2 is 4-F-Ph, R2 is Br and R4 is Br.
49A Q2 is 4-F-Ph, R2 is Br and R4 is Cl.
5OA Q2 is 4-F-Ph, R2 is Cl and R4 is Br.
5 IA Q2 is 4-F-Ph, R2 is Cl and R4 is Cl.
52A Q2 is 4-F-Ph, R2 is Me and R4 is H.
53A Q2 is 4-F-Ph, R2 is Cl and R4 is H.
54A Q2 is 4-F-Ph, R2 is Br and R4 is H.
55A Q2 is 3-F-Ph, R2 is Cl and R4 is Me.
56A Q2 is 3-F-Ph, R2 is Cl and R4 is CFH2.
57A Q2 is 3-F-Ph, R2 is Br and R4 is Me.
58A Q2 is 3-F-Ph, R2 is I and R4 is Me.
59A Q2 is 3-F-Ph, R2 is Me and R4 is Me.
6OA Q2 is 3-F-Ph, R2 is Me and R4 is Cl.
61A Q2 is 3-F-Ph, R2 is Me and R4 is Br.
62A Q2 is 3-F-Ph, R2 is Me and R4 is I.
63A Q2 is 3-F-Ph, R2 is Br and R4 is Br. Table Row Heading
64A Q2 is 3-F-Ph, R2 is Br and R4 is Cl.
65A Q2 is 3-F-Ph, R2 is Cl and R4 is Br.
66A Q2 is 3-F-Ph, R2 is Cl and R4 is Cl.
67A Q2 is 3-F-Ph, R2 is Me and R4 is H.
68A Q2 is 3-F-Ph, R2 is Cl and R4 is H.
69A Q2 is 3-F-Ph, R2 is Br and R4 is H
7OA Q2 is 3-CF2HO-Ph, R2 is Cl and R4 is Me.
71A Q2 is 3-CF2HO-Ph, R2 is Cl and R4 is CFH2
72A Q2 is 3-CF2HO-Ph, R2 is Br and R4 is Me.
73A Q2 is 3-CF2HO-Ph, R2 is I and R4 is Me.
74A Q2 is 3-CF2HO-Ph, R2 is Me and R4 is Me.
75A Q2 is 3-CF2HO-Ph, R2 is Me and R4 is Cl.
76A Q2 is 3-CF2HO-Ph, R2 is Me and R4 is Br.
77A Q2 is 3-CF2HO-Ph, R2 is Me and R4 is I.
78A Q2 is 3-CF2HO-Ph, R2 is Br and R4 is Br.
79A Q2 is 3-CF2HO-Ph, R2 is Br and R4 is Cl.
8OA Q2 is 3-CF2HO-Ph, R2 is Cl and R4 is Br.
81A Q2 is 3-CF2HO-Ph, R2 is Cl and R4 is Cl.
82A Q2 is 3-CF2HO-Ph, R2 is Me and R4 is H.
83A Q2 is 3-CF2HO-Ph, R2 is Cl and R4 is H.
84A Q2 is 3-CF2HO-Ph, R2 is Br and R4 is H
85A Q2 is 4-Me-Ph, R2 is Cl and R4 is Me.
86A Q2 is 4-Me-Ph, R2 is Cl and R4 is CFH2.
87A Q2 is 4-Me-Ph, R2 is Br and R4 is Me.
88A Q2 is 4-Me-Ph, R2 is I and R4 is Me.
89A Q2 is 4-Me-Ph, R2 is Me and R4 is Me.
9OA Q2 is 4-Me-Ph, R2 is Me and R4 is Cl.
91A Q2 is 4-Me-Ph, R2 is Me and R4 is Br.
92A Q2 is 4-Me-Ph, R2 is Me and R4 is I.
93A Q2 is 4-Me-Ph, R2 is Br and R4 is Br.
94A Q2 is 4-Me-Ph, R2 is Br and R4 is Cl.
95A Q2 is 4-Me-Ph, R2 is Cl and R4 is Br.
96A Q2 is 4-Me-Ph, R2 is Cl and R4 is Cl.
97A Q2 is 4-Me-Ph, R2 is Me and R4 is H.
98A Q2 is 4-Me-Ph, R2 is Cl and R4 is H.
99A Q2 is 4-Me-Ph, R2 is Br and R4 is H.
IOOA Q2 is 3-Me-Ph, R2 is Cl and R4 is Me. Table Row Heading
101A Q2 is 3-Me-Ph, R2 is Cl and R4 is CFH2.
102A Q2 is 3-Me-Ph, R2 is Br and R4 is Me.
103A Q2 is 3-Me-Ph, R2 is I and R4 is Me.
104A Q2 is 3-Me-Ph, R2 is Me and R4 is Me.
105 A Q2 is 3-Me-Ph, R2 is Me and R4 is Cl.
106A Q2 is 3-Me-Ph, R2 is Me and R4 is Br.
107A Q2 is 3-Me-Ph, R2 is Me and R4 is I.
108A Q2 is 3-Me-Ph, R2 is Br and R4 is Br.
109A Q2 is 3-Me-Ph, R2 is Br and R4 is Cl.
HOA Q2 is 3-Me-Ph, R2 is Cl and R4 is Br.
H iA Q2 is 3-Me-Ph, R2 is Cl and R4 is Cl.
112A Q2 is 3-Me-Ph, R2 is Me and R4 is H.
113A Q2 is 3-Me-Ph, R2 is Cl and R4 is H.
114A Q2 is 3-Me-Ph, R2 is Br and R4 is H.
115A Q2 is 4-Et-Ph, R2 is Cl and R4 is Me.
116A Q2 is 4-Et-Ph, R2 is Cl and R4 is CFH2.
117A Q2 is 4-Et-Ph, R2 is Br and R4 is Me.
118A Q2 is 4-Et-Ph, R2 is I and R4 is Me.
119A Q2 is 4-Et-Ph, R2 is Me and R4 is Me.
120A Q2 is 4-Et-Ph, R2 is Me and R4 is Cl.
121A Q2 is 4-Et-Ph, R2 is Me and R4 is Br.
122 A Q2 is 4-Et-Ph, R2 is Me and R4 is I.
123A Q2 is 4-Et-Ph, R2 is Br and R4 is Br.
124A Q2 is 4-Et-Ph, R2 is Br and R4 is Cl.
125A Q2 is 4-Et-Ph, R2 is Cl and R4 is Br.
126A Q2 is 4-Et-Ph, R2 is Cl and R4 is Cl.
127A Q2 is 4-Et-Ph, R2 is Me and R4 is H.
128A Q2 is 4-Et-Ph, R2 is Cl and R4 is H.
129 A Q2 is 4-Et-Ph, R2 is Br and R4 is H.
13OA Q2 is 4-Cl, 3-F-Ph, R2 is Cl and R4 is Me.
131A Q2 is 4-Cl, 3-F-Ph, R2 is Cl and R4 is CFH2.
132A Q2 is 4-Cl, 3-F-Ph, R2 is Br and R4 is Me.
133A Q2 is 4-Cl, 3-F-Ph, R2 is I and R4 is Me.
134A Q2 is 4-Cl, 3-F-Ph, R2 is Me and R4 is Me.
135A Q2 is 4-Cl, 3-F-Ph, R2 is Me and R4 is Cl.
136A Q2 is 4-Cl, 3-F-Ph, R2 is Me and R4 is Br.
137A Q2 is 4-Cl, 3-F-Ph, R2 is Me and R4 is I. Table Row Heading
138A Q2 is 4-Cl, 3-F-Ph, R2 is Br and R4 is Br.
139A Q2 is 4-Cl, 3-F-Ph, R2 is Br and R4 is Cl.
140A Q2 is 4-Cl, 3-F-Ph, R2 is Cl and R4 is Br.
141A Q2 is 4-Cl, 3-F-Ph, R2 is Cl and R4 is Cl.
142 A Q2 is 4-Cl, 3-F-Ph, R2 is Me and R4 is H.
143A Q2 is 4-Cl, 3-F-Ph R2 is Cl and R4 is H.
144A Q2 is 4-Cl, 3-F-Ph, R2 is Br and R4 is H.
145 A Q2 is 2-Cl, 4-F-Ph, R2 is Cl and R4 is Me.
146A Q2 is 2-Cl, 4-F-Ph, R2 is Cl and R4 is CFH2.
147 A Q2 is 2-Cl, 4-F-Ph, R2 is Br and R4 is Me.
148A Q2 is 2-Cl, 4-F-Ph, R2 is I and R4 is Me.
149 A Q2 is 2-Cl, 4-F-Ph, R2 is Me and R4 is Me.
150A Q2 is 2-Cl, 4-F-Ph, R2 is Me and R4 is Cl.
151A Q2 is 2-Cl, 4-F-Ph, R2 is Me and R4 is Br.
152A Q2 is 2-Cl, 4-F-Ph, R2 is Me and R4 is I.
153A Q2 is 2-Cl, 4-F-Ph, R2 is Br and R4 is Br.
154A Q2 is 2-Cl, 4-F-Ph, R2 is Br and R4 is Cl.
155A Q2 is 2-Cl, 4-F-Ph, R2 is Cl and R4 is Br.
156A Q2 is 2-Cl, 4-F-Ph, R2 is Cl and R4 is Cl.
157A Q2 is 2-Cl, 4-F-Ph, R2 is Me and R4 is H.
158A Q2 is 2-Cl, 4-F-Ph R2 is Cl and R4 is H.
159A Q2 is 2-Cl, 4-F-Ph, R2 is Br and R4 is H.
160A Q2 is 4-F, 3-Me-Ph, R2 is Cl and R4 is Me.
161A Q2 is 4-F, 3-Me-Ph, R2 is Cl and R4 is CFH2.
162 A Q2 is 4-F, 3-Me-Ph, R2 is Br and R4 is Me.
163 A Q2 is 4-F, 3-Me-Ph, R2 is I and R4 is Me.
164A Q2 is 4-F, 3-Me-Ph, R2 is Me and R4 is Me.
165 A Q2 is 4-F, 3-Me-Ph, R2 is Me and R4 is Cl.
166A Q2 is 4-F, 3-Me-Ph, R2 is Me and R4 is Br.
167A Q2 is 4-F, 3-Me-Ph, R2 is Me and R4 is I.
168A Q2 is 4-F, 3-Me-Ph, R2 is Br and R4 is Br.
169 A Q2 is 4-F, 3-Me-Ph, R2 is Br and R4 is Cl.
170A Q2 is 4-F, 3-Me-Ph, R2 is Cl and R4 is Br.
171A Q2 is 4-F, 3-Me-Ph, R2 is Cl and R4 is Cl.
172A Q2 is 4-F, 3-Me-Ph, R2 is Me and R4 is H.
173A Q2 is 4-F, 3-Me-Ph, R2 is Cl and R4 is H.
174A Q2 is 4-F, 3-Me-Ph, R2 is Br and R4 is H. Table Row Heading
175 A Q2 is 3,4-di-F-Ph, R2 is Cl and R4 is Me.
176A Q2 is 3,4-di-F-Ph, R2 is Cl and R4 is CFH2.
177A Q2 is 3,4-di-F-Ph, R2 is Br and R4 is Me.
178A Q2 is 3,4-di-F-Ph, R2 is I and R4 is Me.
179A Q2 is 3,4-di-F-Ph, R2 is Me and R4 is Me.
180A Q2 is 3,4-di-F-Ph, R2 is Me and R4 is Cl.
181A Q2 is 3,4-di-F-Ph, R2 is Me and R4 is Br.
182A Q2 is 3,4-di-F-Ph, R2 is Me and R4 is I.
183 A Q2 is 3,4-di-F-Ph, R2 is Br and R4 is Br.
184A Q2 is 3,4-di-F-Ph, R2 is Br and R4 is Cl.
185A Q2 is 3,4-di-F-Ph, R2 is Cl and R4 is Br.
186A Q2 is 3,4-di-F-Ph, R2 is Cl and R4 is Cl.
187A Q2 is 3,4-di-F-Ph, R2 is Me and R4 is H.
188A Q2 is 3,4-di-F-Ph, R2 is Cl and R4 is H.
189A Q2 is 3,4-di-F-Ph, R2 is Br and R4 is H.
190A Q2 is 3,4-di-Cl-Ph, R2 is Cl and R4 is Me.
191A Q2 is 3,4-di-Cl-Ph, R2 is Cl and R4 is CFH2.
192 A Q2 is 3,4-di-Cl-Ph, R2 is Br and R4 is Me.
193A Q2 is 3,4-di-Cl-Ph, R2 is I and R4 is Me.
194A Q2 is 3,4-di-Cl-Ph, R2 is Me and R4 is Me.
195A Q2 is 3,4-di-Cl-Ph, R2 is Me and R4 is Cl.
196A Q2 is 3,4-di-Cl-Ph, R2 is Me and R4 is Br.
197A Q2 is 3,4-di-Cl-Ph, R2 is Me and R4 is I.
198A Q2 is 3,4-di-Cl-Ph, R2 is Br and R4 is Br.
199 A Q2 is 3,4-di-Cl-Ph, R2 is Br and R4 is Cl.
200A Q2 is 3,4-di-Cl-Ph, R2 is Cl and R4 is Br.
201A Q2 is 3,4-di-Cl-Ph, R2 is Cl and R4 is Cl.
202A Q2 is 3,4-di-Cl-Ph, R2 is Me and R4 is H.
203A Q2 is 3,4-di-Cl-Ph, R2 is Cl and R4 is H.
204A Q2 is 3,4-di-Cl-Ph, R2 is Br and R4 is H.
205A Q2 is 3,5-di-MeO-Ph, R2 is Cl and R4 is Me.
206A Q2 is 3,5-di-MeO-Ph, R2 is Cl and R4 is CFH2.
207A Q2 is 3,5-di-MeO-Ph, R2 is Br and R4 is Me.
208A Q2 is 3,5-di-MeO-Ph, R2 is I and R4 is Me.
209A Q2 is 3,5-di-MeO-Ph, R2 is Me and R4 is Me.
210A Q2 is 3,5-di-MeO-Ph, R2 is Me and R4 is Cl.
211A Q2 is 3,5-di-MeO-Ph, R2 is Me and R4 is Br. Table Row Heading
212A Q2 is 3,5-di-MeO-Ph, R2 is Mt ; and R4 is I.
213A Q2 is 3,5-di-MeO-Ph, R2 is Br and R4 is Br.
214A Q2 is 3,5-di-MeO-Ph, R2 is Br and R4 is Cl.
215A Q2 is 3,5-di-MeO-Ph, R2 is Cl and R4 is Br.
216A Q2 is 3,5-di-MeO-Ph, R2 is Cl and R4 is Cl.
217A Q2 is 3,5-di-MeO-Ph, R2 is Mt ; and R4 is H.
218A Q2 is 3,5-di-MeO-Ph, R2 is Cl and R4 is H.
219A Q2 is 3,5-di-MeO-Ph, R2 is Br and R4 is H.
220A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is Me.
221A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is CFH2.
222A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is Me.
223A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is I and R4 is Me.
224A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is Me.
225A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is Cl.
226A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is Br.
227A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is I.
228A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is Br.
229A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is Cl.
230A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is Br.
23 IA Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is Cl.
232A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is H.
233A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is H.
234A Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is H.
235A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is Me.
236A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is CFH2.
237A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is Me.
238A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is I and R4 is Me.
239A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is Me.
240A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is Cl.
241A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is Br.
242A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is I.
243A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is Br.
244A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is Cl.
245A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is Br.
246A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is Cl.
247A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is H.
248A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is H. Table Row Heading
249A Q2 is 4-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is H.
250A Q2 is 4-Cl-Bn, R2 is Cl and R4 is Me.
251A Q2 is 4-Cl-Bn, R2 is Cl and R4 is CFH2.
252A Q2 is 4-Cl-Bn, R2 is Br and R4 is Me.
253A Q2 is 4-Cl-Bn, R2 is I and R4 is Me.
254A Q2 is 4-Cl-Bn, R2 is Me and R4 is Me.
255A Q2 is 4-Cl-Bn, R2 is Me and R4 is Cl.
256A Q2 is 4-Cl-Bn, R2 is Me and R4 is Br.
257A Q2 is 4-Cl-Bn, R2 is Me and R4 is I.
258A Q2 is 4-Cl-Bn, R2 is Br and R4 is Br.
259A Q2 is 4-Cl-Bn, R2 is Br and R4 is Cl.
260A Q2 is 4-Cl-Bn, R2 is Cl and R4 is Br.
261A Q2 is 4-Cl-Bn, R2 is Cl and R4 is Cl.
262A Q2 is 4-Cl-Bn, R2 is Me and R4 is H.
263A Q2 is 4-Cl-Bn, R2 is Cl and R4 is H.
264A Q2 is 4-Cl-Bn, R2 is Br and R4 is H.
265A Q2 is 4-F-Bn, R2 is Cl and R4 is Me.
266A Q2 is 4-F-Bn, R2 is Cl and R4 is CFH2.
267A Q2 is 4-F-Bn, R2 is Br and R4 is Me.
268A Q2 is 4-F-Bn, R2 is I and R4 is Me.
269A Q2 is 4-F-Bn, R2 is Me and R4 is Me.
270A Q2 is 4-F-Bn, R2 is Me and R4 is Cl.
271A Q2 is 4-F-Bn, R2 is Me and R4 is Br.
272A Q2 is 4-F-Bn, R2 is Me and R4 is I.
273A Q2 is 4-F-Bn, R2 is Br and R4 is Br.
274A Q2 is 4-F-Bn, R2 is Br and R4 is Cl.
275A Q2 is 4-F-Bn, R2 is Cl and R4 is Br.
276A Q2 is 4-F-Bn, R2 is Cl and R4 is Cl.
277A Q2 is 4-F-Bn, R2 is Me and R4 is H.
278A Q2 is 4-F-Bn, R2 is Cl and R4 is H.
279A Q2 is 4-F-Bn, R2 is Br and R4 is H.
280A Q2 is 6-Cl-3-pyridinyl, R2 is Cl and R4 is Me.
281A Q2 is 6-Cl-3-pyridinyl, R2 is Cl and R4 is CFH2.
282A Q2 is 6-Cl-3-pyridinyl, R2 is Br and R4 is Me.
283A Q2 is 6-Cl-3-pyridinyl, R2 is I and R4 is Me.
284A Q2 is 6-Cl-3-pyridinyl, R2 is Me and R4 is Me.
285A Q2 is 6-Cl-3-pyridinyl, R2 is Me and R4 is Cl. Table Row Heading
286A Q2 is 6-Cl-3-pyridinyl, R2 is Me and R4 is Br.
287A Q2 is 6-Cl-3-pyridinyl, R2 is Me and R4 is I.
288A Q2 is 6-Cl-3-pyridinyl, R2 is Me and R4 is MeO.
289A Q2 is 6-Cl-3-pyridinyl, R2 is MeO and R4 is Me.
290A Q2 is 6-Cl-3-pyridinyl, R2 is Br and R4 is Br.
291A Q2 is 6-Cl-3-pyridinyl, R2 is Br and R4 is Cl.
292A Q2 is 6-Cl-3-pyridinyl, R2 is Cl and R4 is Br.
293A Q2 is 6-Cl-3-pyridinyl, R2 is Cl and R4 is Cl.
294A Q2 is 6-Cl-3-pyridinyl, R2 is Me and R4 is MeS.
295A Q2 is 6-Cl-3-pyridinyl, R2 is MeS and R4 is Me.
296A Q2 is 6-Cl-3-pyridinyl, R2 is Et and R4 is Br.
297A Q2 is 6-Cl-3-pyridinyl, R2 is Et and R4 is Cl.
298A Q2 is 6-Cl-3-pyridinyl, R2 is Et and R4 is Me.
299A Q2 is 6-Cl-3-pyridinyl, R2 is Me and R4 is Et.
300A Q2 is 6-Cl-3-pyridinyl, R2 is Cl and R4 is Et.
301A Q2 is 6-Cl-3-pyridinyl, R2 is Me and R4 is CN.
302 A Q2 is 6-Cl-3-pyridinyl, R2 is Me and R4 is H.
303A Q2 is 6-Cl-3-pyridinyl, R2 is Cl and R4 is H.
304A Q2 is 6-Cl-3-pyridinyl, R2 is Br and R4 is H.
305A Q2 is 6-Me-3-pyridinyl, R2 is Cl and R4 is Me.
306A Q2 is 6-Me-3-pyridinyl, R2 is Cl and R4 is CFH2.
307A Q2 is 6-Me-3-pyridinyl, R2 is Br and R4 is Me.
308A Q2 is 6-Me-3-pyridinyl, R2 is I and R4 is Me.
309 A Q2 is 6-Me-3-pyridinyl, R2 is Me and R4 is Me.
310A Q2 is 6-Me-3-pyridinyl, R2 is Me and R4 is Cl.
311A Q2 is 6-Me-3-pyridinyl, R2 is Me and R4 is Br.
312A Q2 is 6-Me-3-pyridinyl, R2 is Me and R4 is I.
313A Q2 is 6-Me-3-pyridinyl, R2 is Br and R4 is Br.
314A Q2 is 6-Me-3-pyridinyl, R2 is Br and R4 is Cl.
315A Q2 is 6-Me-3-pyridinyl, R2 is Cl and R4 is Br.
316A Q2 is 6-Me-3-pyridinyl, R2 is Cl and R4 is Cl.
317A Q2 is 6-Me-3-pyridinyl, R2 is Me and R4 is H.
318A Q2 is 6-Me-3-pyridinyl, R2 is Cl and R4 is H.
319A Q2 is 6-Me-3-pyridinyl, R2 is Br and R4 is H.
320A Q2 is 6-MeO-3-pyridinyl, R2 is Cl and R4 is Me.
321A Q2 is 6-MeO-3-pyridinyl, R2 is Cl and R4 is CFH2.
322A Q2 is 6-MeO-3-pyridinyl, R2 is Br and R4 is Me. Table Row Heading
323A Q2 is 6-MeO-3-pyridinyl, R2 is I and R4 is Me.
324A Q2 is 6-MeO-3-pyridinyl, R2 is Me and R4 is Me.
325A Q2 is 6-MeO-3-pyridinyl, R2 is Me and R4 is Cl.
326A Q2 is 6-MeO-3-pyridinyl, R2 is Me and R4 is Br.
327A Q2 is 6-MeO-3-pyridinyl, R2 is Me and R4 is I.
328A Q2 is 6-MeO-3-pyridinyl, R2 is Br and R4 is Br.
329A Q2 is 6-MeO-3-pyridinyl, R2 is Br and R4 is Cl.
330A Q2 is 6-MeO-3-pyridinyl, R2 is Cl and R4 is Br.
331A Q2 is 6-MeO-3-pyridinyl, R2 is Cl and R4 is Cl.
332A Q2 is 6-MeO-3-pyridinyl, R2 is Me and R4 is H.
333A Q2 is 6-MeO-3-pyridinyl, R2 is Cl and R4 is H.
334A Q2 is 6-MeO-3-pyridinyl, R2 is Br and R4 is H.
335A Q2 is 6-CF3-3-pyridinyl, R2 is Cl and R4 is Me.
336A Q2 is 6-CF3-3-pyridinyl, R2 is Cl and R4 is CFH2.
337A Q2 is 6-CF3-3-pyridinyl, R2 is Br and R4 is Me.
338A Q2 is 6-CF3-3-pyridinyl, R2 is I and R4 is Me.
339A Q2 is 6-CF3-3-pyridinyl, R2 is Me and R4 is Me.
340A Q2 is 6-CF3-3-pyridinyl, R2 is Me and R4 is Cl.
341A Q2 is 6-CF3-3-pyridinyl, R2 is Me and R4 is Br.
342A Q2 is 6-CF3-3-pyridinyl, R2 is Me and R4 is I.
343A Q2 is 6-CF3-3-pyridinyl, R2 is Br and R4 is Br.
344A Q2 is 6-CF3-3-pyridinyl, R2 is Br and R4 is Cl.
345A Q2 is 6-CF3-3-pyridinyl, R2 is Cl and R4 is Br.
346A Q2 is 6-CF3-3-pyridinyl, R2 is Cl and R4 is Cl.
347A Q2 is 6-CF3-3-pyridinyl, R2 is Me and R4 is H.
348A Q2 is 6-CF3-3-pyridinyl, R2 is Cl and R4 is H.
349A Q2 is 6-CF3-3-pyridinyl, R2 is Br and R4 is H.
350A Q2 is 6-Br-3-pyridinyl, R2 is Cl and R4 is Me.
351A Q2 is 6-Br-3-pyridinyl, R2 is Cl and R4 is CFH2.
352A Q2 is 6-Br-3-pyridinyl, R2 is Br and R4 is Me.
353A Q2 is 6-Br-3-pyridinyl, R2 is I and R4 is Me.
354A Q2 is 6-Br-3-pyridinyl, R2 is Me and R4 is Me.
355A Q2 is 6-Br-3-pyridinyl, R2 is Me and R4 is Cl.
356A Q2 is 6-Br-3-pyridinyl, R2 is Me and R4 is Br.
357A Q2 is 6-Br-3-pyridinyl, R2 is Me and R4 is I.
358A Q2 is 6-Br-3-pyridinyl, R2 is Br and R4 is Br.
359A Q2 is 6-Br-3-pyridinyl, R2 is Br and R4 is Cl. Table Row Heading
360A Q2 is 6-Br-3-pyridinyl, R2 is Cl and R4 is Br.
361A Q2 is 6-Br-3-pyridinyl, R2 is Cl and R4 is Cl.
362 A Q2 is 6-Br-3-pyridinyl, R2 is Me and R4 is H.
363A Q2 is 6-Br-3-pyridinyl, R2 is Cl and R4 is H.
364A Q2 is 6-Br-3-pyridinyl, R2 is Br and R4 is H.
365 A Q2 is 6-F-3-pyridinyl, R2 is Cl and R4 is Me.
366A Q2 is 6-F-3-pyridinyl, R2 is Cl and R4 is CFH2.
367 A Q2 is 6-F-3-pyridinyl, R2 is Br and R4 is Me.
368A Q2 is 6-F-3-pyridinyl, R2 is I and R4 is Me.
369 A Q2 is 6-F-3-pyridinyl, R2 is Me and R4 is Me.
370A Q2 is 6-F-3-pyridinyl, R2 is Me and R4 is Cl.
371A Q2 is 6-F-3-pyridinyl, R2 is Me and R4 is Br.
372 A Q2 is 6-F-3-pyridinyl, R2 is Me and R4 is I.
373A Q2 is 6-F-3-pyridinyl, R2 is Br and R4 is Br.
374A Q2 is 6-F-3-pyridinyl, R2 is Br and R4 is Cl.
375A Q2 is 6-F-3-pyridinyl, R2 is Cl and R4 is Br.
376A Q2 is 6-F-3-pyridinyl, R2 is Cl and R4 is Cl.
377A Q2 is 6-F-3-pyridinyl, R2 is Me and R4 is H.
378A Q2 is 6-F-3-pyridinyl, R2 is Cl and R4 is H.
379 A Q2 is 6-F-3-pyridinyl, R2 is Br and R4 is H.
380A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Cl and R4 is Me.
381A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Cl and R4 is CFH2.
382A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Br and R4 is Me.
383A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is I and R4 is Me.
384A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Me and R4 is Me.
385 A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Me and R4 is Cl.
386A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Me and R4 is Br.
387A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Me and R4 is I.
388A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Br and R4 is Br.
389A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Br and R4 is Cl.
390A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Cl and R4 is Br.
391A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Cl and R4 is Cl.
392A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Me and R4 is H.
393A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Cl and R4 is H.
394A Q2 is 2-Cl, 6-Me-4-pyridinyl, R2 is Br and R4 is H.
395A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Cl and R4 is Me.
396A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Cl and R4 is CFH2. Table Row Heading
397A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Br and R4 is Me.
398A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is I and R4 is Me.
399A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Me and R4 is Me.
400A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Me and R4 is Cl.
401A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Me and R4 is Br.
402A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Me and R4 is I.
403A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Br and R4 is Br.
404A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Br and R4 is Cl.
405A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Cl and R4 is Br.
406A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Cl and R4 is Cl.
407A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Me and R4 is H.
408A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Cl and R4 is H.
409A Q2 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Br and R4 is H.
410A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Cl and R4 is Me.
411A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Cl and R4 is CFH2.
412A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Br and R4 is Me.
413A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is I and R4 is Me.
414A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Me and R4 is Me.
415A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Me and R4 is Cl.
416A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Me and R4 is Br.
417A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Me and R4 is I.
418A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Br and R4 is Br.
419A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Br and R4 is Cl.
420A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Cl and R4 is Br.
42 IA Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Cl and R4 is Cl.
422A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Me and R4 is H.
423A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Cl and R4 is H.
424A Q2 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Br and R4 is H.
425A Q2 is 5-Cl-3-pyridinyl, R2 is Cl and R4 is Me.
426A Q2 is 5-Cl-3-pyridinyl, R2 is Cl and R4 is CFH2.
427A Q2 is 5-Cl-3-pyridinyl, R2 is Br and R4 is Me.
428A Q2 is 5-Cl-3-pyridinyl, R2 is I and R4 is Me.
429A Q2 is 5-Cl-3-pyridinyl, R2 is Me and R4 is Me.
430A Q2 is 5-Cl-3-pyridinyl, R2 is Me and R4 is Cl.
43 IA Q2 is 5-Cl-3-pyridinyl, R2 is Me and R4 is Br.
432A Q2 is 5-Cl-3-pyridinyl, R2 is Me and R4 is I.
433A Q2 is 5-Cl-3-pyridinyl, R2 is Br and R4 is Br. Table Row Heading
434A Q2 is 5-Cl-3-pyridinyl, R2 is Br and R4 is Cl.
435 A Q2 is 5-Cl-3-pyridinyl, R2 is Cl and R4 is Br.
436A Q2 is 5-Cl-3-pyridinyl, R2 is Cl and R4 is Cl.
437 A Q2 is 5-Cl-3-pyridinyl, R2 is Me and R4 is H.
438A Q2 is 5-Cl-3-pyridinyl, R2 is Cl and R4 is H.
439A Q2 is 5-Cl-3-pyridinyl, R2 is Br and R4 is H.
440A Q2 is 5-F-3-pyridinyl, R2 is Cl and R4 is Me.
441A Q2 is 5-F-3-pyridinyl, R2 is Cl and R4 is CFH2.
442A Q2 is 5-F-3-pyridinyl, R2 is Br and R4 is Me.
443A Q2 is 5-F-3-pyridinyl, R2 is I and R4 is Me.
444A Q2 is 5-F-3-pyridinyl, R2 is Me and R4 is Me.
445A Q2 is 5-F-3-pyridinyl, R2 is Me and R4 is Cl.
446A Q2 is 5-F-3-pyridinyl, R2 is Me and R4 is Br.
447A Q2 is 5-F-3-pyridinyl, R2 is Me and R4 is I.
448A Q2 is 5-F-3-pyridinyl, R2 is Br and R4 is Br.
449A Q2 is 5-F-3-pyridinyl, R2 is Br and R4 is Cl.
450A Q2 is 5-F-3-pyridinyl, R2 is Cl and R4 is Br.
45 IA Q2 is 5-F-3-pyridinyl, R2 is Cl and R4 is Cl.
452A Q2 is 5-F-3-pyridinyl, R2 is Me and R4 is H.
453A Q2 is 5-F-3-pyridinyl, R2 is Cl and R4 is H.
454A Q2 is 5-F-3-pyridinyl, R2 is Br and R4 is H.
455A Q2 is 5-Me-3-pyridinyl, R2 is Cl and R4 is Me.
456A Q2 is 5-Me-3-pyridinyl, R2 is Cl and R4 is CFH2.
457A Q2 is 5-Me-3-pyridinyl, R2 is Br and R4 is Me.
458 A Q2 is 5-Me-3-pyridinyl, R2 is I and R4 is Me.
459A Q2 is 5-Me-3-pyridinyl, R2 is Me and R4 is Me.
460A Q2 is 5-Me-3-pyridinyl, R2 is Me and R4 is Cl.
461A Q2 is 5-Me-3-pyridinyl, R2 is Me and R4 is Br.
462A Q2 is 5-Me-3-pyridinyl, R2 is Me and R4 is I.
463A Q2 is 5-Me-3-pyridinyl, R2 is Br and R4 is Br.
464A Q2 is 5-Me-3-pyridinyl, R2 is Br and R4 is Cl.
465A Q2 is 5-Me-3-pyridinyl, R2 is Cl and R4 is Br.
466A Q2 is 5-Me-3-pyridinyl, R2 is Cl and R4 is Cl.
467A Q2 is 5-Me-3-pyridinyl, R2 is Me and R4 is H.
468A Q2 is 5-Me-3-pyridinyl, R2 is Cl and R4 is H.
469A Q2 is 5-Me-3-pyridinyl, R2 is Br and R4 is H.
470A Q2 is 5-MeO-3-pyridinyl, R2 is Cl and R4 is Me. Table Row Heading
471A Q2 is 5-MeO-3-pyridinyl, R2 is Cl and R4 is CFH2.
472A Q2 is 5-MeO-3-pyridinyl, R2 is Br and R4 is Me.
473A Q2 is 5-MeO-3-pyridinyl, R2 is I and R4 is Me.
474A Q2 is 5-MeO-3-pyridinyl, R2 is Me and R4 is Me.
475A Q2 is 5-MeO-3-pyridinyl, R2 is Me and R4 is Cl.
476A Q2 is 5-MeO-3-pyridinyl, R2 is Me and R4 is Br.
477A Q2 is 5-MeO-3-pyridinyl, R2 is Me and R4 is I.
478A Q2 is 5-MeO-3-pyridinyl, R2 is Br and R4 is Br.
479A Q2 is 5-MeO-3-pyridinyl, R2 is Br and R4 is Cl.
480A Q2 is 5-MeO-3-pyridinyl, R2 is Cl and R4 is Br.
481A Q2 is 5-MeO-3-pyridinyl, R2 is Cl and R4 is Cl.
482A Q2 is 5-MeO-3-pyridinyl, R2 is Me and R4 is H.
483A Q2 is 5-MeO-3-pyridinyl, R2 is Cl and R4 is H.
484A Q2 is 5-MeO-3-pyridinyl, R2 is Br and R4 is H.
485A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Cl and R4 is Me.
486A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Cl and R4 is CFH2.
487A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Br and R4 is Me.
488A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is I and R4 is Me.
489A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Me and R4 is Me.
490A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Me and R4 is Cl.
49 IA Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Me and R4 is Br.
492A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Me and R4 is I.
493A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Br and R4 is Br.
494A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Br and R4 is Cl.
495A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Cl and R4 is Br.
496A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Cl and R4 is Cl.
497A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Me and R4 is H.
498A Q2 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Cl and R4 is H.
499A Q2 is 6-Cl- 5-MeO-3-pyridinyl, R2 is Br and R4 is H.
500A Q2 is 6-Cl-3-pyridazinyl, R2 is Cl and R4 is Me.
501A Q2 is 6-Cl-3-pyridazinyl, R2 is Cl and R4 is CFH2.
502A Q2 is 6-Cl-3-pyridazinyl, R2 is Br and R4 is Me.
503A Q2 is 6-Cl-3-pyridazinyl, R2 is I and R4 is Me.
504A Q2 is 6-Cl-3-pyridazinyl, R2 is Me and R4 is Me.
505A Q2 is 6-Cl-3-pyridazinyl, R2 is Me and R4 is Cl.
506A Q2 is 6-Cl-3-pyridazinyl, R2 is Me and R4 is Br.
507A Q2 is 6-Cl-3-pyridazinyl, R2 is Me and R4 is I. Table Row Heading
508A Q2 is 6-Cl-3-pyridazinyl, R2 is Br and R4 is Br. 509A Q2 is 6-Cl-3-pyridazinyl, R2 is Br and R4 is Cl. 510A Q2 is 6-Cl-3-pyridazinyl, R2 is Cl and R4 is Br. 511A Q2 is 6-Cl-3-pyridazinyl, R2 is Cl and R4 is Cl. 512A Q2 is 6-Cl-3-pyridazinyl, R2 is Me and R4 is H. 513A Q2 is 6-Cl-3-pyridazinyl, R2 is Cl and R4 is H. 514A Q2 is 6-Cl-3-pyridazinyl, R2 is Br and R4 is H. 515A Q2 is 6-Me-3-pyridazinyl, R2 is Cl and R4 is Me. 516A Q2 is 6-Me-3-pyridazinyl, R2 is Cl and R4 is CFH2. 517A Q2 is 6-Me-3-pyridazinyl, R2 is Br and R4 is Me. 518A Q2 is 6-Me-3-pyridazinyl, R2 is I and R4 is Me. 519A Q2 is 6-Me-3-pyridazinyl, R2 is Me and R4 is Me. 520A Q2 is 6-Me-3-pyridazinyl, R2 is Me and R4 is Cl. 521A Q2 is 6-Me-3-pyridazinyl, R2 is Me and R4 is Br. 522A Q2 is 6-Me-3-pyridazinyl, R2 is Me and R4 is I. 523A Q2 is 6-Me-3-pyridazinyl, R2 is Br and R4 is Br. 524A Q2 is 6-Me-3-pyridazinyl, R2 is Br and R4 is Cl. 525A Q2 is 6-Me-3-pyridazinyl, R2 is Cl and R4 is Br. 526A Q2 is 6-Me-3-pyridazinyl, R2 is Cl and R4 is Cl. 527A Q2 is 6-Me-3-pyridazinyl, R2 is Me and R4 is H. 528A Q2 is 6-Me-3-pyridazinyl, R2 is Cl and R4 is H. 529A Q2 is 6-Me-3-pyridazinyl, R2 is Br and R4 is H. 530A Q2 is 6-MeO-3-pyridazinyl, R2 is Cl and R4 is Me. 531A Q2 is 6-MeO-3-pyridazinyl, R2 is Cl and R4 is CFH2. 532A Q2 is 6-MeO-3-pyridazinyl, R2 is Br and R4 is Me. 533A Q2 is 6-MeO-3-pyridazinyl, R2 is I and R4 is Me. 534A Q2 is 6-MeO-3-pyridazinyl, R2 is Me and R4 is Me. 535A Q2 is 6-MeO-3-pyridazinyl, R2 is Me and R4 is Cl. 536A Q2 is 6-MeO-3-pyridazinyl, R2 is Me and R4 is Br. 537A Q2 is 6-MeO-3-pyridazinyl, R2 is Me and R4 is I. 538A Q2 is 6-MeO-3-pyridazinyl, R2 is Br and R4 is Br. 539A Q2 is 6-MeO-3-pyridazinyl, R2 is Br and R4 is Cl. 540A Q2 is 6-MeO-3-pyridazinyl, R2 is Cl and R4 is Br. 541A Q2 is 6-MeO-3-pyridazinyl, R2 is Cl and R4 is Cl. 542A Q2 is 6-MeO-3-pyridazinyl, R2 is Me and R4 is H. 543A Q2 is 6-MeO-3-pyridazinyl, R2 is Cl and R4 is H. 544A Q2 is 6-MeO-3-pyridazinyl, R2 is Br and R4 is H. Table Row Heading
545A Q2 is 6-CF3-3-pyridazinyl, R2 is Cl and R4 is Me. 546A Q2 is 6-CF3-3-pyridazinyl, R2 is Cl and R4 is CFH2. 547A Q2 is 6-CF3-3-pyridazinyl, R2 is Br and R4 is Me. 548A Q2 is 6-CF3-3-pyridazinyl, R2 is I and R4 is Me. 549A Q2 is 6-CF3-3-pyridazinyl, R2 is Me and R4 is Me. 550A Q2 is 6-CF3-3-pyridazinyl, R2 is Me and R4 is Cl. 551A Q2 is 6-CF3-3-pyridazinyl, R2 is Me and R4 is Br. 552A Q2 is 6-CF3-3-pyridazinyl, R2 is Me and R4 is I. 553A Q2 is 6-CF3-3-pyridazinyl, R2 is Br and R4 is Br. 554A Q2 is 6-CF3-3-pyridazinyl, R2 is Br and R4 is Cl. 555A Q2 is 6-CF3-3-pyridazinyl, R2 is Cl and R4 is Br. 556A Q2 is 6-CF3-3-pyridazinyl, R2 is Cl and R4 is Cl. 557A Q2 is 6-CF3-3-pyridazinyl, R2 is Me and R4 is H. 558A Q2 is 6-CF3-3-pyridazinyl, R2 is Cl and R4 is H. 559A Q2 is 6-CF3-3-pyridazinyl, R2 is Br and R4 is H. 560A Q2 is 5-Cl-3-pyridazinyl, R2 is Cl and R4 is Me. 561A Q2 is 5-Cl-3-pyridazinyl, R2 is Cl and R4 is CFH2. 562A Q2 is 5-Cl-3-pyridazinyl, R2 is Br and R4 is Me. 563A Q2 is 5-Cl-3-pyridazinyl, R2 is I and R4 is Me. 564A Q2 is 5-Cl-3-pyridazinyl, R2 is Me and R4 is Me. 565A Q2 is 5-Cl-3-pyridazinyl, R2 is Me and R4 is Cl. 566A Q2 is 5-Cl-3-pyridazinyl, R2 is Me and R4 is Br. 567A Q2 is 5-Cl-3-pyridazinyl, R2 is Me and R4 is I. 568A Q2 is 5-Cl-3-pyridazinyl, R2 is Br and R4 is Br. 569A Q2 is 5-Cl-3-pyridazinyl, R2 is Br and R4 is Cl. 570A Q2 is 5-Cl-3-pyridazinyl, R2 is Cl and R4 is Br. 571A Q2 is 5-Cl-3-pyridazinyl, R2 is Cl and R4 is Cl. 572A Q2 is 5-Cl-3-pyridazinyl, R2 is Me and R4 is H. 573A Q2 is 5-Cl-3-pyridazinyl, R2 is Cl and R4 is H. 574A Q2 is 5-Cl-3-pyridazinyl, R2 is Br and R4 is H. 575A Q2 is 5-F-3-pyridazinyl, R2 is Cl and R4 is Me. 576A Q2 is 5-F-3-pyridazinyl, R2 is Cl and R4 is CFH2. 577A Q2 is 5-F-3-pyridazinyl, R2 is Br and R4 is Me. 578A Q2 is 5-F-3-pyridazinyl, R2 is I and R4 is Me. 579A Q2 is 5-F-3-pyridazinyl, R2 is Me and R4 is Me. 580A Q2 is 5-F-3-pyridazinyl, R2 is Me and R4 is Cl. 581A Q2 is 5-F-3-pyridazinyl, R2 is Me and R4 is Br. Table Row Heading
582 A Q2 is 5-F-3-pyridazinyl, R2 is Me and R4 is I.
583A Q2 is 5-F-3-pyridazinyl, R2 is Br and R4 is Br.
584A Q2 is 5-F-3-pyridazinyl, R2 is Br and R4 is Cl.
585A Q2 is 5-F-3-pyridazinyl, R2 is Cl and R4 is Br.
586A Q2 is 5-F-3-pyridazinyl, R2 is Cl and R4 is Cl.
587A Q2 is 5-F-3-pyridazinyl, R2 is Me and R4 is H.
588A Q2 is 5-F-3-pyridazinyl, R2 is Cl and R4 is H.
589 A Q2 is 5-F-3-pyridazinyl, R2 is Br and R4 is H.
590A Q2 is 5-MeO-3-pyridazinyl, R2 is Cl and R4 is Me.
591A Q2 is 5-MeO-3-pyridazinyl, R2 is Cl and R4 is CFH2.
592A Q2 is 5-MeO-3-pyridazinyl, R2 is Br and R4 is Me.
593A Q2 is 5-MeO-3-pyridazinyl, R2 is I and R4 is Me.
594A Q2 is 5-MeO-3-pyridazinyl, R2 is Me and R4 is Me.
595A Q2 is 5-MeO-3-pyridazinyl, R2 is Me and R4 is Cl.
596A Q2 is 5-MeO-3-pyridazinyl, R2 is Me and R4 is Br.
597A Q2 is 5-MeO-3-pyridazinyl, R2 is Me and R4 is I.
598A Q2 is 5-MeO-3-pyridazinyl, R2 is Br and R4 is Br.
599A Q2 is 5-MeO-3-pyridazinyl, R2 is Br and R4 is Cl.
600A Q2 is 5-MeO-3-pyridazinyl, R2 is Cl and R4 is Br.
601A Q2 is 5-MeO-3-pyridazinyl, R2 is Cl and R4 is Cl.
602A Q2 is 5-MeO-3-pyridazinyl, R2 is Me and R4 is H.
603A Q2 is 5-MeO-3-pyridazinyl, R2 is Cl and R4 is H.
604A Q2 is 5-MeO-3-pyridazinyl, R2 is Br and R4 is H.
605A Q2 is 2-Cl-5-pyrimidinyl, R2 is Cl and R4 is Me.
606A Q2 is 2-Cl-5-pyrimidinyl, R2 is Cl and R4 is CFH2.
607A Q2 is 2-Cl-5-pyrimidinyl, R2 is Br and R4 is Me.
608A Q2 is 2-Cl-5-pyrimidinyl, R2 is I and R4 is Me.
609A Q2 is 2-Cl-5-pyrimidinyl, R2 is Me and R4 is Me.
610A Q2 is 2-C1-5 pyrimidinyl, R2 is Me and R4 is Cl.
611A Q2 is 2-Cl-5-pyrimidinyl, R2 is Me and R4 is Br.
612A Q2 is 2-C1-5 -pyrimidinyl, R2 is Me and R4 is I.
613A Q2 is 2-Cl-5-pyrimidinyl, R2 is Br and R4 is Br.
614A Q2 is 2-C1-5 -pyrimidinyl, R2 is Br and R4 is Cl.
615A Q2 is 2-Cl-5-pyrimidinyl, R2 is Cl and R4 is Br.
616A Q2 is 2-C1-5 -pyrimidinyl, R2 is Cl and R4 is Cl.
617A Q2 is 2-C1-5 -pyrimidinyl, R2 is Me and R4 is H.
618A Q2 is 2-Cl-5-pyrimidinyl, R2 is Cl and R4 is H. Table Row Heading
619A Q2 is 2-Cl-5-pyrimidinyl, R2 is '. 3r and R4 is H.
620A Q2 is 2-Me-5-pyrimidinyl, R2 is Cl and R4 is Me.
62 IA Q2 is 2-Me-5-pyrimidinyl, R2 is Cl and R4 is CFH2.
622A Q2 is 2-Me-5-pyrimidinyl, R2 is Br and R4 is Me.
623A Q2 is 2-Me-5-pyrimidinyl, R2 is I and R4 is Me.
624A Q2 is 2-Me-5-pyrimidinyl, R2 is Me and R4 is Me.
625A Q2 is 2-Me-5-pyrimidinyl, R2 is Me and R4 is Cl.
626A Q2 is 2-Me-5-pyrimidinyl, R2 is Me and R4 is Br.
627A Q2 is 2-Me-5-pyrimidinyl, R2 is Me and R4 is I.
628A Q2 is 2-Me-5-pyrimidinyl, R2 is Br and R4 is Br.
629A Q2 is 2-Me-5-pyrimidinyl, R2 is Br and R4 is Cl.
630A Q2 is 2-Me-5-pyrimidinyl, R2 is Cl and R4 is Br.
63 IA Q2 is 2-Me-5-pyrimidinyl, R2 is Cl and R4 is Cl.
632A Q2 is 2-Me-5-pyrimidinyl, R2 is Me and R4 is H.
633A Q2 is 2-Me-5-pyrimidinyl, R2 is Cl and R4 is H.
634A Q2 is 2-Me-5-pyrimidinyl, R2 is Br and R4 is H.
635 A Q2 is 2-MeO-5-pyrimidinyl, R2 is Cl and R4 is Me.
636A Q2 is 2-MeO-5-pyrimidinyl, R2 is Cl and R4 is CFH2.
637 A Q2 is 2-MeO-5-pyrimidinyl, R2 is Br and R4 is Me.
638A Q2 is 2-MeO-5-pyrimidinyl, R2 is I and R4 is Me.
639A Q2 is 2-MeO-5-pyrimidinyl, R2 is Me and R4 is Me.
640A Q2 is 2-MeO-5-pyrimidinyl, R2 is Me and R4 is Cl.
641A Q2 is 2-MeO-5-pyrimidinyl, R2 is Me and R4 is Br.
642A Q2 is 2-MeO-5-pyrimidinyl, R2 is Me and R4 is I.
643A Q2 is 2-MeO-5 pyrimidinyl, R2 is Br and R4 is Br.
644A Q2 is 2-MeO-5-pyrimidinyl, R2 is Br and R4 is Cl.
645A Q2 is 2-MeO-5-pyrimidinyl, R2 is Cl and R4 is Br.
646A Q2 is 2-MeO-5-pyrimidinyl, R2 is Cl and R4 is Cl.
647A Q2 is 2-MeO-5-pyrimidinyl, R2 is Me and R4 is H.
648A Q2 is 2-MeO-5-pyrimidinyl, R2 is Cl and R4 is H.
649A Q2 is 2-MeO-5-pyrimidinyl, R2 is Br and R4 is H.
650A Q2 is 2-CF3-5-pyrimidinyl, R2 is Cl and R4 is Me.
65 IA Q2 is 2-CF3-5-pyrimidinyl, R2 i s Cl and R4 is CFH2.
652A Q2 is 2-CF3-5-pyrimidinyl, R2 is Br and R4 is Me.
653A Q2 is 2-CF3-5-pyrimidinyl, R2 i s I and R4 is Me.
654A Q2 is 2-CF3-5-pyrimidinyl, R2 i s Me and R4 is Me.
655A Q2 is 2-CF3-5-pyrimidinyl, R2 i s Me and R4 is Cl. Table Row Heading
656A Q2 is 2-CF3-5-pyrimidinyl, R2 is Me and R4 is Br.
657A Q2 is 2-CF3-5-pyrimidinyl, R2 is Me and R4 is I.
658 A Q2 is 2-CF3-5-pyrimidinyl, R2 is Br and R4 is Br.
659A Q2 is 2-CF3-5-pyrimidinyl, R2 is Br and R4 is Cl.
660A Q2 is 2-CF3-5-pyrimidinyl, R2 is Cl and R4 is Br.
661A Q2 is 2-CF3-5-pyrimidinyl, R2 is Cl and R4 is Cl.
662A Q2 is 2-CF3-5-pyrimidinyl, R2 is Me and R4 is H.
663A Q2 is 2-CF3-5-pyrimidinyl, R2 is Cl and R4 is H.
664A Q2 is 2-CF3-5-pyrimidinyl, R2 is Br and R4 is H.
665A Q2 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is Me.
666A Q2 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is CFH2.
667A Q2 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is Me.
668A Q2 is 5-Cl-2-pyrimidinyl, R2 is I and R4 is Me.
669A Q2 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is Me.
670A Q2 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is Cl.
671A Q2 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is Br.
672A Q2 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is I.
673A Q2 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is Br.
674A Q2 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is Cl.
675A Q2 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is Br.
676A Q2 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is Cl.
677A Q2 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is H.
678A Q2 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is H.
679A Q2 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is H.
680A Q2 is 5-Me-2-pyrimidinyl, R2 is Cl and R4 is Me.
681A Q2 is 5-Me-2-pyrimidinyl, R2 is Cl and R4 is CFH2.
682A Q2 is 5-Me-2-pyrimidinyl, R2 is Br and R4 is Me.
683A Q2 is 5-Me-2-pyrimidinyl, R2 is I and R4 is Me.
684A Q2 is 5-Me-2-pyrimidinyl, R2 is Me and R4 is Me.
685A Q2 is 5-Me-2-pyrimidinyl, R2 is Me and R4 is Cl.
686A Q2 is 5-Me-2-pyrimidinyl, R2 is Me and R4 is Br.
687A Q2 is 5-Me-2-pyrimidinyl, R2 is Me and R4 is I.
688A Q2 is 5-Me-2-pyrimidinyl, R2 is Br and R4 is Br.
689A Q2 is 5-Me-2-pyrimidinyl, R2 is Br and R4 is Cl.
690A Q2 is 5-Me-2-pyrimidinyl, R2 is Cl and R4 is Br.
69 IA Q2 is 5-Me-2-pyrimidinyl, R2 is Cl and R4 is Cl.
692A Q2 is 5-Me-2-pyrimidinyl, R2 is Me and R4 is H. Table Row Heading
693A Q2 is 5-Me-2-pyrimidinyl, R2 is Cl and R4 is H.
694A Q2 is 5-Me-2-pyrimidinyl, R2 is Br and R4 is H.
695A Q2 is 5-MeO-2-pyrimidinyl, R2 is Cl and R4 is Me.
696A Q2 is 5-MeO-2-pyrimidinyl, R2 is Cl and R4 is CFH2.
697A Q2 is 5-MeO-2-pyrimidinyl, R2 is Br and R4 is Me.
698A Q2 is 5-MeO-2-pyrimidinyl, R2 is I and R4 is Me.
699A Q2 is 5-MeO-2-pyrimidinyl, R2 is Me and R4 is Me.
700A Q2 is 5-MeO-2-pyrimidinyl, R2 is Me and R4 is Cl.
701A Q2 is 5-MeO-2-pyrimidinyl, R2 is Me and R4 is Br.
702A Q2 is 5-MeO-2-pyrimidinyl, R2 is Me and R4 is I.
703A Q2 is 5-MeO-2-pyrimidinyl, R2 is Br and R4 is Br.
704A Q2 is 5-MeO-2-pyrimidinyl, R2 is Br and R4 is Cl.
705A Q2 is 5-MeO-2-pyrimidinyl, R2 is Cl and R4 is Br.
706A Q2 is 5-MeO-2-pyrimidinyl, R2 is Cl and R4 is Cl.
707A Q2 is 5-MeO-2-pyrimidinyl, R2 is Me and R4 is H.
708A Q2 is 5-MeO-2-pyrimidinyl, R2 is Cl and R4 is H.
709A Q2 is 5-MeO-2-pyrimidinyl, R2 is Br and R4 is H.
710A Q2 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is Me.
711A Q2 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is CFH2.
712A Q2 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is Me.
713A Q2 is 5-Cl-2-pyrimidinyl, R2 is I and R4 is Me.
714A Q2 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is Me.
715A Q2 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is Cl.
716A Q2 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is Br.
717A Q2 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is I.
718A Q2 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is Br.
719A Q2 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is Cl.
720A Q2 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is Br.
721A Q2 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is Cl.
722A Q2 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is H.
723A Q2 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is H.
724A Q2 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is H.
725A Q2 is 5-CF3-2-pyrimidinyl, R2 is Cl and R4 is Me.
726A Q2 is 5-CF3-2-pyrimidinyl, R2 is Cl and R4 is CFH2.
727A Q2 is 5-CF3-2-pyrimidinyl, R2 is Br and R4 is Me.
728A Q2 is 5-CF3-2-pyrimidinyl, R2 is I and R4 is Me.
729A Q2 is 5-CF3-2-pyrimidinyl, R2 is Me and R4 is Me. Table Row Heading
730A Q2 is 5-CF3-2-pyrimidinyl, R2 is Me and R4 is Cl.
73 IA Q2 is 5-CF3-2-pyrimidinyl, R2 is Me and R4 is Br.
732A Q2 is 5-CF3-2-pyrimidinyl, R2 is Me and R4 is I.
733A Q2 is 5-CF3-2-pyrimidinyl, R2 is Br and R4 is Br.
734A Q2 is 5-CF3-2-pyrimidinyl, R2 is Br and R4 is Cl.
735A Q2 is 5-CF3-2-pyrimidinyl, R2 is Cl and R4 is Br.
736A Q2 is 5-CF3-2-pyrimidinyl, R2 is Cl and R4 is Cl.
737A Q2 is 5-CF3-2-pyrimidinyl, R2 is Me and R4 is H.
738A Q2 is 5-CF3-2-pyrimidinyl, R2 is Cl and R4 is H.
739A Q2 is 5-CF3-2-pyrimidinyl, R2 is Br and R4 is H.
740A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Cl and R4 is Me.
741A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Cl and R4 is CFH2.
742A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Br and R4 is Me.
743A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is I and R4 is Me.
744A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Me and R4 is Me.
745A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Me and R4 is Cl.
746A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Me and R4 is Br.
747A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Me and R4 is I.
748A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Br and R4 is Br.
749A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Br and R4 is Cl.
750A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Cl and R4 is Br.
751A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Cl and R4 is Cl.
752A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Me and R4 is H.
753A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Cl and R4 is H.
754A Q2 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Br and R4 is H.
755A Q2 is 5-Me-2-thienyl, R2 is Cl and R4 is Me.
756A Q2 is 5-Me-2-thienyl, R2 is Cl and R4 is CFH2.
757A Q2 is 5-Me-2-thienyl, R2 is Br and R4 is Me.
758A Q2 is 5-Me-2-thienyl, R2 is I and R4 is Me.
759A Q2 is 5-Me-2-thienyl, R2 is Me and R4 is Me.
760A Q2 is 5-Me-2-thienyl, R2 is Me and R4 is Cl.
761A Q2 is 5-Me-2-thienyl, R2 is Me and R4 is Br.
762A Q2 is 5-Me-2-thienyl, R2 is Me and R4 is I.
763A Q2 is 5-Me-2-thienyl, R2 is Br and R4 is Br.
764A Q2 is 5-Me-2-thienyl, R2 is Br and R4 is Cl.
765A Q2 is 5-Me-2-thienyl, R2 is Cl and R4 is Br.
766A Q2 is 5-Me-2-thienyl, R2 is Cl and R4 is Cl. Table Row Heading
767A Q2 is 5-Me-2-thienyl, R2 is Me and R4 is H.
768A Q2 is 5-Me-2-thienyl, R2 is Cl and R4 is H.
769A Q2 is 5-Me-2-thienyl, R2 is Br and R4 is H.
770A Q2 is 5-Cl-2-thienyl, R2 is Cl and R4 is Me.
771A Q2 is 5-Cl-2-thienyl, R2 is Cl and R4 is CFH2.
772A Q2 is 5-Cl-2-thienyl, R2 is Br and R4 is Me.
773A Q2 is 5-Cl-2-thienyl, R2 is I and R4 is Me.
774A Q2 is 5-Cl-2-thienyl, R2 is Me and R4 is Me.
775A Q2 is 5-Cl-2-thienyl, R2 is Me and R4 is Cl.
776A Q2 is 5-Cl-2-thienyl, R2 is Me and R4 is Br.
777A Q2 is 5-Cl-2-thienyl, R2 is Me and R4 is I.
778A Q2 is 5-Cl-2-thienyl, R2 is Br and R4 is Br.
779A Q2 is 5-Cl-2-thienyl, R2 is Br and R4 is Cl.
780A Q2 is 5-Cl-2-thienyl, R2 is Cl and R4 is Br.
781A Q2 is 5-Cl-2-thienyl, R2 is Cl and R4 is Cl.
782A Q2 is 5-Cl-2-thienyl, R2 is Me and R4 is H.
783A Q2 is 5-Cl-2-thienyl, R2 is Cl and R4 is H.
784A Q2 is 5-Cl-2-thienyl, R2 is Br and R4 is H.
785A Q2 is 5-F-2-thienyl, R2 is Cl and R4 is Me.
786A Q2 is 5-F-2-thienyl, R2 is Cl and R4 is CFH2.
787A Q2 is 5-F-2-thienyl, R2 is Br and R4 is Me.
788A Q2 is 5-F-2-thienyl, R2 is I and R4 is Me.
789A Q2 is 5-F-2-thienyl, R2 is Me and R4 is Me.
790A Q2 is 5-F-2-thienyl, R2 is Me and R4 is Cl.
791A Q2 is 5-F-2-thienyl, R2 is Me and R4 is Br.
792A Q2 is 5-F-2-thienyl, R2 is Me and R4 is I.
793A Q2 is 5-F-2-thienyl, R2 is Br and R4 is Br.
794A Q2 is 5-F-2-thienyl, R2 is Br and R4 is Cl.
795A Q2 is 5-F-2-thienyl, R2 is Cl and R4 is Br.
796A Q2 is 5-F-2-thienyl, R2 is Cl and R4 is Cl.
797A Q2 is 5-F-2-thienyl, R2 is Me and R4 is H.
798A Q2 is 5-F-2-thienyl, R2 is Cl and R4 is H.
799A Q2 is 5-F-2-thienyl, R2 is Br and R4 is H.
800A Q2 is 5-Me-3-thienyl, R2 is Cl and R4 is Me.
801A Q2 is 5-Me-3-thienyl, R2 is Cl and R4 is CFH2.
802A Q2 is 5-Me-3-thienyl, R2 is Br and R4 is Me.
803A Q2 is 5-Me-3-thienyl, R2 is I and R4 is Me. Table Row Heading
804A Q2 is 5-Me-3-thienyl, R2 is Me and R4 is Me.
805A Q2 is 5-Me-3-thienyl, R2 is Me and R4 is Cl.
806A Q2 is 5-Me-3-thienyl, R2 is Me and R4 is Br.
807A Q2 is 5-Me-3-thienyl, R2 is Me and R4 is I.
808A Q2 is 5-Me-3-thienyl, R2 is Br and R4 is Br.
809A Q2 is 5-Me-3-thienyl, R2 is Br and R4 is Cl.
810A Q2 is 5-Me-3-thienyl, R2 is Cl and R4 is Br.
811A Q2 is 5-Me-3-thienyl, R2 is Cl and R4 is Cl.
812A Q2 is 5-Me-3-thienyl, R2 is Me and R4 is H.
813A Q2 is 5-Me-3-thienyl, R2 is Cl and R4 is H.
814A Q2 is 5-Me-3-thienyl, R2 is Br and R4 is H.
815A Q2 is 5-Cl-3-thienyl, R2 is Cl and R4 is Me.
816A Q2 is 5-Cl-3-thienyl, R2 is Cl and R4 is CFH2.
817A Q2 is 5-Cl-3-thienyl, R2 is Br and R4 is Me.
818A Q2 is 5-Cl-3-thienyl, R2 is I and R4 is Me.
819A Q2 is 5-Cl-3-thienyl, R2 is Me and R4 is Me.
820A Q2 is 5-Cl-3-thienyl, R2 is Me and R4 is Cl.
821A Q2 is 5-Cl-3-thienyl, R2 is Me and R4 is Br.
822A Q2 is 5-Cl-3-thienyl, R2 is Me and R4 is I.
823A Q2 is 5-Cl-3-thienyl, R2 is Br and R4 is Br.
824A Q2 is 5-Cl-3-thienyl, R2 is Br and R4 is Cl.
825A Q2 is 5-Cl-3-thienyl, R2 is Cl and R4 is Br.
826A Q2 is 5-Cl-3-thienyl, R2 is Cl and R4 is Cl.
827A Q2 is 5-Cl-3-thienyl, R2 is Me and R4 is H.
828A Q2 is 5-Cl-3-thienyl, R2 is Cl and R4 is H.
829A Q2 is 5-Cl-3-thienyl, R2 is Br and R4 is H.
830A Q2 is 5-F-3-thienyl, R2 is Cl and R4 is Me.
83 IA Q2 is 5-F-3-thienyl, R2 is Cl and R4 is CFH2.
832A Q2 is 5-F-3-thienyl, R2 is Br and R4 is Me.
833A Q2 is 5-F-3-thienyl, R2 is I and R4 is Me.
834A Q2 is 5-F-3-thienyl, R2 is Me and R4 is Me.
835A Q2 is 5-F-3-thienyl, R2 is Me and R4 is Cl.
836A Q2 is 5-F-3-thienyl, R2 is Me and R4 is Br.
837A Q2 is 5-F-3-thienyl, R2 is Me and R4 is I.
838A Q2 is 5-F-3-thienyl, R2 is Br and R4 is Br.
839A Q2 is 5-F-3-thienyl, R2 is Br and R4 is Cl.
840A Q2 is 5-F-3-thienyl, R2 is Cl and R4 is Br. Table Row Heading
841A Q2 is 5-F-3-thienyl, R2 is Cl and R4 is Cl.
842A Q2 is 5-F-3-thienyl, R2 is Me and R4 is H.
843A Q2 is 5-F-3-thienyl, R2 is Cl and R4 is H.
844A Q2 is 5-F-3-thienyl, R2 is Br and R4 is H.
845A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Cl and R4 is Me.
846A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Cl and R4 is CFH2.
847A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Br and R4 is Me.
848A Q2 is l-Me-l//-pyrazol-3-yl, R2 is I and R4 is Me.
849A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Me and R4 is Me.
850A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Me and R4 is Cl.
851A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Me and R4 is Br.
852A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Me and R4 is I.
853A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Br and R4 is Br.
854A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Br and R4 is Cl.
855A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Cl and R4 is Br.
856A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Cl and R4 is Cl.
857A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Me and R4 is H.
858A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Cl and R4 is H.
859A Q2 is l-Me-l//-pyrazol-3-yl, R2 is Br and R4 is H.
860A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Cl and R4 is Me.
861A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Cl and R4 is CFH2.
862A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Br and R4 is Me.
863A Q2 is l-Me-l//-pyrazol-4-yl, R2 is I and R4 is Me.
864A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Me and R4 is Me.
865A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Me and R4 is Cl.
866A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Me and R4 is Br.
867A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Me and R4 is I.
868A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Br and R4 is Br.
869A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Br and R4 is Cl.
870A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Cl and R4 is Br.
871A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Cl and R4 is Cl.
872A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Me and R4 is H.
873A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Cl and R4 is H.
874A Q2 is l-Me-l//-pyrazol-4-yl, R2 is Br and R4 is H.
875A Q2 is 2-Me-5-thiazolyl, R2 is Cl and R4 is Me.
876A Q2 is 2-Me-5-thiazolyl, R2 is Cl and R4 is CFH2.
877A Q2 is 2-Me-5-thiazolyl, R2 is Br and R4 is Me. Table Row Heading
878A Q2 is 2-Me-5-thiazolyl, R2 is I and R4 is Me.
879A Q2 is 2-Me-5-thiazolyl, R2 is Me and R4 is Me.
880A Q2 is 2-Me-5-thiazolyl, R2 is Me and R4 is Cl.
881A Q2 is 2-Me-5-thiazolyl, R2 is Me and R4 is Br.
882A Q2 is 2-Me-5-thiazolyl, R2 is Me and R4 is I.
883A Q2 is 2-Me-5-thiazolyl, R2 is Br and R4 is Br.
884A Q2 is 2-Me-5-thiazolyl, R2 is Br and R4 is Cl.
885A Q2 is 2-Me-5-thiazolyl, R2 is Cl and R4 is Br.
886A Q2 is 2-Me-5-thiazolyl, R2 is Cl and R4 is Cl.
887A Q2 is 2-Me-5-thiazolyl, R2 is Me and R4 is H.
888A Q2 is 2-Me-5-thiazolyl, R2 is Cl and R4 is H.
889A Q2 is 2-Me-5-thiazolyl, R2 is Br and R4 is H.
890A Q2 is 2-Cl-5-thiazolyl, R2 is Cl and R4 is Me.
891A Q2 is 2-Cl-5-thiazolyl, R2 is Cl and R4 is CFH2.
892A Q2 is 2-Cl-5-thiazolyl, R2 is Br and R4 is Me.
893A Q2 is 2-Cl-5-thiazolyl, R2 is I and R4 is Me.
894A Q2 is 2-Cl-5-thiazolyl, R2 is Me and R4 is Me.
895A Q2 is 2-Cl-5-thiazolyl, R2 is Me and R4 is Cl.
896A Q2 is 2-Cl-5-thiazolyl, R2 is Me and R4 is Br.
897A Q2 is 2-Cl-5-thiazolyl, R2 is Me and R4 is I.
898A Q2 is 2-Cl-5-thiazolyl, R2 is Br and R4 is Br.
899A Q2 is 2-Cl-5-thiazolyl, R2 is Br and R4 is Cl.
900A Q2 is 2-Cl-5-thiazolyl, R2 is Cl and R4 is Br.
901A Q2 is 2-Cl-5-thiazolyl, R2 is Cl and R4 is Cl.
902A Q2 is 2-Cl-5-thiazolyl, R2 is Me and R4 is H.
903A Q2 is 2-Cl-5-thiazolyl, R2 is Cl and R4 is H.
904A Q2 is 2-Cl-5-thiazolyl, R2 is Br and R4 is H.
905A Q2 is 5-Me-3-isothiazolyl, R2 is Cl and R4 is Me.
906A Q2 is 5-Me-3-isothiazolyl, R2 is Cl and R4 is CFH2.
907A Q2 is 5-Me-3-isothiazolyl, R2 is Br and R4 is Me.
908A Q2 is 5-Me-3-isothiazolyl, R2 is I and R4 is Me.
909A Q2 is 5-Me-3-isothiazolyl, R2 is Me and R4 is Me.
910A Q2 is 5-Me-3-isothiazolyl, R2 is Me and R4 is Cl.
911A Q2 is 5-Me-3-isothiazolyl, R2 is Me and R4 is Br.
912A Q2 is 5-Me-3-isothiazolyl, R2 is Me and R4 is I.
913A Q2 is 5-Me-3-isothiazolyl, R2 is Br and R4 is Br.
914A Q2 is 5-Me-3-isothiazolyl, R2 is Br and R4 is Cl. Table Row Heading
915A Q2 is 5-Me-3-isothiazolyl, R' 1 is Cl and R4 is Br.
916A Q2 is 5-Me-3-isothiazolyl, R2 is Cl and R4 is Cl.
917A Q2 is 5-Me-3-isothiazolyl, R" 1 is Me and R4 is H.
918A Q2 is 5-Me-3-isothiazolyl, R2 is Cl and R4 is H.
919A Q2 is 5-Me-3-isothiazolyl, R" 1 is Br and R4 is H.
920A Q2 is 5-Cl-3-isothiazolyl, R2 is Cl and R4 is Me.
921A Q2 is 5-Cl-3-isothiazolyl, R2 is Cl and R4 is CFH2.
922A Q2 is 5-Cl-3-isothiazolyl, R2 is Br and R4 is Me.
923A Q2 is 5-Cl-3-isothiazolyl, R2 is I and R4 is Me.
924A Q2 is 5-Cl-3-isothiazolyl, R2 is Me and R4 is Me.
925A Q2 is 5-Cl-3-isothiazolyl, R2 is Me and R4 is Cl.
926A Q2 is 5-Cl-3-isothiazolyl, R2 is Me and R4 is Br.
927A Q2 is 5-Cl-3-isothiazolyl, R2 is Me and R4 is I.
928A Q2 is 5-Cl-3-isothiazolyl, R2 is Br and R4 is Br.
929A Q2 is 5-Cl-3-isothiazolyl, R2 is Br and R4 is Cl.
930A Q2 is 5-Cl-3-isothiazolyl, R2 is Cl and R4 is Br.
93 IA Q2 is 5-Cl-3-isothiazolyl, R2 is Cl and R4 is Cl.
932A Q2 is 5-Cl-3-isothiazolyl, R2 is Me and R4 is H.
933A Q2 is 5-Cl-3-isothiazolyl, R2 is Cl and R4 is H.
934A Q2 is 5-Cl-3-isothiazolyl, R2 is Br and R4 is H.
Table 2
Figure imgf000113_0001
Ql is zμCl-Ph, R2 is Cl and R4 is Me.
(R5b)n (R5b)n (R5b)n
2,6-di-F 2,4-di-Cl 4-CN, 2,6-di-F
2,4,6-tri-F 2-Cl, 4, 6-di-F 2,6-di-F, 4-Me
2,3,6-tri-F 2-Cl, 6-F 2-Cl, 5-CF3
2,4,5-tri-F 2-Br, 6-F 2-Cl, 4-Me
2,3,4-tri-F 2-F, 6-CF3 2-Cl, 4-MeO
Figure imgf000113_0002
Q1 is 4-Cl-Ph, R2 is Cl and R4 is Me.
(R5b)n
2-Br, 4-MeO
2,6-di-F, 3 -Cl
2,6-di-F, 3 -CN
2,6-di-F, 3-MeO
2,6-di-F, 4-CF2HO
2,6-di-F, 3-CF2HO
Figure imgf000114_0001
Figure imgf000114_0002
The present disclosure also includes Tables IB through 934B, each of which is constructed the same as Table 2 above except that the row heading in Table 2 (i.e. "Q1 is 4-Cl-Ph, R2 is Cl and R4 is Me") is replaced with the respective row heading shown below. Thus, for example, in Table IB the row heading is "Q1 is 4-Cl-Ph, R2 is Cl and R4 is CFH2", and (R5^)n is as defined in Table 2 above. Tables 2B through 934B are constructed similarly.
Table Row Heading
IB Q1 is 4-Cl-Ph, R2 is Cl and R4 is CFH2.
2B Q1 is 4-Cl-Ph, R2 is Br and R4 is Me.
3B Q1 is 4-Cl-Ph, R2 is I and R4 is Me.
4B Q1 is 4-Cl-Ph, R2 is Me and R4 is Me.
5B Q1 is 4-Cl-Ph, R2 is Me and R4 is Cl.
6B Q1 is 4-Cl-Ph, R2 is Me and R4 is Br.
7B Q1 is 4-Cl-Ph, R2 is Me and R4 is I.
8B Q1 is 4-Cl-Ph, R2 is Me and R4 is MeO.
9B Q1 is 4-Cl-Ph, R2 is MeO and R4 is Me.
1OB Q1 is 4-Cl-Ph, R2 is Br and R4 is Br.
HB Q1 is 4-Cl-Ph, R2 is Br and R4 is Cl.
12B Q1 is 4-Cl-Ph, R2 is Cl and R4 is Br.
13B Q1 is 4-Cl-Ph, R2 is Cl and R4 is Cl.
14B Q1 is 4-Cl-Ph, R2 is Me and R4 is MeS.
15B Q1 is 4-Cl-Ph, R2 is MeS and R4 is Me.
16B Q1 is 4-Cl-Ph, R2 is Et and R4 is Br.
17B Q1 is 4-Cl-Ph, R2 is Et and R4 is Cl.
18B Q1 is 4-Cl-Ph, R2 is Et and R4 is Me.
19B Q1 is 4-Cl-Ph, R2 is Me and R4 is Et.
2OB Q1 is 4-Cl-Ph, R2 is Cl and R4 is Et.
21B Q1 is 4-Cl-Ph, R2 is Me and R4 is CN.
22B Q1 is 4-Cl-Ph, R2 is Me and R4 is H. Table Row Heading
23B Q1 is 4-Cl-Ph, R2 is Cl and R4 is H.
24B Q1 is 4-Cl-Ph, R2 is Br and R4 is H.
25B Q1 is 3 -Cl-Ph, R2 is Cl and R4 is Me.
26B Q1 is 3 -Cl-Ph, R2 is Cl and R4 is CFH2.
27B Q1 is 3 -Cl-Ph, R2 is Br and R4 is Me.
28B Q1 is 3 -Cl-Ph, R2 is I and R4 is Me.
29B Q1 is 3 -Cl-Ph, R2 is Me and R4 is Me.
3OB Q1 is 3 -Cl-Ph, R2 is Me and R4 is Cl.
31B Q1 is 3 -Cl-Ph, R2 is Me and R4 is Br.
32B Q1 is 3 -Cl-Ph, R2 is Me and R4 is I.
33B Q1 is 3 -Cl-Ph, R2 is Br and R4 is Br.
34B Q1 is 3 -Cl-Ph, R2 is Br and R4 is Cl.
35B Q1 is 3 -Cl-Ph, R2 is Cl and R4 is Br.
36B Q1 is 3 -Cl-Ph, R2 is Cl and R4 is Cl.
37B Q1 is 3 -Cl-Ph, R2 is Me and R4 is H.
38B Q1 is 3 -Cl-Ph, R2 is Cl and R4 is H.
39B Q1 is 3 -Cl-Ph, R2 is Br and R4 is H
4OB Q1 is 4-F-Ph, R2 is Cl and R4 is Me.
41B Q1 is 4-F-Ph, R2 is Cl and R4 is CFH2.
42B Q1 is 4-F-Ph, R2 is Br and R4 is Me.
43B Q1 is 4-F-Ph, R2 is I and R4 is Me.
44B Q1 is 4-F-Ph, R2 is Me and R4 is Me.
45B Q1 is 4-F-Ph, R2 is Me and R4 is Cl.
46B Q1 is 4-F-Ph, R2 is Me and R4 is Br.
47B Q1 is 4-F-Ph, R2 is Me and R4 is I.
48B Q1 is 4-F-Ph, R2 is Br and R4 is Br.
49B Q1 is 4-F-Ph, R2 is Br and R4 is Cl.
5OB Q1 is 4-F-Ph, R2 is Cl and R4 is Br.
51B Q1 is 4-F-Ph, R2 is Cl and R4 is Cl.
52B Q1 is 4-F-Ph, R2 is Me and R4 is H.
53B Q1 is 4-F-Ph, R2 is Cl and R4 is H.
54B Q1 is 4-F-Ph, R2 is Br and R4 is H.
55B Q1 is 3-F-Ph, R2 is Cl and R4 is Me.
56B Q1 is 3-F-Ph, R2 is Cl and R4 is CFH2.
57B Q1 is 3-F-Ph, R2 is Br and R4 is Me.
58B Q1 is 3-F-Ph, R2 is I and R4 is Me.
59B Q1 is 3-F-Ph, R2 is Me and R4 is Me. Table Row Heading
6OB Q1 is 3-F-Ph, R2 is Me and R4 is Cl.
61B Q1 is 3-F-Ph, R2 is Me and R4 is Br.
62B Q1 is 3-F-Ph, R2 is Me and R4 is I.
63B Q1 is 3-F-Ph, R2 is Br and R4 is Br.
64B Q1 is 3-F-Ph, R2 is Br and R4 is Cl.
65B Q1 is 3-F-Ph, R2 is Cl and R4 is Br.
66B Q1 is 3-F-Ph, R2 is Cl and R4 is Cl.
67B Q1 is 3-F-Ph, R2 is Me and R4 is H.
68B Q1 is 3-F-Ph, R2 is Cl and R4 is H.
69B Q1 is 3-F-Ph, R2 is Br and R4 is H
7OB Q1 is 3-CF2HO-Ph , R2 is Cl and R4 is Me.
71B Q1 is 3-CF2HO-Ph , R2 is Cl and R4 is CH2F
72B Q1 is 3-CF2HO-Ph , R2 is Br and R4 is Me.
73B Q1 is 3-CF2HO-Ph , R2 is I and R4 is Me.
74B Q1 is 3-CF2HO-Ph , R2 is Me and R4 is Me.
75B Q1 is 3-CF2HO-Ph , R2 is Me and R4 is Cl.
76B Q1 is 3-CF2HO-Ph , R2 is Me and R4 is Br.
77B Q1 is 3-CF2HO-Ph , R2 is Me and R4 is I.
78B Q1 is 3-CF2HO-Ph , R2 is Br and R4 is Br.
79B Q1 is 3-CF2HO-Ph , R2 is Br and R4 is Cl.
8OB Q1 is 3-CF2HO-Ph , R2 is Cl and R4 is Br.
81B Q1 is 3-CF2HO-Ph , R2 is Cl and R4 is Cl.
82B Q1 is 3-CF2HO-Ph , R2 is Me and R4 is H.
83B Q1 is 3-CF2HO-Ph , R2 is Cl and R4 is H.
84B Q1 is 3-CF2HO-Ph , R2 is Br and R4 is H
85B Q1 is 4-Me-Ph, R2 is Cl and R4 is Me.
86B Q1 is 4-Me-Ph, R2 is Cl and R4 is CFH2.
87B Q1 is 4-Me-Ph, R2 is Br and R4 is Me.
88B Q1 is 4-Me-Ph, R2 is I and R4 is Me.
89B Q1 is 4-Me-Ph, R2 is Me and R4 is Me.
9OB Q1 is 4-Me-Ph, R2 is Me and R4 is Cl.
91B Q1 is 4-Me-Ph, R2 is Me and R4 is Br.
92B Q1 is 4-Me-Ph, R2 is Me and R4 is I.
93B Q1 is 4-Me-Ph, R2 is Br and R4 is Br.
94B Q1 is 4-Me-Ph, R2 is Br and R4 is Cl.
95B Q1 is 4-Me-Ph, R2 is Cl and R4 is Br.
96B Q1 is 4-Me-Ph, R2 is Cl and R4 is Cl. Table Row Heading
97B Q1 is 4-Me-Ph, R2 is Me and R4 is H.
98B Q1 is 4-Me-Ph, R2 is Cl and R4 is H.
99B Q1 is 4-Me-Ph, R2 is Br and R4 is H.
IOOB Q1 is 3-Me-Ph, R2 is Cl and R4 is Me.
101B Q1 is 3-Me-Ph, R2 is Cl and R4 is CFH2.
102B Q1 is 3-Me-Ph, R2 is Br and R4 is Me.
103B Q1 is 3-Me-Ph, R2 is I and R4 is Me.
104B Q1 is 3-Me-Ph, R2 is Me and R4 is Me.
105B Q1 is 3-Me-Ph, R2 is Me and R4 is Cl.
106B Q1 is 3-Me-Ph, R2 is Me and R4 is Br.
107B Q1 is 3-Me-Ph, R2 is Me and R4 is I.
108B Q1 is 3-Me-Ph, R2 is Br and R4 is Br.
109B Q1 is 3-Me-Ph, R2 is Br and R4 is Cl.
HOB Q1 is 3-Me-Ph, R2 is Cl and R4 is Br. urn Q1 is 3-Me-Ph, R2 is Cl and R4 is Cl.
112B Q1 is 3-Me-Ph, R2 is Me and R4 is H.
113B Q1 is 3-Me-Ph, R2 is Cl and R4 is H.
114B Q1 is 3-Me-Ph, R2 is Br and R4 is H.
115B Q1 is 4-Et-Ph, R2 is Cl and R4 is Me.
116B Q1 is 4-Et-Ph, R2 is Cl and R4 is CFH2.
117B Q1 is 4-Et-Ph, R2 is Br and R4 is Me.
118B Q1 is 4-Et-Ph, R2 is I and R4 is Me.
119B Q1 is 4-Et-Ph, R2 is Me and R4 is Me.
120B Q1 is 4-Et-Ph, R2 is Me and R4 is Cl.
121B Q1 is 4-Et-Ph, R2 is Me and R4 is Br.
122B Q1 is 4-Et-Ph, R2 is Me and R4 is I.
123B Q1 is 4-Et-Ph, R2 is Br and R4 is Br.
124B Q1 is 4-Et-Ph, R2 is Br and R4 is Cl.
125B Q1 is 4-Et-Ph, R2 is Cl and R4 is Br.
126B Q1 is 4-Et-Ph, R2 is Cl and R4 is Cl.
127B Q1 is 4-Et-Ph, R2 is Me and R4 is H.
128B Q1 is 4-Et-Ph, R2 is Cl and R4 is H.
129B Q1 is 4-Et-Ph, R2 is Br and R4 is H.
13OB Q1 is 4-Cl, 3-F-Ph, R2 is Cl and R4 is Me.
131B Q1 is 4-Cl, 3-F-Ph, R2 is Cl and R4 is CFH2.
132B Q1 is 4-Cl, 3-F-Ph, R2 is Br and R4 is Me.
133B Q1 is 4-Cl, 3-F-Ph, R2 is I and R4 is Me. Table Row Heading
134B Q1 is 4-Cl, 3-F-Ph, R2 is Me and R4 is Me.
135B Q1 is 4-Cl, 3-F-Ph, R2 is Me and R4 is Cl.
136B Q1 is 4-Cl, 3-F-Ph, R2 is Me and R4 is Br.
137B Q1 is 4-Cl, 3-F-Ph, R2 is Me and R4 is I.
138B Q1 is 4-Cl, 3-F-Ph, R2 is Br and R4 is Br.
139B Q1 is 4-Cl, 3-F-Ph, R2 is Br and R4 is Cl.
140B Q1 is 4-Cl, 3-F-Ph, R2 is Cl and R4 is Br.
141B Q1 is 4-Cl, 3-F-Ph, R2 is Cl and R4 is Cl.
142B Q1 is 4-Cl, 3-F-Ph, R2 is Me and R4 is H.
143B Q1 is 4-Cl, 3-F-Ph R2 is Cl and R4 is H.
144B Q1 is 4-Cl, 3-F-Ph, R2 is Br and R4 is H.
145B Q1 is 2-Cl, 4-F-Ph, R2 is Cl and R4 is Me.
146B Q1 is 2-Cl, 4-F-Ph, R2 is Cl and R4 is CFH2.
147B Q1 is 2-Cl, 4-F-Ph, R2 is Br and R4 is Me.
148B Q1 is 2-Cl, 4-F-Ph, R2 is I and R4 is Me.
149B Q1 is 2-Cl, 4-F-Ph, R2 is Me and R4 is Me.
150B Q1 is 2-Cl, 4-F-Ph, R2 is Me and R4 is Cl.
151B Q1 is 2-Cl, 4-F-Ph, R2 is Me and R4 is Br.
152B Q1 is 2-Cl, 4-F-Ph, R2 is Me and R4 is I.
153B Q1 is 2-Cl, 4-F-Ph, R2 is Br and R4 is Br.
154B Q1 is 2-Cl, 4-F-Ph, R2 is Br and R4 is Cl.
155B Q1 is 2-Cl, 4-F-Ph, R2 is Cl and R4 is Br.
156B Q1 is 2-Cl, 4-F-Ph, R2 is Cl and R4 is Cl.
157B Q1 is 2-Cl, 4-F-Ph, R2 is Me and R4 is H.
158B Q1 is 2-Cl, 4-F-Ph, R2 is Cl and R4 is H.
159B Q1 is 2-Cl, 4-F-Ph, R2 is Br and R4 is H.
160B Q1 is 4-F, 3-Me-Ph, R2 is Cl and R4 is Me.
161B Q1 is 4-F, 3-Me-Ph, R2 is Cl and R4 is CFH2.
162B Q1 is 4-F, 3-Me-Ph, R2 is Br and R4 is Me.
163B Q1 is 4-F, 3-Me-Ph, R2 is I and R4 is Me.
164B Q1 is 4-F, 3-Me-Ph, R2 is Me and R4 is Me.
165B Q1 is 4-F, 3-Me-Ph, R2 is Me and R4 is Cl.
166B Q1 is 4-F, 3-Me-Ph, R2 is Me and R4 is Br.
167B Q1 is 4-F, 3-Me-Ph, R2 is Me and R4 is I.
168B Q1 is 4-F, 3-Me-Ph, R2 is Br and R4 is Br.
169B Q1 is 4-F, 3-Me-Ph, R2 is Br and R4 is Cl.
170B Q1 is 4-F, 3-Me-Ph, R2 is Cl and R4 is Br. Table Row Heading
171B Q1 is 4-F, 3-Me-Ph, R2 is Cl and R4 is Cl.
172B Q1 is 4-F, 3-Me-Ph, R2 is Me and R4 is H.
173B Q1 is 4-F, 3-Me-Ph, R2 is Cl and R4 is H.
174B Q1 is 4-F, 3-Me-Ph, R2 is Br and R4 is H.
175B Q1 is 3,4-di-F-Ph, R2 is Cl and R4 is Me.
176B Q1 is 3,4-di-F-Ph, R2 is Cl and R4 is CFH2.
177B Q1 is 3,4-di-F-Ph, R2 is Br and R4 is Me.
178B Q1 is 3,4-di-F-Ph, R2 is I and R4 is Me.
179B Q1 is 3,4-di-F-Ph, R2 is Me and R4 is Me.
180B Q1 is 3,4-di-F-Ph, R2 is Me and R4 is Cl.
181B Q1 is 3,4-di-F-Ph, R2 is Me and R4 is Br.
182B Q1 is 3,4-di-F-Ph, R2 is Me and R4 is I.
183B Q1 is 3,4-di-F-Ph, R2 is Br and R4 is Br.
184B Q1 is 3,4-di-F-Ph, R2 is Br and R4 is Cl.
185B Q1 is 3,4-di-F-Ph, R2 is Cl and R4 is Br.
186B Q1 is 3,4-di-F-Ph, R2 is Cl and R4 is Cl.
187B Q1 is 3,4-di-F-Ph, R2 is Me and R4 is H.
188B Q1 is 3,4-di-F-Ph, R2 is Cl and R4 is H.
189B Q1 is 3,4-di-F-Ph, R2 is Br and R4 is H.
190B Q1 is 3,4-di-Cl-Ph, R2 is Cl and R4 is Me.
191B Q1 is 3,4-di-Cl-Ph, R2 is Cl and R4 is CFH2.
192B Q1 is 3,4-di-Cl-Ph, R2 is Br and R4 is Me.
193B Q1 is 3,4-di-Cl-Ph, R2 is I and R4 is Me.
194B Q1 is 3,4-di-Cl-Ph, R2 is Me and R4 is Me.
195B Q1 is 3,4-di-Cl-Ph, R2 is Me and R4 is Cl.
196B Q1 is 3,4-di-Cl-Ph, R2 is Me and R4 is Br.
197B Q1 is 3,4-di-Cl-Ph, R2 is Me and R4 is I.
198B Q1 is 3,4-di-Cl-Ph, R2 is Br and R4 is Br.
199B Q1 is 3,4-di-Cl-Ph, R2 is Br and R4 is Cl.
200B Q1 is 3,4-di-Cl-Ph, R2 is Cl and R4 is Br.
201B Q1 is 3,4-di-Cl-Ph, R2 is Cl and R4 is Cl.
202B Q1 is 3,4-di-Cl-Ph, R2 is Me and R4 is H.
203B Q1 is 3,4-di-Cl-Ph, R2 is Cl and R4 is H.
204B Q1 is 3,4-di-Cl-Ph, R2 is Br and R4 is H.
205B Q1 is 3,5-di-MeO-Ph, R2 is Cl and R4 is Me.
206B Q1 is 3,5-di-MeO-Ph, R2 is Cl and R4 is CFH2.
207B Q1 is 3,5-di-MeO-Ph, R2 is Br and R4 is Me. Table Row Heading
208B Q1 is 3,5-di-MeO-Ph, R2 is I and R4 is Me.
209B Q1 is 3,5-di-MeO-Ph, R2 is Me and R4 is Me.
210B Q1 is 3,5-di-MeO-Ph, R2 is Me and R4 is Cl.
211B Q1 is 3,5-di-MeO-Ph, R2 is Me and R4 is Br.
212B Q1 is 3,5-di-MeO-Ph, R2 is Me and R4 is I.
213B Q1 is 3,5-di-MeO-Ph, R2 is Br and R4 is Br.
214B Q1 is 3,5-di-MeO-Ph, R2 is Br and R4 is Cl.
215B Q1 is 3,5-di-MeO-Ph, R2 is Cl and R4 is Br.
216B Q1 is 3,5-di-MeO-Ph, R2 is Cl and R4 is Cl.
217B Q1 is 3,5-di-MeO-Ph, R2 is Me and R4 is H.
218B Q1 is 3,5-di-MeO-Ph, R2 is Cl and R4 is H.
219B Q1 is 3,5-di-MeO-Ph, R2 is Br and R4 is H.
220B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is Me.
221B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is CFH2.
222B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is Me.
223B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is I and R4 is Me.
224B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is Me.
225B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is Cl.
226B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is Br.
227B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is I.
228B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is Br.
229B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is Cl.
230B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is Br.
231B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is Cl.
232B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is H.
233B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is H.
234B Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is H.
235B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is Me.
236B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is CFH2.
237B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is Me.
238B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is I and R4 is Me.
239B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is Me.
240B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is Cl.
241B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is Br.
242B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is I.
243B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is Br.
244B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is Cl. Table Row Heading
245B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is Br.
246B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is Cl.
247B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Me and R4 is H.
248B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Cl and R4 is H.
249B Q1 is 4-Cl, 3,5-di-MeO-Ph, R2 is Br and R4 is H.
250B Q1 is 4-Cl-Bn, R2 is Cl and R4 is Me.
251B Q1 is 4-Cl-Bn, R2 is Cl and R4 is CFH2.
252B Q1 is 4-Cl-Bn, R2 is Br and R4 is Me.
253B Q1 is 4-Cl-Bn, R2 is I and R4 is Me.
254B Q1 is 4-Cl-Bn, R2 is Me and R4 is Me.
255B Q1 is 4-Cl-Bn, R2 is Me and R4 is Cl.
256B Q1 is 4-Cl-Bn, R2 is Me and R4 is Br.
257B Q1 is 4-Cl-Bn, R2 is Me and R4 is I.
258B Q1 is 4-Cl-Bn, R2 is Br and R4 is Br.
259B Q1 is 4-Cl-Bn, R2 is Br and R4 is Cl.
260B Q1 is 4-Cl-Bn, R2 is Cl and R4 is Br.
261B Q1 is 4-Cl-Bn, R2 is Cl and R4 is Cl.
262B Q1 is 4-Cl-Bn, R2 is Me and R4 is H.
263B Q1 is 4-Cl-Bn, R2 is Cl and R4 is H.
264B Q1 is 4-Cl-Bn, R2 is Br and R4 is H.
265B Q1 is 4-F-Bn, R2 is Cl and R4 is Me.
266B Q1 is 4-F-Bn, R2 is Cl and R4 is CFH2.
267B Q1 is 4-F-Bn, R2 is Br and R4 is Me.
268B Q1 is 4-F-Bn, R2 is I and R4 is Me.
269B Q1 is 4-F-Bn, R2 is Me and R4 is Me.
270B Q1 is 4-F-Bn, R2 is Me and R4 is Cl.
271B Q1 is 4-F-Bn, R2 is Me and R4 is Br.
272B Q1 is 4-F-Bn, R2 is Me and R4 is I.
273B Q1 is 4-F-Bn, R2 is Br and R4 is Br.
274B Q1 is 4-F-Bn, R2 is Br and R4 is Cl.
275B Q1 is 4-F-Bn, R2 is Cl and R4 is Br.
276B Q1 is 4-F-Bn, R2 is Cl and R4 is Cl.
277B Q1 is 4-F-Bn, R2 is Me and R4 is H.
278B Q1 is 4-F-Bn, R2 is Cl and R4 is H.
279B Q1 is 4-F-Bn, R2 is Br and R4 is H.
280B Q1 is 6-Cl-3-pyridinyl, R2 is Cl and R4 is Me.
281B Q1 is 6-Cl-3-pyridinyl, R2 is Cl and R4 is CFH2. Table Row Heading
282B Q1 is 6-Cl-3-pyridinyl, R2 is Br and R4 is Me.
283B Q1 is 6-Cl-3-pyridinyl, R2 is I and R4 is Me.
284B Q1 is 6-Cl-3-pyridinyl, R2 is Me and R4 is Me.
285B Q1 is 6-Cl-3-pyridinyl, R2 is Me and R4 is Cl.
286B Q1 is 6-Cl-3-pyridinyl, R2 is Me and R4 is Br.
287B Q1 is 6-Cl-3-pyridinyl, R2 is Me and R4 is I.
288B Q1 is 6-Cl-3-pyridinyl, R2 is Me and R4 is MeO.
289B Q1 is 6-Cl-3-pyridinyl, R2 is MeO and R4 is Me.
290B Q1 is 6-Cl-3-pyridinyl, R2 is Br and R4 is Br.
291B Q1 is 6-Cl-3-pyridinyl, R2 is Br and R4 is Cl.
292B Q1 is 6-Cl-3-pyridinyl, R2 is Cl and R4 is Br.
293B Q1 is 6-Cl-3-pyridinyl, R2 is Cl and R4 is Cl.
294B Q1 is 6-Cl-3-pyridinyl, R2 is Me and R4 is MeS.
295B Q1 is 6-Cl-3-pyridinyl, R2 is MeS and R4 is Me.
296B Q1 is 6-Cl-3-pyridinyl, R2 is Et and R4 is Br.
297B Q1 is 6-Cl-3-pyridinyl, R2 is Et and R4 is Cl.
298B Q1 is 6-Cl-3-pyridinyl, R2 is Et and R4 is Me.
299B Q1 is 6-Cl-3-pyridinyl, R2 is Me and R4 is Et.
300B Q1 is 6-Cl-3-pyridinyl, R2 is Cl and R4 is Et.
301B Q1 is 6-Cl-3-pyridinyl, R2 is Me and R4 is CN.
302B Q1 is 6-Cl-3-pyridinyl, R2 is Me and R4 is H.
303B Q1 is 6-Cl-3-pyridinyl, R2 is Cl and R4 is H.
304B Q1 is 6-Cl-3-pyridinyl, R2 is Br and R4 is H.
305B Q1 is 6-Me-3-pyridinyl, R2 is Cl and R4 is Me.
306B Q1 is 6-Me-3-pyridinyl, R2 is Cl and R4 is CFH2.
307B Q1 is 6-Me-3-pyridinyl, R2 is Br and R4 is Me.
308B Q1 is 6-Me-3-pyridinyl, R2 is I and R4 is Me.
309B Q1 is 6-Me-3-pyridinyl, R2 is Me and R4 is Me.
310B Q1 is 6-Me-3-pyridinyl, R2 is Me and R4 is Cl.
311B Q1 is 6-Me-3-pyridinyl, R2 is Me and R4 is Br.
312B Q1 is 6-Me-3-pyridinyl, R2 is Me and R4 is I.
313B Q1 is 6-Me-3-pyridinyl, R2 is Br and R4 is Br.
314B Q1 is 6-Me-3-pyridinyl, R2 is Br and R4 is Cl.
315B Q1 is 6-Me-3-pyridinyl, R2 is Cl and R4 is Br.
316B Q1 is 6-Me-3-pyridinyl, R2 is Cl and R4 is Cl.
317B Q1 is 6-Me-3-pyridinyl, R2 is Me and R4 is H.
318B Q1 is 6-Me-3-pyridinyl, R2 is Cl and R4 is H. Table Row Heading
319B Q1 is 6-Me-3-pyridinyl, R2 i s Br and R4 is H.
320B Q1 is 6-MeO-3-pyridinyl, R2 is Cl and R4 is Me.
321B Q1 is 6-MeO-3-pyridinyl, R2 is Cl and R4 is CFH2.
322B Q1 is 6-MeO-3-pyridinyl, R2 is Br and R4 is Me.
323B Q1 is 6-MeO-3-pyridinyl, R2 is I and R4 is Me.
324B Q1 is 6-MeO-3-pyridinyl, R2 is Me and R4 is Me.
325B Q1 is 6-MeO-3-pyridinyl, R2 is Me and R4 is Cl.
326B Q1 is 6-MeO-3-pyridinyl, R2 is Me and R4 is Br.
327B Q1 is 6-MeO-3-pyridinyl, R2 is Me and R4 is I.
328B Q1 is 6-MeO-3-pyridinyl, R2 is Br and R4 is Br.
329B Q1 is 6-MeO-3-pyridinyl, R2 is Br and R4 is Cl.
330B Q1 is 6-MeO-3-pyridinyl, R2 is Cl and R4 is Br.
331B Q1 is 6-MeO-3-pyridinyl, R2 is Cl and R4 is Cl.
332B Q1 is 6-MeO-3-pyridinyl, R2 is Me and R4 is H.
333B Q1 is 6-MeO-3-pyridinyl, R2 is Cl and R4 is H.
334B Q1 is 6-MeO-3-pyridinyl, R2 is Br and R4 is H.
335B Q1 is 6-CF3-3-pyridinyl, R2 is Cl and R4 is Me.
336B Q1 is 6-CF3-3-pyridinyl, R2 is Cl and R4 is CFH2.
337B Q1 is 6-CF3-3-pyridinyl, R2 is Br and R4 is Me.
338B Q1 is 6-CF3-3-pyridinyl, R2 is I and R4 is Me.
339B Q1 is 6-CF3-3-pyridinyl, R2 is Me and R4 is Me.
340B Q1 is 6-CF3-3-pyridinyl, R2 is Me and R4 is Cl.
341B Q1 is 6-CF3-3-pyridinyl, R2 is Me and R4 is Br.
342B Q1 is 6-CF3-3-pyridinyl, R2 is Me and R4 is I.
343B Q1 is 6-CF3-3-pyridinyl, R2 is Br and R4 is Br.
344B Q1 is 6-CF3-3-pyridinyl, R2 is Br and R4 is Cl.
345B Q1 is 6-CF3-3-pyridinyl, R2 is Cl and R4 is Br.
346B Q1 is 6-CF3-3-pyridinyl, R2 is Cl and R4 is Cl.
347B Q1 is 6-CF3-3-pyridinyl, R2 is Me and R4 is H.
348B Q1 is 6-CF3-3-pyridinyl, R2 is Cl and R4 is H.
349B Q1 is 6-CF3-3-pyridinyl, R2 is Br and R4 is H.
350B Q1 is 6-Br-3-pyridinyl, R2 is Cl and R4 is Me.
351B Q1 is 6-Br-3-pyridinyl, R2 is Cl and R4 is CFH2.
352B Q1 is 6-Br-3-pyridinyl, R2 is Br and R4 is Me.
353B Q1 is 6-Br-3-pyridinyl, R2 is I and R4 is Me.
354B Q1 is 6-Br-3-pyridinyl, R2 is Me and R4 is Me.
355B Q1 is 6-Br-3-pyridinyl, R2 is Me and R4 is Cl. Table Row Heading
356B Q1 is 6-Br-3-pyridinyl, R2 is Me and R4 is Br.
357B Q1 is 6-Br-3-pyridinyl, R2 is Me and R4 is I.
358B Q1 is 6-Br-3-pyridinyl, R2 is Br and R4 is Br.
359B Q1 is 6-Br-3-pyridinyl, R2 is Br and R4 is Cl.
360B Q1 is 6-Br-3-pyridinyl, R2 is Cl and R4 is Br.
361B Q1 is 6-Br-3-pyridinyl, R2 is Cl and R4 is Cl.
362B Q1 is 6-Br-3-pyridinyl, R2 is Me and R4 is H.
363B Q1 is 6-Br-3-pyridinyl, R2 is Cl and R4 is H.
364B Q1 is 6-Br-3-pyridinyl, R2 is Br and R4 is H.
365B Q1 is 6-F-3-pyridinyl, R2 is Cl and R4 is Me.
366B Q1 is 6-F-3-pyridinyl, R2 is Cl and R4 is CFH2.
367B Q1 is 6-F-3-pyridinyl, R2 is Br and R4 is Me.
368B Q1 is 6-F-3-pyridinyl, R2 is I and R4 is Me.
369B Q1 is 6-F-3-pyridinyl, R2 is Me and R4 is Me.
370B Q1 is 6-F-3-pyridinyl, R2 is Me and R4 is Cl.
371B Q1 is 6-F-3-pyridinyl, R2 is Me and R4 is Br.
372B Q1 is 6-F-3-pyridinyl, R2 is Me and R4 is I.
373B Q1 is 6-F-3-pyridinyl, R2 is Br and R4 is Br.
374B Q1 is 6-F-3-pyridinyl, R2 is Br and R4 is Cl.
375B Q1 is 6-F-3-pyridinyl, R2 is Cl and R4 is Br.
376B Q1 is 6-F-3-pyridinyl, R2 is Cl and R4 is Cl.
377B Q1 is 6-F-3-pyridinyl, R2 is Me and R4 is H.
378B Q1 is 6-F-3-pyridinyl, R2 is Cl and R4 is H.
379B Q1 is 6-F-3-pyridinyl, R2 is Br and R4 is H.
380B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is Cl and R4 is Me.
381B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is Cl and R4 is CFH2.
382B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is Br and R4 is Me.
383B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is I and R4 is Me.
384B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is Me and R4 is Me.
385B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is Me and R4 is Cl.
386B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is Me and R4 is Br.
387B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is Me and R4 is I.
388B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is Br and R4 is Br.
389B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is Br and R4 is Cl.
390B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is Cl and R4 is Br.
391B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is Cl and R4 is Cl.
392B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is Me and R4 is H. Table Row Heading
393B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is i Cl and R4 is H.
394B Q1 is 2-Cl, 6-Me-4-pyridinyl, R2 is i Br and R4 is H.
395B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Cl and R4 is Me.
396B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Cl and R4 is CFH2.
397B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Br and R4 is Me.
398B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is I and R4 is Me.
399B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Me and R4 is Me.
400B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Me and R4 is Cl.
401B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Me and R4 is Br.
402B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Me and R4 is I.
403B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Br and R4 is Br.
404B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Br and R4 is Cl.
405B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Cl and R4 is Br.
406B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Cl and R4 is Cl.
407B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Me and R4 is H.
408B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Cl and R4 is H.
409B Q1 is 2-Cl, 6-MeO-3-pyridinyl, R2 is Br and R4 is H.
410B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Cl and R4 is Me.
411B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Cl and R4 is CFH2.
412B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Br and R4 is Me.
413B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is I and R4 is Me.
414B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Me and R4 is Me.
415B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Me and R4 is Cl.
416B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Me and R4 is Br.
417B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Me and R4 is I.
418B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Br and R4 is Br.
419B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Br and R4 is Cl.
420B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Cl and R4 is Br.
421B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Cl and R4 is Cl.
422B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Me and R4 is H.
423B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Cl and R4 is H.
424B Q1 is 2-Cl, 6-CF3-3-pyridinyl, R2 is Br and R4 is H.
425B Q1 is 5-Cl-3-pyridinyl, R2 is Cl and R4 is Me.
426B Q1 is 5-Cl-3-pyridinyl, R2 is Cl and R4 is CFH2.
427B Q1 is 5-Cl-3-pyridinyl, R2 is Br and R4 is Me.
428B Q1 is 5-Cl-3-pyridinyl, R2 is I and R4 is Me.
429B Q1 is 5-Cl-3-pyridinyl, R2 is Me and R4 is Me. Table Row Heading
430B Q1 is 5-Cl-3-pyridinyl, R2 is Me and R4 is Cl. 431B Q1 is 5-Cl-3-pyridinyl, R2 is Me and R4 is Br. 432B Q1 is 5-Cl-3-pyridinyl, R2 is Me and R4 is I. 433B Q1 is 5-Cl-3-pyridinyl, R2 is Br and R4 is Br. 434B Q1 is 5-Cl-3-pyridinyl, R2 is Br and R4 is Cl. 435B Q1 is 5-Cl-3-pyridinyl, R2 is Cl and R4 is Br. 436B Q1 is 5-Cl-3-pyridinyl, R2 is Cl and R4 is Cl. 437B Q1 is 5-Cl-3-pyridinyl, R2 is Me and R4 is H. 438B Q1 is 5-Cl-3-pyridinyl, R2 is Cl and R4 is H. 439B Q1 is 5-Cl-3-pyridinyl, R2 is Br and R4 is H. 44OB Q1 is 5-F-3-pyridinyl, R2 is Cl and R4 is Me. 441B Q1 is 5-F-3-pyridinyl, R2 is Cl and R4 is CFH2. 442B Cr is 5-F-3-pyridinyl, R2 is Br and R4 is Me. 443B Cr is 5-F-3-pyridinyl, R2 is I and R4 is Me. 444B Cr is 5-F-3-pyridinyl, R2 is Me and R4 is Me. 445B Q1 is 5-F-3-pyridinyl, R2 is Me and R4 is Cl. 446B Q1 is 5-F-3-pyridinyl, R2 is Me and R4 is Br. 447B QI is 5-F-3-pyridinyl, R2 is Me and R4 is I. 448B Q1 is 5-F-3-pyridinyl, R2 is Br and R4 is Br. 449B Q1 is 5-F-3-pyridinyl, R2 is Br and R4 is Cl. 450B Q1 is 5-F-3-pyridinyl, R2 is Cl and R4 is Br. 451B Q1 is 5-F-3-pyridinyl, R2 is Cl and R4 is Cl. 452B Q1 is 5-F-3-pyridinyl, R2 is Me and R4 is H. 453B Q1 is 5-F-3-pyridinyl, R2 is Cl and R4 is H. 454B Q1 is 5-F-3-pyridinyl, R2 is Br and R4 is H. 455B Q1 is 5-Me-3-pyridinyl, R2 is Cl and R4 is Me. 456B Q1 is 5-Me-3-pyridinyl, R2 is Cl and R4 is CFH2. 457B QI is 5-Me-3-pyridinyl, R2 is Br and R4 is Me. 458B Cr is 5-Me-3-pyridinyl, R2 is I and R4 is Me. 459B QI is 5-Me-3-pyridinyl, R2 is Me and R4 is Me. 460B Q1 is 5-Me-3-pyridinyl, R2 is Me and R4 is Cl. 461B QI is 5-Me-3-pyridinyl, R2 is Me and R4 is Br. 462B Cr is 5-Me-3-pyridinyl, R2 is Me and R4 is I. 463B Q1 is 5-Me-3-pyridinyl, R2 is Br and R4 is Br. 464B Q1 is 5-Me-3-pyridinyl, R2 is Br and R4 is Cl. 465B Q1 is 5-Me-3-pyridinyl, R2 is Cl and R4 is Br. 466B Q1 is 5-Me-3-pyridinyl, R2 is Cl and R4 is Cl. Table Row Heading
467B Q1 is 5-Me-3-pyridinyl, R2 is Me and R4 is H.
468B Q1 is 5-Me-3-pyridinyl, R2 is Cl and R4 is H.
469B Q1 is 5-Me-3-pyridinyl, R2 is Br and R4 is H.
470B Q1 is 5-MeO-3-pyridinyl, R2 is Cl and R4 is Me.
471B Q1 is 5-MeO-3-pyridinyl, R2 is Cl and R4 is CFH2.
472B Q1 is 5-MeO-3-pyridinyl, R2 is Br and R4 is Me.
473B Q1 is 5-MeO-3-pyridinyl, R2 is I and R4 is Me.
474B Q1 is 5-MeO-3-pyridinyl, R2 is Me and R4 is Me.
475B Q1 is 5-MeO-3-pyridinyl, R2 is Me and R4 is Cl.
476B Q1 is 5-MeO-3-pyridinyl, R2 is Me and R4 is Br.
477B Q1 is 5-MeO-3-pyridinyl, R2 is Me and R4 is I.
478B Q1 is 5-MeO-3-pyridinyl, R2 is Br and R4 is Br.
479B Q1 is 5-MeO-3-pyridinyl, R2 is Br and R4 is Cl.
480B Q1 is 5-MeO-3-pyridinyl, R2 is Cl and R4 is Br.
481B Q1 is 5-MeO-3-pyridinyl, R2 is Cl and R4 is Cl.
482B Q1 is 5-MeO-3-pyridinyl, R2 is Me and R4 is H.
483B Q1 is 5-MeO-3-pyridinyl, R2 is Cl and R4 is H.
484B Q1 is 5-MeO-3-pyridinyl, R2 is Br and R4 is H.
485B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Cl and R4 is Me.
486B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Cl and R4 is CFH2.
487B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Br and R4 is Me.
488B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is I and R4 is Me.
489B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Me and R4 is Me.
490B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Me and R4 is Cl.
491B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Me and R4 is Br.
492B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Me and R4 is I.
493B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Br and R4 is Br.
494B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Br and R4 is Cl.
495B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Cl and R4 is Br.
496B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Cl and R4 is Cl.
497B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Me and R4 is H.
498B Q1 is 6-Cl, 5-MeO-3-pyridinyl, R2 is Cl and R4 is H.
499B Q1 is 6-Cl- 5-MeO-3-pyridinyl, R2 is Br and R4 is H.
500B Q1 is 6-Cl-3-pyridazinyl, R2 is Cl and R4 is Me.
501B Q1 is 6-Cl-3-pyridazinyl, R2 is Cl and R4 is CFH2.
502B Q1 is 6-Cl-3-pyridazinyl, R2 is Br and R4 is Me.
503B Q1 is 6-Cl-3-pyridazinyl, R2 is I and R4 is Me. Table Row Heading
504B QMs 6-Cl-3-pyridazinyl, R2 is Me and R4 is Me. 505B Q1 is 6-Cl-3-pyridazinyl, R2 is Me and R4 is Cl. 506B QMs 6-Cl-3-pyridazinyl, R2 is Me and R4 is Br. 507B QMs 6-Cl-3-pyridazinyl, R2 is Me and R4 is I. 508B Q1 is 6-Cl-3-pyridazinyl, R2 is Br and R4 is Br. 509B Q1 is 6-Cl-3-pyridazinyl, R2 is Br and R4 is Cl. 510B Q1 is 6-Cl-3-pyridazinyl, R2 is Cl and R4 is Br. 511B Q1 is 6-Cl-3-pyridazinyl, R2 is Cl and R4 is Cl. 512B Q1 is 6-Cl-3-pyridazinyl, R2 is Me and R4 is H. 513B Q1 is 6-Cl-3-pyridazinyl, R2 is Cl and R4 is H. 514B Q1 is 6-Cl-3-pyridazinyl, R2 is Br and R4 is H. 515B QMs 6-Me-3-pyridazinyl, R2 is Cl and R4 is Me. 516B Q1 is 6-Me-3-pyridazinyl, R2 is Cl and R4 is CFH2. 517B QI is 6-Me-3-pyridazinyl, R2 is Br and R4 is Me. 518B QI is 6-Me-3-pyridazinyl, R2 is I and R4 is Me. 519B QMs 6-Me-3-pyridazinyl, R2 is Me and R4 is Me. 520B QMs 6-Me-3-pyridazinyl, R2 is Me and R4 is Cl. 521B QMs 6-Me-3-pyridazinyl, R2 is Me and R4 is Br. 522B QMs 6-Me-3-pyridazinyl, R2 is Me and R4 is I. 523B QMs 6-Me-3-pyridazinyl, R2 is Br and R4 is Br. 524B Q1 is 6-Me-3-pyridazinyl, R2 is Br and R4 is Cl. 525B Q1 is 6-Me-3-pyridazinyl, R2 is Cl and R4 is Br. 526B Q1 is 6-Me-3-pyridazinyl, R2 is Cl and R4 is Cl. 527B QMs 6-Me-3-pyridazinyl, R2 is Me and R4 is H. 528B Q1 is 6-Me-3-pyridazinyl, R2 is Cl and R4 is H. 529B QMs 6-Me-3-pyridazinyl, R2 is Br and R4 is H. 530B Q1 is 6-MeO-3-pyridazinyl, R2 is Cl and R4 is Me. 531B Q1 is 6-MeO-3-pyridazinyl, R2 is Cl and R4 is CFH2. 532B QI is 6-MeO-3-pyridazinyl, R2 is Br and R4 is Me. 533B QMs 6-MeO-3-pyridazinyl, R2 is I and R4 is Me. 534B QI is 6-MeO-3-pyridazinyl, R2 is Me and R4 is Me. 535B Q1 is 6-MeO-3-pyridazinyl, R2 is Me and R4 is Cl. 536B QMs 6-MeO-3-pyridazinyl, R2 is Me and R4 is Br. 537B QMs 6-MeO-3-pyridazinyl, R2 is Me and R4 is I. 538B QMs 6-MeO-3-pyridazinyl, R2 is Br and R4 is Br. 539B Q1 is 6-MeO-3-pyridazinyl, R2 is Br and R4 is Cl. 540B Q1 is 6-MeO-3-pyridazinyl, R2 is Cl and R4 is Br. Table Row Heading
541B Q1 is 6-MeO-3-pyridazinyl, R2 is Cl and R4 is Cl.
542B Q1 is 6-MeO-3-pyridazinyl, R2 is Me and R4 is H.
543B Q1 is 6-MeO-3-pyridazinyl, R2 is Cl and R4 is H.
544B Q1 is 6-MeO-3-pyridazinyl, R2 is Br and R4 is H.
545B Q1 is 6-CF3-3-pyridazinyl, R2 is Cl and R4 is Me.
546B Q1 is 6-CF3-3-pyridazinyl, R2 is Cl and R4 is CFH2.
547B Q1 is 6-CF3-3-pyridazinyl, R2 is Br and R4 is Me.
548B Q1 is 6-CF3-3-pyridazinyl, R2 is I and R4 is Me.
549B Q1 is 6-CF3-3-pyridazinyl, R2 is Me and R4 is Me.
550B Q1 is 6-CF3-3-pyridazinyl, R2 is Me and R4 is Cl.
551B Q1 is 6-CF3-3-pyridazinyl, R2 is Me and R4 is Br.
552B Q1 is 6-CF3-3-pyridazinyl, R2 is Me and R4 is I.
553B Q1 is 6-CF3-3-pyridazinyl, R2 is Br and R4 is Br.
554B Q1 is 6-CF3-3-pyridazinyl, R2 is Br and R4 is Cl.
555B Q1 is 6-CF3-3-pyridazinyl, R2 is Cl and R4 is Br.
556B Q1 is 6-CF3-3-pyridazinyl, R2 is Cl and R4 is Cl.
557B Q1 is 6-CF3-3-pyridazinyl, R2 is Me and R4 is H.
558B Q1 is 6-CF3-3-pyridazinyl, R2 is Cl and R4 is H.
559B Q1 is 6-CF3-3-pyridazinyl, R2 is Br and R4 is H.
560B Q1 is 5-Cl-3-pyridazinyl, R2 is Cl and R4 is Me.
561B Q1 is 5-Cl-3-pyridazinyl, R2 is Cl and R4 is CFH2.
562B Q1 is 5-Cl-3-pyridazinyl, R2 is Br and R4 is Me.
563B Q1 is 5-Cl-3-pyridazinyl, R2 is I and R4 is Me.
564B Q1 is 5-Cl-3-pyridazinyl, R2 is Me and R4 is Me.
565B Q1 is 5-Cl-3-pyridazinyl, R2 is Me and R4 is Cl.
566B Q1 is 5-Cl-3-pyridazinyl, R2 is Me and R4 is Br.
567B Q1 is 5-Cl-3-pyridazinyl, R2 is Me and R4 is I.
568B Q1 is 5-Cl-3-pyridazinyl, R2 is Br and R4 is Br.
569B Q1 is 5-Cl-3-pyridazinyl, R2 is Br and R4 is Cl.
570B Q1 is 5-Cl-3-pyridazinyl, R2 is Cl and R4 is Br.
571B Q1 is 5-Cl-3-pyridazinyl, R2 is Cl and R4 is Cl.
572B Q1 is 5-Cl-3-pyridazinyl, R2 is Me and R4 is H.
573B Q1 is 5-Cl-3-pyridazinyl, R2 is Cl and R4 is H.
574B Q1 is 5-Cl-3-pyridazinyl, R2 is Br and R4 is H.
575B Q1 is 5-F-3-pyridazinyl, R2 is Cl and R4 is Me.
576B Q1 is 5-F-3-pyridazinyl, R2 is Cl and R4 is CFH2.
577B Q1 is 5-F-3-pyridazinyl, R2 is '. 3r and R4 is Me. Table Row Heading
578B Q1 is 5-F-3-pyridazinyl, R2 is I and R4 is Me.
579B Q1 is 5-F-3-pyridazinyl, R2 is Me and R4 is Me.
580B Q1 is 5-F-3-pyridazinyl, R2 is Me and R4 is Cl.
581B Q1 is 5-F-3-pyridazinyl, R2 is Me and R4 is Br.
582B Q1 is 5-F-3-pyridazinyl, R2 is Me and R4 is I.
583B Q1 is 5-F-3-pyridazinyl, R2 is Br and R4 is Br.
584B Q1 is 5-F-3-pyridazinyl, R2 is Br and R4 is Cl.
585B Q1 is 5-F-3-pyridazinyl, R2 is Cl and R4 is Br.
586B Q1 is 5-F-3-pyridazinyl, R2 is Cl and R4 is Cl.
587B Q1 is 5-F-3-pyridazinyl, R2 is Me and R4 is H.
588B Q1 is 5-F-3-pyridazinyl, R2 is Cl and R4 is H.
589B Q1 is 5-F-3-pyridazinyl, R2 is Br and R4 is H.
590B Q1 is 5-MeO-3-pyridazinyl, R2 is Cl and R4 is Me.
591B Q1 is 5-MeO-3-pyridazinyl, R2 is Cl and R4 is CFH2.
592B Q1 is 5-MeO-3-pyridazinyl, R2 is Br and R4 is Me.
593B Q1 is 5-MeO-3-pyridazinyl, R2 is I and R4 is Me.
594B Q1 is 5-MeO-3-pyridazinyl, R2 is Me and R4 is Me.
595B Q1 is 5-MeO-3-pyridazinyl, R2 is Me and R4 is Cl.
596B Q1 is 5-MeO-3-pyridazinyl, R2 is Me and R4 is Br.
597B Q1 is 5-MeO-3-pyridazinyl, R2 is Me and R4 is I.
598B Q1 is 5-MeO-3-pyridazinyl, R2 is Br and R4 is Br.
599B Q1 is 5-MeO-3-pyridazinyl, R2 is Br and R4 is Cl.
600B Q1 is 5-MeO-3-pyridazinyl, R2 is Cl and R4 is Br.
601B Q1 is 5-MeO-3-pyridazinyl, R2 is Cl and R4 is Cl.
602B Q1 is 5-MeO-3-pyridazinyl, R2 is Me and R4 is H.
603B Q1 is 5-MeO-3-pyridazinyl, R2 is Cl and R4 is H.
604B Q1 is 5-MeO-3-pyridazinyl, R2 is Br and R4 is H.
605B Q1 is 2-Cl-5-pyrimidinyl, R2 is Cl and R4 is Me.
606B Q1 is 2-Cl-5-pyrimidinyl, R2 is Cl and R4 is CFH2.
607B Q1 is 2-Cl-5-pyrimidinyl, R2 is Br and R4 is Me.
608B Q1 is 2-Cl-5-pyrimidinyl, R2 is I and R4 is Me.
609B Q1 is 2-Cl-5-pyrimidinyl, R2 is Me and R4 is Me.
610B Q1 is 2-C1-5 pyrimidinyl, R2 is Me and R4 is Cl.
611B Q1 is 2-Cl-5-pyrimidinyl, R2 is Me and R4 is Br.
612B Q1 is 2-C1-5 -pyrimidinyl, R2 is Me and R4 is I.
613B Q1 is 2-Cl-5-pyrimidinyl, R2 is Br and R4 is Br.
614B Q1 is 2-C1-5 -pyrimidinyl, R2 is Br and R4 is Cl. Table Row Heading
615B Q1 is 2-Cl-5-pyrimidinyl, R2 is Cl and R4 is Br.
616B Q1 is 2-Cl-5-pyrimidinyl, R2 is Cl and R4 is Cl.
617B Q1 is 2-Cl-5-pyrimidinyl, R2 is Me and R4 is H.
618B Q1 is 2-Cl-5-pyrimidinyl, R2 is Cl and R4 is H.
619B Q1 is 2-Cl-5-pyrimidinyl, R2 is Br and R4 is H.
620B Q1 is 2-Me-5-pyrimidinyl, R2 is Cl and R4 is Me.
621B Q1 is 2-Me-5-pyrimidinyl, R2 is Cl and R4 is CFH2.
622B Q1 is 2-Me-5-pyrimidinyl, R2 is Br and R4 is Me.
623B Q1 is 2-Me-5-pyrimidinyl, R2 is I and R4 is Me.
624B Q1 is 2-Me-5-pyrimidinyl, R2 is Me and R4 is Me.
625B Q1 is 2-Me-5-pyrimidinyl, R2 is Me and R4 is Cl.
626B Q1 is 2-Me-5-pyrimidinyl, R2 is Me and R4 is Br.
627B Q1 is 2-Me-5-pyrimidinyl, R2 is Me and R4 is I.
628B Q1 is 2-Me-5-pyrimidinyl, R2 is Br and R4 is Br.
629B Q1 is 2-Me-5-pyrimidinyl, R2 is Br and R4 is Cl.
630B Q1 is 2-Me-5-pyrimidinyl, R2 is Cl and R4 is Br.
631B Q1 is 2-Me-5-pyrimidinyl, R2 is Cl and R4 is Cl.
632B Q1 is 2-Me-5-pyrimidinyl, R2 is Me and R4 is H.
633B Q1 is 2-Me-5-pyrimidinyl, R2 is Cl and R4 is H.
634B Q1 is 2-Me-5-pyrimidinyl, R2 is Br and R4 is H.
635B Q1 is 2-MeO-5-pyrimidinyl, R2 is Cl and R4 is Me.
636B Q1 is 2-MeO-5-pyrimidinyl, R2 is Cl and R4 is CFH2.
637B Q1 is 2-MeO-5-pyrimidinyl, R2 is Br and R4 is Me.
638B Q1 is 2-MeO-5-pyrimidinyl, R2 is I and R4 is Me.
639B Q1 is 2-MeO-5-pyrimidinyl, R2 is Me and R4 is Me.
640B Q1 is 2-MeO-5-pyrimidinyl, R2 is Me and R4 is Cl.
641B Q1 is 2-MeO-5-pyrimidinyl, R2 is Me and R4 is Br.
642B Q1 is 2-MeO-5-pyrimidinyl, R2 is Me and R4 is I.
643B Q1 is 2-MeO-5 pyrimidinyl, R2 is Br and R4 is Br.
644B Q1 is 2-MeO-5-pyrimidinyl, R2 is Br and R4 is Cl.
645B Q1 is 2-MeO-5-pyrimidinyl, R2 is Cl and R4 is Br.
646B Q1 is 2-MeO-5-pyrimidinyl, R2 is Cl and R4 is Cl.
647B Q1 is 2-MeO-5-pyrimidinyl, R2 is Me and R4 is H.
648B Q1 is 2-MeO-5-pyrimidinyl, R2 is Cl and R4 is H.
649B Q1 is 2-MeO-5-pyrimidinyl, R2 is Br and R4 is H.
650B Q1 is 2-CF3-5-pyrimidinyl, R2 is Cl and R4 is Me.
651B Q1 is 2-CF3-5-pyrimidinyl, R2 is Cl and R4 is CFH2. Table Row Heading
652B Q1 is 2-CF3-5-pyrimidinyl, R2 is Br and R4 is Me.
653B Q1 is 2-CF3-5-pyrimidinyl, R2 is I and R4 is Me.
654B Q1 is 2-CF3-5-pyrimidinyl, R2 is Me and R4 is Me.
655B Q1 is 2-CF3-5-pyrimidinyl, R2 is Me and R4 is Cl.
656B Q1 is 2-CF3-5-pyrimidinyl, R2 is Me and R4 is Br.
657B Q1 is 2-CF3-5-pyrimidinyl, R2 is Me and R4 is I.
658B Q1 is 2-CF3-5-pyrimidinyl, R2 is Br and R4 is Br.
659B Q1 is 2-CF3-5-pyrimidinyl, R2 is Br and R4 is Cl.
660B Q1 is 2-CF3-5-pyrimidinyl, R2 is Cl and R4 is Br.
661B Q1 is 2-CF3-5-pyrimidinyl, R2 is Cl and R4 is Cl.
662B Q1 is 2-CF3-5-pyrimidinyl, R2 is Me and R4 is H.
663B Q1 is 2-CF3-5-pyrimidinyl, R2 is Cl and R4 is H.
664B Q1 is 2-CF3-5-pyrimidinyl, R2 is Br and R4 is H.
665B Q1 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is Me.
666B Q1 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is CFH2.
667B Q1 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is Me.
668B Q1 is 5-Cl-2-pyrimidinyl, R2 is I and R4 is Me.
669B Q1 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is Me.
670B Q1 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is Cl.
671B Q1 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is Br.
672B Q1 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is I.
673B Q1 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is Br.
674B Q1 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is Cl.
675B Q1 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is Br.
676B Q1 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is Cl.
677B Q1 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is H.
678B Q1 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is H.
679B Q1 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is H.
680B Q1 is 5-Me-2-pyrimidinyl, R2 is Cl and R4 is Me.
681B Q1 is 5-Me-2-pyrimidinyl, R2 is Cl and R4 is CFH2.
682B Q1 is 5-Me-2-pyrimidinyl, R2 is Br and R4 is Me.
683B Q1 is 5-Me-2-pyrimidinyl, R2 is I and R4 is Me.
684B Q1 is 5-Me-2-pyrimidinyl, R2 is Me and R4 is Me.
685B Q1 is 5-Me-2-pyrimidinyl, R2 is Me and R4 is Cl.
686B Q1 is 5-Me-2-pyrimidinyl, R2 is Me and R4 is Br.
687B Q1 is 5-Me-2-pyrimidinyl, R2 is Me and R4 is I.
688B Q1 is 5-Me-2-pyrimidinyl, R2 is Br and R4 is Br. Table Row Heading
689B Q1 is 5-Me-2-pyrimidinyl, R2 is , Br and R4 is Cl.
690B Q1 is 5-Me-2-pyrimidinyl, R2 is , Cl and R4 is Br.
691B Q1 is 5-Me-2-pyrimidinyl, R2 is , Cl and R4 is Cl.
692B Q1 is 5-Me-2-pyrimidinyl, R2 is , Me and R4 is H.
693B Q1 is 5-Me-2-pyrimidinyl, R2 is , Cl and R4 is H.
694B Q1 is 5-Me-2-pyrimidinyl, R2 is , Br and R4 is H.
695B Q1 is 5-MeO-2-pyrimidinyl, R2 is Cl and R4 is Me.
696B Q1 is 5-MeO-2-pyrimidinyl, R2 is Cl and R4 is CFH2.
697B Q1 is 5-MeO-2-pyrimidinyl, R2 is Br and R4 is Me.
698B Q1 is 5-MeO-2-pyrimidinyl, R2 is I and R4 is Me.
699B Q1 is 5-MeO-2-pyrimidinyl, R2 is Me and R4 is Me.
700B Q1 is 5-MeO-2-pyrimidinyl, R2 is Me and R4 is Cl.
701B Q1 is 5-MeO-2-pyrimidinyl, R2 is Me and R4 is Br.
702B Q1 is 5-MeO-2-pyrimidinyl, R2 is Me and R4 is I.
703B Q1 is 5-MeO-2-pyrimidinyl, R2 is Br and R4 is Br.
704B Q1 is 5-MeO-2-pyrimidinyl, R2 is Br and R4 is Cl.
705B Q1 is 5-MeO-2-pyrimidinyl, R2 is Cl and R4 is Br.
706B Q1 is 5-MeO-2-pyrimidinyl, R2 is Cl and R4 is Cl.
707B Q1 is 5-MeO-2-pyrimidinyl, R2 is Me and R4 is H.
708B Q1 is 5-MeO-2-pyrimidinyl, R2 is Cl and R4 is H.
709B Q1 is 5-MeO-2-pyrimidinyl, R2 is Br and R4 is H.
710B Q1 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is Me.
711B Q1 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is CFH2.
712B Q1 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is Me.
713B Q1 is 5-Cl-2-pyrimidinyl, R2 is I and R4 is Me.
714B Q1 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is Me.
715B Q1 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is Cl.
716B Q1 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is Br.
717B Q1 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is I.
718B Q1 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is Br.
719B Q1 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is Cl.
720B Q1 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is Br.
721B Q1 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is Cl.
722B Q1 is 5-Cl-2-pyrimidinyl, R2 is Me and R4 is H.
723B Q1 is 5-Cl-2-pyrimidinyl, R2 is Cl and R4 is H.
724B Q1 is 5-Cl-2-pyrimidinyl, R2 is Br and R4 is H.
725B Q1 is 5-CF3-2-pyrimidinyl, R2 is Cl and R4 is Me. Table Row Heading
726B Q1 is 5-CF3-2-pyrimidinyl, R2 is Cl and R4 is CFH2.
727B Q1 is 5-CF3-2-pyrimidinyl, R2 is Br and R4 is Me.
728B Q1 is 5-CF3-2-pyrimidinyl, R2 is I and R4 is Me.
729B Q1 is 5-CF3-2-pyrimidinyl, R2 is Me and R4 is Me.
730B Q1 is 5-CF3-2-pyrimidinyl, R2 is Me and R4 is Cl.
731B Q1 is 5-CF3-2-pyrimidinyl, R2 is Me and R4 is Br.
732B Q1 is 5-CF3-2-pyrimidinyl, R2 is Me and R4 is I.
733B Q1 is 5-CF3-2-pyrimidinyl, R2 is Br and R4 is Br.
734B Q1 is 5-CF3-2-pyrimidinyl, R2 is Br and R4 is Cl.
735B Q1 is 5-CF3-2-pyrimidinyl, R2 is Cl and R4 is Br.
736B Q1 is 5-CF3-2-pyrimidinyl, R2 is Cl and R4 is Cl.
737B Q1 is 5-CF3-2-pyrimidinyl, R2 is Me and R4 is H.
738B Q1 is 5-CF3-2-pyrimidinyl, R2 is Cl and R4 is H.
739B Q1 is 5-CF3-2-pyrimidinyl, R2 is Br and R4 is H.
740B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Cl and R4 is Me.
741B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Cl and R4 is CFH2.
742B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Br and R4 is Me.
743B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is I and R4 is Me.
744B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Me and R4 is Me.
745B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Me and R4 is Cl.
746B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Me and R4 is Br.
747B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Me and R4 is I.
748B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Br and R4 is Br.
749B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Br and R4 is Cl.
750B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Cl and R4 is Br.
751B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Cl and R4 is Cl.
752B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Me and R4 is H.
753B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Cl and R4 is H.
754B Q1 is 4,6-di-MeO-l,3,4-triazin-2-yl, R2 is Br and R4 is H.
755B Q1 is 5-Me-2-thienyl, R2 is Cl and R4 is Me.
756B Q1 is 5-Me-2-thienyl, R2 is Cl and R4 is CFH2.
757B Q1 is 5-Me-2-thienyl, R2 is Br and R4 is Me.
758B Q1 is 5-Me-2-thienyl, R2 is I and R4 is Me.
759B Q1 is 5-Me-2-thienyl, R2 is Me and R4 is Me.
760B Q1 is 5-Me-2-thienyl, R2 is Me and R4 is Cl.
761B Q1 is 5-Me-2-thienyl, R2 is Me and R4 is Br.
762B Q1 is 5-Me-2-thienyl, R2 is Me and R4 is I. Table Row Heading
763B Q1 is 5-Me-2-thienyl, R2 is Br and R4 is Br.
764B Q1 is 5-Me-2-thienyl, R2 is Br and R4 is Cl.
765B Q1 is 5-Me-2-thienyl, R2 is Cl and R4 is Br.
766B Q1 is 5-Me-2-thienyl, R2 is Cl and R4 is Cl.
767B Q1 is 5-Me-2-thienyl, R2 is Me and R4 is H.
768B Q1 is 5-Me-2-thienyl, R2 is Cl and R4 is H.
769B Q1 is 5-Me-2-thienyl, R2 is Br and R4 is H.
770B Q1 is 5-Cl-2-thienyl, R2 is Cl and R4 is Me.
771B Q1 is 5-Cl-2-thienyl, R2 is Cl and R4 is CFH2.
772B Q1 is 5-Cl-2-thienyl, R2 is Br and R4 is Me.
773B Q1 is 5-Cl-2-thienyl, R2 is I and R4 is Me.
774B Q1 is 5-Cl-2-thienyl, R2 is Me and R4 is Me.
775B Q1 is 5-Cl-2-thienyl, R2 is Me and R4 is Cl.
776B Q1 is 5-Cl-2-thienyl, R2 is Me and R4 is Br.
777B Q1 is 5-Cl-2-thienyl, R2 is Me and R4 is I.
778B Q1 is 5-Cl-2-thienyl, R2 is Br and R4 is Br.
779B Q1 is 5-Cl-2-thienyl, R2 is Br and R4 is Cl.
780B Q1 is 5-Cl-2-thienyl, R2 is Cl and R4 is Br.
781B Q1 is 5-Cl-2-thienyl, R2 is Cl and R4 is Cl.
782B Q1 is 5-Cl-2-thienyl, R2 is Me and R4 is H.
783B Q1 is 5-Cl-2-thienyl, R2 is Cl and R4 is H.
784B Q1 is 5-Cl-2-thienyl, R2 is Br and R4 is H.
785B Q1 is 5-F-2-thienyl, R2 is Cl and R4 is Me.
786B Q1 is 5-F-2-thienyl, R2 is Cl and R4 is CFH2.
787B Q1 is 5-F-2-thienyl, R2 is Br and R4 is Me.
788B Q1 is 5-F-2-thienyl, R2 is I and R4 is Me.
789B Q1 is 5-F-2-thienyl, R2 is Me and R4 is Me.
790B Q1 is 5-F-2-thienyl, R2 is Me and R4 is Cl.
791B Q1 is 5-F-2-thienyl, R2 is Me and R4 is Br.
792B Q1 is 5-F-2-thienyl, R2 is Me and R4 is I.
793B Q1 is 5-F-2-thienyl, R2 is Br and R4 is Br.
794B Q1 is 5-F-2-thienyl, R2 is Br and R4 is Cl.
795B Q1 is 5-F-2-thienyl, R2 is Cl and R4 is Br.
796B Q1 is 5-F-2-thienyl, R2 is Cl and R4 is Cl.
797B Q1 is 5-F-2-thienyl, R2 is Me and R4 is H.
798B Q1 is 5-F-2-thienyl, R2 is Cl and R4 is H.
799B Q1 is 5-F-2-thienyl, R2 is Br and R4 is H. Table Row Heading
800B Q1 is 5-Me-3-thienyl, R2 is Cl and R4 is Me.
801B Q1 is 5-Me-3-thienyl, R2 is Cl and R4 is CFH2.
802B Q1 is 5-Me-3-thienyl, R2 is Br and R4 is Me.
803B Q1 is 5-Me-3-thienyl, R2 is I and R4 is Me.
804B Q1 is 5-Me-3-thienyl, R2 is Me and R4 is Me.
805B Q1 is 5-Me-3-thienyl, R2 is Me and R4 is Cl.
806B Q1 is 5-Me-3-thienyl, R2 is Me and R4 is Br.
807B Q1 is 5-Me-3-thienyl, R2 is Me and R4 is I.
808B Q1 is 5-Me-3-thienyl, R2 is Br and R4 is Br.
809B Q1 is 5-Me-3-thienyl, R2 is Br and R4 is Cl.
810B Q1 is 5-Me-3-thienyl, R2 is Cl and R4 is Br.
811B Q1 is 5-Me-3-thienyl, R2 is Cl and R4 is Cl.
812B Q1 is 5-Me-3-thienyl, R2 is Me and R4 is H.
813B Q1 is 5-Me-3-thienyl, R2 is Cl and R4 is H.
814B Q1 is 5-Me-3-thienyl, R2 is Br and R4 is H.
815B Q1 is 5-Cl-3-thienyl, R2 is Cl and R4 is Me.
816B Q1 is 5-Cl-3-thienyl, R2 is Cl and R4 is CFH2.
817B Q1 is 5-Cl-3-thienyl, R2 is Br and R4 is Me.
818B Q1 is 5-Cl-3-thienyl, R2 is I and R4 is Me.
819B Q1 is 5-Cl-3-thienyl, R2 is Me and R4 is Me.
820B Q1 is 5-Cl-3-thienyl, R2 is Me and R4 is Cl.
821B Q1 is 5-Cl-3-thienyl, R2 is Me and R4 is Br.
822B Q1 is 5-Cl-3-thienyl, R2 is Me and R4 is I.
823B Q1 is 5-Cl-3-thienyl, R2 is Br and R4 is Br.
824B Q1 is 5-Cl-3-thienyl, R2 is Br and R4 is Cl.
825B Q1 is 5-Cl-3-thienyl, R2 is Cl and R4 is Br.
826B Q1 is 5-Cl-3-thienyl, R2 is Cl and R4 is Cl.
827B Q1 is 5-Cl-3-thienyl, R2 is Me and R4 is H.
828B Q1 is 5-Cl-3-thienyl, R2 is Cl and R4 is H.
829B Q1 is 5-Cl-3-thienyl, R2 is Br and R4 is H.
830B Q1 is 5-F-3-thienyl, R2 is Cl and R4 is Me.
831B Q1 is 5-F-3-thienyl, R2 is Cl and R4 is CFH2.
832B Q1 is 5-F-3-thienyl, R2 is Br and R4 is Me.
833B Q1 is 5-F-3-thienyl, R2 is I and R4 is Me.
834B Q1 is 5-F-3-thienyl, R2 is Me and R4 is Me.
835B Q1 is 5-F-3-thienyl, R2 is Me and R4 is Cl.
836B Q1 is 5-F-3-thienyl, R2 is Me and R4 is Br. Table Row Heading
837B Q1 is 5-F-3-thienyl, R2 is Mt ; and R4 is I.
838B Q1 is 5-F-3-thienyl, R2 is Br and R4 is Br.
839B Q1 is 5-F-3-thienyl, R2 is Br and R4 is Cl.
840B Q1 is 5-F-3-thienyl, R2 is Cl and R4 is Br.
841B Q1 is 5-F-3-thienyl, R2 is Cl and R4 is Cl.
842B Q1 is 5-F-3-thienyl, R2 is Mt ; and R4 is H.
843B Q1 is 5-F-3-thienyl, R2 is Cl and R4 is H.
844B Q1 is 5-F-3-thienyl, R2 is Br and R4 is H.
845B Q1 is 1 -Me- li/-pyrazol-3 -yl, R2 is Cl and R4 is Me.
846B Q1 is 1 -Me- li/-pyrazol-3 -yl, R2 is Cl and R4 is CFH2.
847B Q1 is 1 -Me- li/-pyrazol-3 -yl, R2 is Br and R4 is Me.
848B Q1 is 1 -Me- li/-pyrazol-3 -yl, R2 is I and R4 is Me.
849B Q1 is 1 -Me- li/-pyrazol-3 -yl, R2 is Me and R4 is Me.
850B Q1 is 1 -Me- li/-pyrazol-3 -yl, R2 is Me and R4 is Cl.
851B Q1 is 1 -Me- l//-pyrazol-3 -yl, R2 is Me and R4 is Br.
852B Q1 is 1 -Me- l//-pyrazol-3 -yl, R2 is Me and R4 is I.
853B Q1 is 1 -Me- l//-pyrazol-3 -yl, R2 is Br and R4 is Br.
854B Q1 is 1 -Me- l//-pyrazol-3 -yl, R2 is Br and R4 is Cl.
855B Q1 is 1 -Me- l//-pyrazol-3 -yl, R2 is Cl and R4 is Br.
856B Q1 is 1 -Me- l//-pyrazol-3 -yl, R2 is Cl and R4 is Cl.
857B Q1 is 1 -Me- l//-pyrazol-3 -yl, R2 is Me and R4 is H.
858B Q1 is 1 -Me- l//-pyrazol-3 -yl, R2 is Cl and R4 is H.
859B Q1 is 1 -Me- l//-pyrazol-3 -yl, R2 is Br and R4 is H.
860B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Cl and R4 is Me.
861B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Cl and R4 is CFH2.
862B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Br and R4 is Me.
863B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is I and R4 is Me.
864B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Me and R4 is Me.
865B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Me and R4 is Cl.
866B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Me and R4 is Br.
867B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Me and R4 is I.
868B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Br and R4 is Br.
869B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Br and R4 is Cl.
870B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Cl and R4 is Br.
871B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Cl and R4 is Cl.
872B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Me and R4 is H.
873B Q1 is 1 -Me- l//-pyrazol-4-yl, R2 is Cl and R4 is H. Table Row Heading
874B Q1 is l-Me-l//-pyrazol-4-yl, R2 is Br and R4 is H.
875B Q1 is 2-Me-5-thiazolyl, R2 is Cl and R4 is Me.
876B Q1 is 2-Me-5-thiazolyl, R2 is Cl and R4 is CFH2.
877B Q1 is 2-Me-5-thiazolyl, R2 is Br and R4 is Me.
878B Q1 is 2-Me-5-thiazolyl, R2 is I and R4 is Me.
879B Q1 is 2-Me-5-thiazolyl, R2 is Me and R4 is Me.
880B Q1 is 2-Me-5-thiazolyl, R2 is Me and R4 is Cl.
881B Q1 is 2-Me-5-thiazolyl, R2 is Me and R4 is Br.
882B Q1 is 2-Me-5-thiazolyl, R2 is Me and R4 is I.
883B Q1 is 2-Me-5-thiazolyl, R2 is Br and R4 is Br.
884B Q1 is 2-Me-5-thiazolyl, R2 is Br and R4 is Cl.
885B Q1 is 2-Me-5-thiazolyl, R2 is Cl and R4 is Br.
886B Q1 is 2-Me-5-thiazolyl, R2 is Cl and R4 is Cl.
887B Q1 is 2-Me-5-thiazolyl, R2 is Me and R4 is H.
888B Q1 is 2-Me-5-thiazolyl, R2 is Cl and R4 is H.
889B Q1 is 2-Me-5-thiazolyl, R2 is Br and R4 is H.
890B Q1 is 2-Cl-5-thiazolyl, R2 is Cl and R4 is Me.
891B Q1 is 2-Cl-5-thiazolyl, R2 is Cl and R4 is CFH2.
892B Q1 is 2-Cl-5-thiazolyl, R2 is Br and R4 is Me.
893B Q1 is 2-Cl-5-thiazolyl, R2 is I and R4 is Me.
894B Q1 is 2-Cl-5-thiazolyl, R2 is Me and R4 is Me.
895B Q1 is 2-Cl-5-thiazolyl, R2 is Me and R4 is Cl.
896B Q1 is 2-Cl-5-thiazolyl, R2 is Me and R4 is Br.
897B Q1 is 2-Cl-5-thiazolyl, R2 is Me and R4 is I.
898B Q1 is 2-Cl-5-thiazolyl, R2 is Br and R4 is Br.
899B Q1 is 2-Cl-5-thiazolyl, R2 is Br and R4 is Cl.
900B Q1 is 2-Cl-5-thiazolyl, R2 is Cl and R4 is Br.
901B Q1 is 2-Cl-5-thiazolyl, R2 is Cl and R4 is Cl.
902B Q1 is 2-Cl-5-thiazolyl, R2 is Me and R4 is H.
903B Q1 is 2-Cl-5-thiazolyl, R2 is Cl and R4 is H.
904B Q1 is 2-Cl-5-thiazolyl, R2 is Br and R4 is H.
905B Q1 is 5-Me-3-isothiazolyl, R2 is Cl and R4 is Me.
906B Q1 is 5-Me-3-isothiazolyl, R2 is Cl and R4 is CFH2.
907B Q1 is 5-Me-3-isothiazolyl, R2 is Br and R4 is Me.
908B Q1 is 5-Me-3-isothiazolyl, R2 is I and R4 is Me.
909B Q1 is 5-Me-3-isothiazolyl, R2 is Me and R4 is Me.
910B Q1 is 5-Me-3-isothiazolyl, R2 is Me and R4 is Cl. Table Row Heading
911B Q1 is 5-Me-3-isothiazolyl, R2 is Me and R4 is Br.
912B Q1 is 5-Me-3-isothiazolyl, R2 is Me and R4 is I.
913B Q1 is 5-Me-3-isothiazolyl, R2 is Br and R4 is Br.
914B Q1 is 5-Me-3-isothiazolyl, R2 is Br and R4 is Cl.
915B Q1 is 5-Me-3-isothiazolyl, R2 is Cl and R4 is Br.
916B Q1 is 5-Me-3-isothiazolyl, R2 is Cl and R4 is Cl.
917B Q1 is 5-Me-3-isothiazolyl, R2 is Me and R4 is H.
918B Q1 is 5-Me-3-isothiazolyl, R2 is Cl and R4 is H.
919B Q1 is 5-Me-3-isothiazolyl, R2 is Br and R4 is H.
920B Q1 is 5-Cl-3-isothiazolyl, R2 is Cl and R4 is Me.
921B Q1 is 5-Cl-3-isothiazolyl, R2 is Cl and R4 is CFH2.
922B Q1 is 5-Cl-3-isothiazolyl, R2 is Br and R4 is Me.
923B Q1 is 5-Cl-3-isothiazolyl, R2 is I and R4 is Me.
924B Q1 is 5-Cl-3-isothiazolyl, R2 is Me and R4 is Me.
925B Q1 is 5-Cl-3-isothiazolyl, R2 is Me and R4 is Cl.
926B Q1 is 5-Cl-3-isothiazolyl, R2 is Me and R4 is Br.
927B Q1 is 5-Cl-3-isothiazolyl, R2 is Me and R4 is I.
928B Q1 is 5-Cl-3-isothiazolyl, R2 is Br and R4 is Br.
929B Q1 is 5-Cl-3-isothiazolyl, R2 is Br and R4 is Cl.
930B Q1 is 5-Cl-3-isothiazolyl, R2 is Cl and R4 is Br.
931B Q1 is 5-Cl-3-isothiazolyl, R2 is Cl and R4 is Cl.
932B Q1 is 5-Cl-3-isothiazolyl, R2 is Me and R4 is H.
933B Q1 is 5-Cl-3-isothiazolyl, R2 is Cl and R4 is H.
934B Q1 is 5-Cl-3-isothiazolyl, R2 is Br and R4 is H.
Table 3
Figure imgf000139_0001
R2 is Cl, R4 is Me and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
6-CF3-3-pyridinyl 5-Me-3-pyridinyl
2-Cl, 6-CF3-3-pyridinyl 5-F-3-pyridinyl
2-Cl, 6-MeO-3-pyridinyl 6-Me-3 -pyridinyl
2-Cl, 6-Me-3-pyridinyl 6-Cl-3-pyridinyl
Figure imgf000139_0002
R2 is Cl, R4 is Me and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
6-MeO-3 -pyridinyl 5-Cl-3-pyridinyl
6-Br-3 -pyridinyl 6-CF3 -3 -pyridinyl
2-CF3-5-pyridinyl 2-Cl-5-pyridinyl
6-Me-3 -pyridinyl 6-C1-3 -pyridinyl
2-MeO-5-pyridinyl
Figure imgf000140_0001
The present disclosure also includes Tables 1C through 62C, each of which is constructed the same as Table 3 above except that the row heading in Table 3 (i.e. "R2 is Cl, R4 is Me and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O") is replaced with the respective row heading shown below. Thus, for example, in Table 1C the row heading is "R2 is Cl, R4 is Cl and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O", and Q2 is as defined in Table 3 above. Tables 2C through 62C are constructed similarly.
Table Number Row Heading
1C R2 is Cl, R4 is Cl and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
2C R2 is Cl, R4 is Br and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
3C R2 is Br, R4 is Me and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
4C R2 is Br, R4 is Cl and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
5C R2 is Me, R4 is Me and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
6C R2 is Br, R4 is Br and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
7C R2 is Cl, R4 is Me and (R5a)m i 3 2,6-di-F, 4-Me2N(CH2)3O_
8C R2 is Cl, R4 is Cl and (R5a)m is 2,6-di-F, 4-Me2N(CH2)3O_
9C R2 is Cl, R4 is Br and (R5a)m is 2,6-di-F, 4-Me2N(CH2)3O_
1OC R2 is Br, R4 is Me and (R5a)m is 2,6-di-F, 4-Me2N(CH2)3O.
11c R2 is Br, R4 is Cl and (R5a)m is 2,6-di-F, 4-Me2N(CH2)3O_
12c R2 is Me, R4 is Me and (R5a)m is 2,6-di-F, 4-Me2N(CH2)3O_
13C R2 is Br, R4 is Br and (R5a)m is 2,6-di-F, 4-Me2N(CH2)3O_
14C R2 is Cl, R4 is Me, and (R5a)m 1 s 2,6-di-F, 4-MeO(CH2)3O.
15C R2 is Cl, R4 is Cl and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O.
16C R2 is Cl, R4 is Br and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O.
17C R2 is Br, R4 is Me and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O.
18C R2 is Br, R4 is Cl and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O.
19C R2 is Me, R4 is Me and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O.
2OC R2 is Br, R4 is Br and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O.
21C R2 is Cl, R4 is Me and (R5a)m i 3 2-C1-6-F, 4-MeNH(CH2)3O.
22C R2 is Cl, R4 is Cl and (R5a)m is 2-C1-6-F, 4-MeNH(CH2)3O.
23C R2 is Cl, R4 is Br and (R5a)m is 2-C1-6-F, 4-MeNH(CH2)3O. Table Number Row Heading
24C R2 is Br, R4 is Me and (R5a)m is 2-C1-6-F, 4-MeNH(CH2)3O.
25C R2 is Br, R4 is Cl and (R5a)m is 2-C1-6-F, 4-MeNH(CH2)3O.
26C R2 is Me, R4 is Me and (R5a)m is 2-C1-6-F, 4-MeNH(CH2)3O.
27C R2 is Br, R4 is Br and (R5a)m is 2-C1-6-F, 4-MeNH(CH2)3O.
28C R2 is Cl, R4 is Me and (R5a)m i 3 2,6-di-F, 3-MeNH(CH2)3O.
29C R2 is Cl, R4 is Cl and (R5a)m is 2,6-di-F, 3-MeNH(CH2)3O.
3OC R2 is Cl, R4 is Br and (R5a)m is 2,6-di-F, 3-MeNH(CH2)3O.
31C R2 is Br, R4 is Me and (R5a)m is 2,6-di-F, 3-MeNH(CH2)3θ.
32C R2 is Br, R4 is Cl and (R5a)m is 2,6-di-F, 3-MeNH(CH2)3O.
33C R2 is Me, R4 is Me and (R5a)m is 2,6-di-F, 3-MeNH(CH2)3O.
34C R2 is Br, R4 is Br and (R5a)m is 2,6-di-F, 3-MeNH(CH2)3O.
35C R2 is Cl, R4 is Me and (R5a)m i 3 2,6-di-F, 3-Me2N(CH2)3O_
36C R2 is Cl, R4 is Cl and (R5a)m is 2,6-di-F, 3-Me2N(CH2)3O_
37C R2 is Cl, R4 is Br and (R5a)m is 2,6-di-F, 3-Me2N(CH2)3O_
38C R2 is Br, R4 is Me and (R5a)m is 2,6-di-F, 3-Me2N(CH2)3O.
39C R2 is Br, R4 is Cl and (R5a)m is 2,6-di-F, 3-Me2N(CH2)3O_
4OC R2 is Me, R4 is Me and (R5a)m is 2,6-di-F, 3-Me2N(CH2)3O_
41C R2 is Br, R4 is Br and (R5a)m is 2,6-di-F, 3-Me2N(CH2)3O_
42C R2 is Cl, R4 is Me, and (R5a)m i s 2,6-di-F, 3-MeO(CH2)3O.
43C R2 is Cl, R4 is Cl and (R5a)m is 2,6-di-F, 3-MeO(CH2)3O.
44C R2 is Cl, R4 is Br and (R5a)m is 2,6-di-F, 3-MeO(CH2)3O.
45C R2 is Br, R4 is Me and (R5a)m is 2,6-di-F, 3-MeO(CH2)3O.
46C R2 is Br, R4 is Cl and (R5a)m is 2,6-di-F, 3-MeO(CH2)3O.
46C R2 is Me, R4 is Me and (R5a)m is 2,6-di-F, 3-MeO(CH2)3O.
48C R2 is Br, R4 is Br and (R5a)m is 2,6-di-F, 3-MeO(CH2)3O.
49C R2 is Cl, R4 is Me and (R5a)m i 3 2-C1-6-F, 3-MeNH(CH2)3O.
5OC R2 is Cl, R4 is Cl and (R5a)m is 2-C1-6-F, 3-MeNH(CH2)3O.
51C R2 is Cl, R4 is Br and (R5a)m is 2-C1-6-F, 3-MeNH(CH2)3O.
52C R2 is Br, R4 is Me and (R5a)m is 2-C1-6-F, 3-MeNH(CH2)3O.
53C R2 is Br, R4 is Cl and (R5a)m is 2-C1-6-F, 3-MeNH(CH2)3O.
54C R2 is Me, R4 is Me and (R5a)m is 6-C1-6-F, 3-MeNH(CH2)3O.
55C R2 is Br, R4 is Br and (R5a)m is 2-C1-6-F, 3-MeNH(CH2)3O.
56C R2 is Cl, R4 is Me and (R5a)m i 3 6-C1-2-F, 3-MeNH(CH2)3O.
57C R2 is Cl, R4 is Cl and (R5a)m is 6-C1-2-F, 3-MeNH(CH2)3O.
58C R2 is Cl, R4 is Br and (R5a)m is 6-C1-2-F, 3-MeNH(CH2)3O.
59C R2 is Br, R4 is Me and (R5a)m is 6-C1-2-F, 3-MeNH(CH2)3O.
6OC R2 is Br, R4 is Cl and (R5a)m is 6-C1-2-F, 3-MeNH(CH2)3O. Table Number Row Heading
61C R2 is Me, R4 is Me and (R5a)m is 6-C1-2-F, 3-MeNH(CH2)3O. 62C R2 is Br, R4 is Br and (R5a)m is 6-C1-2-F, 3-MeNH(CH2)3θ.
Table 4
Figure imgf000142_0001
R2 is Cl, R4 is Me and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O.
Figure imgf000142_0002
6-CF3-3-pyridinyl 5-Me-3-pyridinyl
2-Cl, 6-CF3 -3 -pyridinyl 5-F-3-pyridinyl
2-Cl, 6-MeO-3-pyridinyl 6-Me-3 -pyridinyl
2-Cl, 6-Me-3 -pyridinyl 6-C1-3 -pyridinyl
6-MeO-3 -pyridinyl 5-Cl-3-pyridinyl
6-Br-3 -pyridinyl 6-CF3 -3 -pyridinyl
2-CF3-5-pyridinyl 2 -Cl- 5 -pyridinyl
6-Me-3 -pyridinyl 6-C1-3 -pyridinyl
2-MeO-5-pyridinyl
Figure imgf000142_0003
The present disclosure also includes Tables ID through 62D, each of which is constructed the same as Table 4 above except that the row heading in Table 4 (i.e. "R2 is Cl, R4 is Me and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O") is replaced with the respective row heading shown below. Thus, for example, in Table ID the row heading is "R2 is Cl, R4 is Cl and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O", and Q1 is as defined in Table 4 above. Tables 2D through 62D are constructed similarly.
Table Number Row Heading
ID R2 is Cl, R4 is Cl and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O. 2D R2 is Cl, R4 is Br and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O. 3D R2 is Br, R4 is Me and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O. 4D R2 is Br, R4 is Cl and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O. 5D R2 is Me, R4 is Me and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O. 6D R2 is Br, R4 is Br and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O. 7D R2 is Cl, R4 is Me and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3O Table Number Row Heading
8D R2 is Cl, R4 is Cl and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3O_
9D R2 is Cl, R4 is Br and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3O_
1OD R2 is Br, R4 is Me and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3O.
HD R2 is Br, R4 is Cl and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3O_
12D R2 is Me , R4 is Me and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3O_
13D R2 is Br, R4 is Br and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3O_
14D R2 is Cl, R4 is Me, and (R5b)n s 2,6-di-F, 4-MeO(CH2)3O.
15D R2 is Cl, R4 is Cl and (R5b)n is 2,6-di-F, 4-MeO(CH2)3O.
16D R2 is Cl, R4 is Br and (R5b)n is 2,6-di-F, 4-MeO(CH2)3O.
17D R2 is Br, R4 is Me and (R5b)n is 2,6-di-F, 4-MeO(CH2)3O.
18D R2 is Br, R4 is Cl and (R5b)n is 2,6-di-F, 4-MeO(CH2)3O.
19D R2 is Me , R4 is Me and (R5b)n is 2,6-di-F, 4-MeO(CH2)3O.
2OD R2 is Br, R4 is Br and (R5b)n is 2,6-di-F, 4-MeO(CH2)3O.
21D R2 is Cl, R4 is Me and (R5b)n i 5 2-C1-6-F, 4-MeNH(CH2)3O.
22D R2 is Cl, R4 is Cl and (R5b)n is 2-C1-6-F, 4-MeNH(CH2)3O.
23D R2 is Cl, R4 is Br and (R5b)n is 2-C1-6-F, 4-MeNH(CH2)3O.
24D R2 is Br, R4 is Me and (R5b)n is 2-C1-6-F, 4-MeNH(CH2)3θ.
25D R2 is Br, R4 is Cl and (R5b)n is 2-C1-6-F, 4-MeNH(CH2)3O.
26D R2 is Me , R4 is Me and (R5b)n is 2-C1-6-F, 4-MeNH(CH2)3O.
27D R2 is Br, R4 is Br and (R5b)n is 2-C1-6-F, 4-MeNH(CH2)3O.
28D R2 is Cl, R4 is Me and (R5b)n i 5 2,6-di-F, 3-MeNH(CH2)3O.
29D R2 is Cl, R4 is Cl and (R5b)n is 2,6-di-F, 3-MeNH(CH2)3O.
3OD R2 is Cl, R4 is Br and (R5b)n is 2,6-di-F, 3-MeNH(CH2)3O.
31D R2 is Br, R4 is Me and (R5b)n is 2,6-di-F, 3-MeNH(CH2)3O.
32D R2 is Br, R4 is Cl and (R5b)n is 2,6-di-F, 3-MeNH(CH2)3O.
33D R2 is Me , R4 is Me and (R5b)n is 2,6-di-F, 3-MeNH(CH2)3O.
34D R2 is Br, R4 is Br and (R5b)n is 2,6-di-F, 3-MeNH(CH2)3O.
35D R2 is Cl, R4 is Me and (R5b)n i 5 2,6-di-F, 3-Me2N(CH2)3O_
36D R2 is Cl, R4 is Cl and (R5b)n is 2,6-di-F, 3-Me2N(CH2)3O_
37D R2 is Cl, R4 is Br and (R5b)n is 2,6-di-F, 3-Me2N(CH2)3O_
38D R2 is Br, R4 is Me and (R5b)n is 2,6-di-F, 3-Me2N(CH2)3O.
39D R2 is Br, R4 is Cl and (R5b)n is 2,6-di-F, 3-Me2N(CH2)3O_
4OD R2 is Me , R4 is Me and (R5b)n is 2,6-di-F, 3-Me2N(CH2)3O_
41D R2 is Br, R4 is Br and (R5b)n is 2,6-di-F, 3-Me2N(CH2)3O_
42D R2 is Cl, R4 is Me, and (R5b)n i s 2,6-di-F, 3-MeO(CH2)3O.
43D R2 is Cl, R4 is Cl and (R5b)n is 2,6-di-F, 3-MeO(CH2)3O.
44D R2 is Cl, R4 is Br and (R5b)n is 2,6-di-F, 3-MeO(CH2)3O. Table Number Row Heading
45D R2 is Br, R4 is Me and (R5b)n is 2,6-di-F, 3-MeO(CH2)3O.
46D R2 is Br, R4 is Cl and (R5b)n is 2,6-di-F, 3-MeO(CH2)3O.
46D R2 is Me, R4 is Me and (R5b)n is 2,6-di-F, 3-MeO(CH2)3O.
48D R2 is Br, R4 is Br and (R5b)n is 2,6-di-F, 3-MeO(CH2)3O.
49D R2 is Cl, R4 is Me and (R5b)n i 3 2-C1-6-F, 3-MeNH(CH2)3O.
5OD R2 is Cl, R4 is Cl and (R5b)n is 2-C1-6-F, 3-MeNH(CH2)3O.
51D R2 is Cl, R4 is Br and (R5b)n is 2-C1-6-F, 3-MeNH(CH2)3O.
52D R2 is Br, R4 is Me and (R5b)n is 2-C1-6-F, 3-MeNH(CH2)3θ.
53D R2 is Br, R4 is Cl and (R5b)n is 2-C1-6-F, 3-MeNH(CH2)3O.
54D R2 is Me, R4 is Me and (R5b)n is 6-C1-6-F, 3-MeNH(CH2)3O.
55D R2 is Br, R4 is Br and (R5b)n is 2-C1-6-F, 3-MeNH(CH2)3O.
56D R2 is Cl, R4 is Me and (R5b)n i 3 6-C1-2-F, 3-MeNH(CH2)3O.
57D R2 is Cl, R4 is Cl and (R5b)n is 6-C1-2-F, 3-MeNH(CH2)3O.
58D R2 is Cl, R4 is Br and (R5b)n is 6-C1-2-F, 3-MeNH(CH2)3O.
59D R2 is Br, R4 is Me and (R5b)n is 6-C1-2-F, 3-MeNH(CH2)3O.
6OD R2 is Br, R4 is Cl and (R5b)n is 6-C1-2-F, 3-MeNH(CH2)3O.
61D R2 is Me, R4 is Me and (R5b)n is 6-C1-2-F, 3-MeNH(CH2)3O.
62D R2 is Br, R4 is Br and (R5b)n is 6-C1-2-F, 3-MeNH(CH2)3O.
Figure imgf000144_0001
Q3 is 4-Cl-Ph, R3 is Cl and R1 is Me.
Figure imgf000144_0003
Figure imgf000144_0002
Q3 is 4-Cl-Ph, R3 is Cl and R1 is Me.
(R5a} (R5a} (R5a} (R5a}
'm 'm 'm 'm (R5a> m
2,6-di-F, 4-EtO 2-Cl, 6-F, 4-MeO 2,6-di-F, 4-CF2HO 2,6-di-F, 4-NO2 2-Cl, 3,6-di-F 2-Cl, 6-F, 5-MeO 2,6-di-F, 3-CF2HO 2,6-di-F, 3-EtO
The present disclosure also includes Tables IE through 387E, each of which is constructed the same as Table 5 above except that the row heading in Table 5 (i.e. "Q3 is 4-Cl-Ph, R3 is Cl and R1 is Me") is replaced with the respective row heading shown below. Thus, for example, in Table IE the row heading is "Q3 is 4-Cl-Ph, R3 is Cl and R1 is CFH2", and (R5a)m is as defined in Table 5 above. Tables 2E through 387E are constructed similarly.
Table Number Row Heading
IE Q3 is 4-Cl-Ph, R3 is Cl and R1 is CFH2. 2E Q3 is 4-Cl-Ph, R3 is Br and R1 is Me. 3E Q3 is 4-Cl-Ph, R3 is I and R1 is Me. 4E Q3 is 4-Cl-Ph, R3 is Me and R1 is Me. 5E Q3 is 4-Cl-Ph, R3 is MeO and R1 is Me. 6E Q3 is 4-Cl-Ph, R3 is MeS and R1 is Me. 7E Q3 is 4-Cl-Ph, R3 is Et and R1 is Me. 8E Q3 is 4-Cl-Ph, R3 is Me and R1 is Et. 9E Q3 is 4-Cl-Ph, R3 is Cl and R1 is Et. 1OE Q3 is 3-Cl-Ph, R3 is Cl and R1 is Me.
HE Q3 is 3-Cl-Ph, R3 is Cl and R1 is CFH2.
12E Q3 is 3 -Cl-Ph, R3 is Br and R1 is Me. 13E Q3 is 3 -Cl-Ph, R3 is I and R1 is Me. 14E Q3 is 3-Cl-Ph, R3 is Me and R1 is Me. 15E Q3 is 3-Cl-Ph, R3 is MeO and R1 is Me. 16E Q3 is 3-Cl-Ph, R3 is MeS and R1 is Me. 17E Q3 is 3-Cl-Ph, R3 is Et and R1 is Me. 18E Q3 is 3-Cl-Ph, R3 is Me and R1 is Et. 19E Q3 is 3-Cl-Ph, R3 is Cl and R1 is Et. 2OE Q3 is 4-F-Ph, R3 is Cl and R1 is Me. 21E Q3 is 4-F-Ph, R3 is Cl and R1 is CFH2. 22E Q3 is 4-F-Ph, R3 is Br and R1 is Me. 23E Q3 is 4-F-Ph, R3 is I and R1 is Me. 24E Q3 is 4-F-Ph, R3 is Me and R1 is Me. 25E Q3 is 4-F-Ph, R3 is MeO and R1 is Me. 26E Q3 is 4-F-Ph, R3 is MeS and R1 is Me. Table Number Row Heading
27E Q3 is 4-F-Ph, R3 is Et and R1 is Me.
28E Q3 is 4-F-Ph, R3 is Me and R1 is Et.
29E Q3 is 4-F-Ph, R3 is Cl and R1 is Et.
3OE Q3 is 3-F-Ph, R3 is Cl and R1 is Me.
31E Q3 is 3-F-Ph, R3 is Cl and R1 is CFH2.
32E Q3 is 3-F-Ph, R3 is Br and R1 is Me.
33E Q3 is 3-F-Ph, R3 is I and R1 is Me.
34E Q3 is 3-F-Ph, R3 is Me and R1 is Me.
35E Q3 is 3-F-Ph, R3 is MeO and R1 is Me.
36E Q3 is 3-F-Ph, R3 is MeS and R1 is Me.
37E Q3 is 3-F-Ph, R3 is Et and R1 is Me.
38E Q3 is 3-F-Ph, R3 is Me and R1 is Et.
39E Q3 is 3-F-Ph, R3 is Cl and R1 is Et.
4OE Q3 is 3-CF2HO-Ph, R3 is Cl and R1 is Me.
41E Q3 is 3-CF2HO-Ph, R3 is Cl and R1 is CFH2.
42E Q3 is 3-CF2HO-Ph, R3 is Br and R1 is Me.
43E Q3 is 3-CF2HO-Ph, R3 is I and R1 is Me.
44E Q3 is 3-CF2HO-Ph, R3 is Me and R1 is Me.
45E Q3 is 3-CF2HO-Ph, R3 is MeO and R1 is Me.
46E Q3 is 3-CF2HO-Ph, R3 is MeS and R1 is Me.
47E Q3 is 3-CF2HO-Ph, R3 is Et and R1 is Me.
48E Q3 is 3-CF2HO-Ph, R3 is Me and R1 is Et.
49E Q3 is 3-CF2HO-Ph, R3 is Cl and R1 is Et.
5OE Q3 is 4-Me-Ph, R3 is Cl and R1 is Me.
51E Q3 is 4-Me-Ph, R3 is Cl and R1 is CFH2.
52E Q3 is 4-Me-Ph, R3 is Br and R1 is Me.
53E Q3 is 4-Me-Ph, R3 is I and R1 is Me.
54E Q3 is 4-Me-Ph, R3 is Me and R1 is Me.
55E Q3 is 4-Me-Ph, R3 is MeO and R1 is Me.
56E Q3 is 4-Me-Ph, R3 is MeS and R1 is Me.
57E Q3 is 4-Me-Ph, R3 is Et and R1 is Me.
58E Q3 is 4-Me-Ph, R3 is Me and R1 is Et.
59E Q3 is 4-Me-Ph, R3 is Cl and R1 is Et.
6OE Q3 is 3-Me-Ph, R3 is Cl and R1 is Me.
61E Q3 is 3-Me-Ph, R3 is Cl and R1 is CFH2.
62E Q3 is 3-Me-Ph, R3 is Br and R1 is Me.
63E Q3 is 3-Me-Ph, R3 is I and R1 is Me. Table Number Row Heading
64E Q3 is 3-Me-Ph, R3 is Me and R1 is Me.
65E Q3 is 3-Me-Ph, R3 is MeO and R1 is Me.
66E Q3 is 3-Me-Ph, R3 is MeS and R1 is Me.
67E Q3 is 3-Me-Ph, R3 is Et and R1 is Me.
68E Q3 is 3-Me-Ph, R3 is Me and R1 is Et.
69E Q3 is 3-Me-Ph, R3 is Cl and R1 is Et.
7OE Q3 is 4-Et-Ph, R3 is Cl and R1 is Me.
71E Q3 is 4-Et-Ph, R3 is Cl and R1 is CFH2.
72E Q3 is 4-Et-Ph, R3 is Br and R1 is Me.
73E Q3 is 4-Et-Ph, R3 is I and R1 is Me.
74E Q3 is 4-Et-Ph, R3 is Me and R1 is Me.
75E Q3 is 4-Et-Ph, R3 is MeO and R1 is Me.
76E Q3 is 4-Et-Ph, R3 is MeS and R1 is Me.
77E Q3 is 4-Et-Ph, R3 is Et and R1 is Me.
78E Q3 is 4-Et-Ph, R3 is Me and R1 is Et.
79E Q3 is 4-Et-Ph, R3 is Cl and R1 is Et.
8OE Q3 is 4-Cl, 3-F-Ph, R3 is Cl and R1 is Me.
81E Q3 is 4-Cl, 3-F-Ph, R3 is Cl and R1 is CFH2.
82E Q3 is 4-Cl, 3-F-Ph, R3 is Br and R1 is Me.
83E Q3 is 4-Cl, 3-F-Ph, R3 is I and R1 is Me.
84E Q3 is 4-Cl, 3-F-Ph, R3 is Me and R1 is Me.
85E Q3 is 4-Cl, 3-F-Ph, R3 is MeO and R1 is Me.
86E Q3 is 4-Cl, 3-F-Ph, R3 is MeS and R1 is Me.
87E Q3 is 4-Cl, 3-F-Ph, R3 is Et and R1 is Me.
88E Q3 is 4-Cl, 3-F-Ph, R3 is Me and R1 is Et.
89E Q3 is 4-Cl, 3-F-Ph, R3 is Cl and R1 is Et.
9OE Q3 is 2-Cl, 4-F-Ph, R3 is Cl and R1 is Me.
91E Q3 is 2-Cl, 4-F-Ph, R3 is Cl and R1 is CFH2.
92E Q3 is 2-Cl, 4-F-Ph, R3 is Br and R1 is Me.
93E Q3 is 2-Cl, 4-F-Ph, R3 is I and R1 is Me.
94E Q3 is 2-Cl, 4-F-Ph, R3 is Me and R1 is Me.
95E Q3 is 2-Cl, 4-F-Ph, R3 is MeO and R1 is Me.
96E Q3 is 2-Cl, 4-F-Ph, R3 is MeS and R1 is Me.
97E Q3 is 2-Cl, 4-F-Ph, R3 is Et and R1 is Me.
98E Q3 is 2-Cl, 4-F-Ph, R3 is Me and R1 is Et.
99E Q3 is 2-Cl, 4-F-Ph, R3 is Cl and R1 is Et.
IOOE Q3 is 4-F, 3-Me-Ph, R3 is Cl and R1 is Me. Table Number Row Heading
101E Q3 is 4-F, 3-Me-Ph, R3 is Cl and R1 is CFH2.
102E Q3 is 4-F, 3-Me-Ph, R3 is Br and R1 is Me.
103E Q3 is 4-F, 3-Me-Ph, R3 is I and R1 is Me.
104E Q3 is 4-F, 3-Me-Ph, R3 is Me and R1 is Me.
105E Q3 is 4-F, 3-Me-Ph, R3 is MeO and R1 is Me.
106E Q3 is 4-F, 3-Me-Ph, R3 is MeS and R1 is Me.
107E Q3 is 4-F, 3-Me-Ph, R3 is Et and R1 is Me.
108E Q3 is 4-F, 3-Me-Ph, R3 is Me and R1 is Et.
109E Q3 is 4-F, 3-Me-Ph, R3 is Cl and R1 is Et.
HOE Q3 is 3,4-di-F-Ph, R3 is Cl and R1 is Me.
H IE Q3 is 3,4-di-F-Ph, R3 is Cl and R1 is CFH2.
112E Q3 is 3,4-di-F-Ph, R3 is Br and R1 is Me.
113E Q3 is 3,4-di-F-Ph, R3 is I and R1 is Me.
114E Q3 is 3,4-di-F-Ph, R3 is Me and R1 is Me.
115E Q3 is 3,4-di-F-Ph, R3 is MeO and R1 is Me.
116E Q3 is 3,4-di-F-Ph, R3 is MeS and R1 is Me.
117E Q3 is 3,4-di-F-Ph, R3 is Et and R1 is Me.
118E Q3 is 3,4-di-F-Ph, R3 is Me and R1 is Et.
119E Q3 is 3,4-di-F-Ph, R3 is Cl and R1 is Et.
120E Q3 is 3,4-di-Cl-Ph, R3 is Cl and R1 is Me.
121E Q3 is 3,4-di-Cl-Ph, R3 is Cl and R1 is CFH2.
122E Q3 is 3,4-di-Cl-Ph, R3 is Br and R1 is Me.
123E Q3 is 3,4-di-Cl-Ph, R3 is I and R1 is Me.
124E Q3 is 3,4-di-Cl-Ph, R3 is Me and R1 is Me.
125E Q3 is 3,4-di-Cl-Ph, R3 is MeO and R1 is Me.
126E Q3 is 3,4-di-Cl-Ph, R3 is MeS and R1 is Me.
127E Q3 is 3,4-di-Cl-Ph, R3 is Et and R1 is Me.
128E Q3 is 3,4-di-Cl-Ph, R3 is Me and R1 is Et.
129E Q3 is 3,4-di-Cl-Ph, R3 is Cl and R1 is Et.
13OE Q3 is 3,5-di-MeO-Ph, R3 is Cl and R1 is Me.
131E Q3 is 3,5-di-MeO-Ph, R3 is Cl and R1 is CFH2.
132E Q3 is 3,5-di-MeO-Ph, R3 is Br and R1 is Me.
133E Q3 is 3,5-di-MeO-Ph, R3 is I and R1 is Me.
134E Q3 is 3,5-di-MeO-Ph, R3 is Me and R1 is Me.
135E Q3 is 3,5-di-MeO-Ph, R3 is MeO and R1 is Me.
136E Q3 is 3,5-di-MeO-Ph, R3 is MeS and R1 is Me.
137E Q3 is 3,5-di-MeO-Ph, R3 is Et and R1 is Me. Table Number Row Heading
138E Q3 is 3,5-di-MeO-Ph, R3 is Mt ; and RI is Et.
139E Q3 is 3,5-di-MeO-Ph, R3 is Cl and R1 is Et.
140E Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Cl and RI is Me.
141E Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Cl and RI is CFH2.
142E Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Br and RI is Me.
143E Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is I and RI is Me.
144E Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Me and RI is Me.
145E Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is MeO and RI is Me.
146E Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is MeS and RI is Me.
147E Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Et and RI is Me.
148E Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Me and RI is Et.
149E Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Cl and RI is Et.
150E Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Cl and RI is Me.
151E Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Cl and RI is CFH2.
152E Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Br and RI is Me.
153E Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is I and RI is Me.
154E Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Me and RI is Me.
155E Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is MeO and RI is Me.
156E Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is MeS and RI is Me.
157E Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Et and RI is Me.
158E Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Me and RI is Et.
159E Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Cl and RI is Et.
160E Q3 is 4-Cl-Bn, R3 is Cl and Rl is Me.
161E Q3 is 4-Cl-Bn, R3 is Cl and Rl is CFH2.
162E Q3 is 4-Cl-Bn, R3 is Br and Rl is Me.
163E Q3 is 4-Cl-Bn, R3 is I and R1 is Me.
164E Q3 is 4-Cl-Bn, R3 is Me and R1 is Me.
165E Q3 is 4-Cl-Bn, R3 is MeO and Rl is Me.
166E Q3 is 4-Cl-Bn, R3 is MeS and Rl is Me.
167E Q3 is 4-Cl-Bn, R3 is Et and Rl is Me.
168E Q3 is 4-Cl-Bn, R3 is Me and R1 is Et.
169E Q3 is 4-Cl-Bn, R3 is Cl and Rl is Et.
170E Q3 is 4-F-Bn, R3 is Cl and 1 is I VIe.
171E Q3 is 4-F-Bn, R3 is Cl and 1 *i is CFH2.
172E Q3 is 4-F-Bn, R3 is Br and ] Rl is ! VIe.
173E Q3 is 4-F-Bn, R3 is I and R l is Me.
174E Q3 is 4-F-Bn, R3 is Me and Rl is Me. Table Number Row Heading
175E Q3 is 4-F-Bn, R3 is MeO and R1 is Me.
176E Q3 is 4-F-Bn, R3 is MeS and R1 is Me.
177E Q3 is 4-F-Bn, R3 is Et and R1 is Me.
178E Q3 is 4-F-Bn, R3 is Me and R1 is Et.
179E Q3 is 4-F-Bn, R3 is Cl and R1 is Et.
180E Q3 is 6-Cl-3-pyridinyl, R3 is Cl and R1 is Me.
181E Q3 is 6-Cl-3-pyridinyl, R3 is Cl and R1 is CFH2.
182E Q3 is 6-Cl-3-pyridinyl, R3 is Br and RMs Me.
183E Q3 is 6-Cl-3-pyridinyl, R3 is I and RMs Me.
184E Q3 is 6-Cl-3-pyridinyl, R3 is Me and R^ is Me.
185E Q3 is 6-Cl-3-pyridinyl, R3 is MeO and RMs Me.
186E Q3 is 6-Cl-3-pyridinyl, R3 is MeS and RMs Me.
187E Q3 is 6-Cl-3-pyridinyl, RJ is Et and RMs Me.
188E Q3 is 6-Cl-3-pyridinyl, R3 is Me and RMs Et.
189E Q3 is 6-Cl-3-pyridinyl, R3 is Cl and R1 is Et.
190E Q3 is 6-Me-3-pyridinyl, R3 is Cl and R^ is Me.
191E Q3 is 6-Me-3-pyridinyl, R3 is Cl and R1 is CFH2.
192E Q3 is 6-Me-3-pyridinyl, R3 is Br and R^ is Me.
193E Q3 is 6-Me-3-pyridinyl, R3 is I and R^ is Me.
194E Q3 is 6-Me-3-pyridinyl, R3 is Me and R^ is Me.
195E Q3 is 6-Me-3-pyridinyl, R3 is MeO and R^ is Me.
196E Q3 is 6-Me-3-pyridinyl, R3 is MeS and R^ is Me.
197E Q3 is 6-Me-3-pyridinyl, R3 is Et and R^ is Me.
198E Q3 is 6-Me-3-pyridinyl, R3 is Me and R^ is Et.
199E Q3 is 6-Me-3-pyridinyl, R3 is Cl and R1 is Et.
200E Q3 is 6-MeO-3-pyridinyl, R3 is Cl and R^ is Me.
201E Q3 is 6-MeO-3-pyridinyl, R3 is Cl and R1 is CFH2.
202E Q3 is 6-MeO-3-pyridinyl, R3 is Br and R^ is Me.
203E Q3 is 6-MeO-3-pyridinyl, R3 is I and R^ is Me.
204E Q3 is 6-MeO-3-pyridinyl, R3 is Me and R^ is Me.
205E Q3 is 6-MeO-3-pyridinyl, R3 is MeO and R^ is Me.
206E Q3 is 6-MeO-3-pyridinyl, R3 is MeS and R^ is Me.
207E Q3 is 6-MeO-3-pyridinyl, R3 is Et and R^ is Me.
208E Q3 is 6-MeO-3-pyridinyl, R3 is Me and R^ is Et.
209E Q3 is 6-MeO-3-pyridinyl, R3 is Cl and R1 is Et.
210E Q3 is 6-CF3-3-pyridinyl, R3 is Cl and R1 is Me.
211E Q3 is 6-CF3-3-pyridinyl, R3 is Cl and R1 is CFH2. Table Number Row Heading
212E Q3 is 6-CF3-3-pyridinyl, R3 is Br and R* is Me.
213E Q3 is 6-CF3-3-pyridinyl, R3 is I and R^ is Me.
214E Q3 is 6-CF3-3-pyridinyl, R3 is Me and R* is Me.
215E Q3 is 6-CF3-3-pyridinyl, R3 is MeO and R^ is Me.
216E Q3 is 6-CF3-3-pyridinyl, R3 is MeS and R* is Me.
217E Q3 is 6-CF3-3-pyridinyl, R3 is Et and R^ is Me.
218E Q3 is 6-CF3-3-pyridinyl, R3 is Me and R* is Et.
219E Q3 is 6-CF3-3-pyridinyl, R3 is Cl and R1 is Et.
220E Q3 is 6-F-3-pyridinyl, R3 is Cl and R* is Me.
221E Q3 is 6-F-3-pyridinyl, R3 is Cl and R1 is CFH2.
222E Q3 is 6-F-3-pyridinyl, R3 is Br and R^ is Me.
223E Q3 is 6-F-3-pyridinyl, R3 is I and R^ is Me.
224E Q3 is 6-F-3-pyridinyl, R3 is Me and R^ is Me.
225E Q3 is 6-F-3-pyridinyl, R3 is MeO and R^ is Me.
226E Q3 is 6-F-3-pyridinyl, RJ is MeS and R1 is Me.
227E Q3 is 6-F-3-pyridinyl, R3 is Et and R^ is Me.
228E Q3 is 6-F-3-pyridinyl, R3 is Me and R^ is Et.
229E Q3 is 6-F-3-pyridinyl, R3 is Cl and R1 is Et.
230E Q3 is 5-Cl-3-pyridinyl, R3 is Cl and R1 is Me.
23 IE Q3 is 5-Cl-3-pyridinyl, R3 is Cl and R1 is CFH2.
232E Q3 is 5-Cl-3-pyridinyl, R3 is Br and R^ is Me.
233E Q3 is 5-Cl-3-pyridinyl, R3 is I and R^ is Me.
234E Q3 is 5-Cl-3-pyridinyl, R3 is Me and R^ is Me.
235E Q3 is 5-Cl-3-pyridinyl, R3 is MeO and R^ is Me.
236E Q3 is 5-Cl-3-pyridinyl, R3 is MeS and R1 is Me.
237E Q3 is 5-Cl-3-pyridinyl, R3 is Et and R1 is Me.
238E Q3 is 5-Cl-3-pyridinyl, R3 is Me and R^ is Et.
239E Q3 is 5-Cl-3-pyridinyl, R3 is Cl and R1 is Et.
240E Q3 is 5-Me-3-pyridinyl, R3 is Cl and R^ is Me.
241E Q3 is 5-Me-3-pyridinyl, R3 is Cl and R1 is CFH2.
242E Q3 is 5-Me-3-pyridinyl, R3 is Br and R^ is Me.
243E Q3 is 5-Me-3-pyridinyl, R3 is I and R^ is Me.
244E Q3 is 5-Me-3-pyridinyl, R3 is Me and R^ is Me.
245E Q3 is 5-Me-3-pyridinyl, R3 is MeO and R^ is Me.
246E Q3 is 5-Me-3-pyridinyl, R3 is MeS and R^ is Me.
247E Q3 is 5-Me-3-pyridinyl, R3 is Et and R^ is Me.
248E Q3 is 5-Me-3-pyridinyl, R3 is Me and R^ is Et. Table Number Row Heading
249E Q3 is 5-Me-3-pyridinyl, R3 is Cl and R1 is Et.
250E Q3 is 5-MeO-3-pyridinyl, R3 is Cl and R1 is Me.
251E Q3 is 5-MeO-3-pyridinyl, R3 is Cl and R1 is CFH2.
252E Q3 is 5-MeO-3-pyridinyl, R3 is Br and R1 is Me.
253E Q3 is 5-MeO-3-pyridinyl, R3 is I and R^ is Me.
254E Q3 is 5-MeO-3-pyridinyl, R3 is Me and R^ is Me.
255E Q3 is 5-MeO-3-pyridinyl, R3 is MeO and R1 is Me.
256E Q3 is 5-MeO-3-pyridinyl, R3 is MeS and R1 is Me.
257E Q3 is 5-MeO-3-pyridinyl, R3 is Et and R^ is Me.
258E Q3 is 5-MeO-3-pyridinyl, R3 is Me and R1 is Et.
259E Q3 is 5-MeO-3-pyridinyl, R3 is Cl and R1 is Et.
260E Q3 is 5-CF3-3-pyridinyl, R3 is Cl and R1 is Me.
261E Q3 is 5-CF3-3-pyridinyl, R3 is Cl and R1 is CFH2.
262E Q3 is 5-CF3-3-pyridinyl, R3 is Br and R1 is Me.
263E Q3 is 5-CF3-3-pyridinyl, R3 is I and R1 is Me.
264E Q3 is 5-CF3-3-pyridinyl, R3 is Me and R^ is Me.
265E Q3 is 5-CF3-3-pyridinyl, R3 is MeO and R1 is Me.
266E Q3 is 5-CF3-3-pyridinyl, R3 is MeS and R1 is Me.
267E Q3 is 5-CF3-3-pyridinyl, R3 is Et and R1 is Me.
268E Q3 is 5-CF3-3-pyridinyl, R3 is Me and R1 is Et.
269E Q3 is 5-CF3-3-pyridinyl, R3 is Cl and R1 is Et.
270E Q3 is 5-F-3-pyridinyl, R3 is Cl and R1 is Me.
271E Q3 is 5-F-3-pyridinyl, R3 is Cl and R1 is CFH2.
272E Q3 is 5-F-3-pyridinyl, R3 is Br and R^ is Me.
273E Q3 is 5-F-3-pyridinyl, R3 is I and R^ is Me.
274E Q3 is 5-F-3-pyridinyl, R3 is Me and R^ is Me.
275E Q3 is 5-F-3-pyridinyl, R3 is MeO and R^ is Me.
276E Q3 is 5-F-3-pyridinyl, R3 is MeS and R^ is Me.
277E Q3 is 5-F-3-pyridinyl, RJ is Et and R1 is Me.
278E Q3 is 5-F-3-pyridinyl, R3 is Me and R^ is Et.
279E Q3 is 5-F-3-pyridinyl, R3 is Cl and R1 is Et.
280E Q3 is 5-F-3-pyridinyl, R3 is Cl and R1 is CFH2.
281E Q3 is 5-F-3-pyridinyl, R3 is Br and R^ is Me.
282E Q3 is 5-F-3-pyridinyl, R3 is I and R^ is Me.
283E Q3 is 5-F-3-pyridinyl, R3 is Me and R^ is Me.
284E Q3 is 5-F-3-pyridinyl, R3 is MeO and R^ is Me.
285E Q3 is 5-F-3-pyridinyl, R3 is MeS and R1 is Me. Table Number Row Heading
286E Q3 is 5-F-3-pyridinyl, R3 is Et and RI is Me.
287E Q3 is 5-F-3-pyridinyl, R3 is Me and RMs Et.
288E Q3 is 5-F-3-pyridinyl, R3 is Cl and R1 is Et.
289E Q3 is 6-C1-3 -pyridazinyl, R3 is Cl and R1 is CFH2.
290E Q3 is 6-C1-3 -pyridazinyl, R3 is Br and R1 is Me.
291E Q3 is 6-C1-3 -pyridazinyl, R3 is I and RI is Me.
292E Q3 is 6-C1-3 -pyridazinyl, R3 is Me and R^ is Me.
293E Q3 is 6-C1-3 -pyridazinyl, R3 is MeO and RMs Me.
294E Q3 is 6-C1-3 -pyridazinyl, R3 is MeS and R1 is Me.
295E Q3 is 6-C1-3 -pyridazinyl, R3 is Et and R1 is Me.
296E Q3 is 6-C1-3 -pyridazinyl, R3 is Me and R1 is Et.
297E Q3 is 6-C1-3 -pyridazinyl, R3 is Cl and R1 is Et.
298E Q3 is 5-Cl-3-pyridazinyl, R3 is Cl and R1 is CFH2.
299E Q3 is 5-Cl-3-pyridazinyl, R3 is Br and R^ is Me.
300E Q3 is 5-Cl-3-pyridazinyl, R3 is I and R1 is Me.
301E Q3 is 5-Cl-3-pyridazinyl, R3 is Me and R^ is Me.
302E Q3 is 5-Cl-3-pyridazinyl, R3 is MeO and R1 is Me.
303E Q3 is 5-Cl-3-pyridazinyl, R3 is MeS and R1 is Me.
304E Q3 is 5-Cl-3-pyridazinyl, R3 is Et and R1 is Me.
305E Q3 is 5-Cl-3-pyridazinyl, R3 is Me and R^ is Et.
306E Q3 is 5-Cl-3-pyridazinyl, R3 is Cl and R1 is Et.
307E Q3 is 2-C1-5 -pyrimidinyl, R3 is Cl and R1 is CFH2.
308E Q3 is 2-C1-5 -pyrimidinyl, R3 is Br and R1 is Me.
309E Q3 is 2-C1-5 -pyrimidinyl, R3 is I and R1 is Me.
310E Q3 is 2-C1-5 -pyrimidinyl, R3 is Me and R^ is Me.
311E Q3 is 2-C1-5 -pyrimidinyl, R3 is MeO and R1 is Me.
312E Q3 is 2-C1-5 -pyrimidinyl, R3 is MeS and R1 is Me.
313E Q3 is 2-C1-5 -pyrimidinyl, R3 is Et and R^ is Me.
314E Q3 is 2-C1-5 -pyrimidinyl, R3 is Me and R1 is Et.
315E Q3 is 2-C1-5 -pyrimidinyl, R3 is Cl and R1 is Et.
316E Q3 is 2-C1-2 -pyrimidinyl, R3 is Cl and R1 is CFH2.
317E Q3 is 2-C1-2 -pyrimidinyl, R3 is Br and R1 is Me.
318E Q3 is 2-C1-2 -pyrimidinyl, R3 is I and RI is Me.
319E Q3 is 2-C1-2 -pyrimidinyl, R3 is Me and R^ is Me.
320E Q3 is 2-C1-2 -pyrimidinyl, R3 is MeO and RMs Me.
321E Q3 is 2-C1-2 -pyrimidinyl, R3 is MeS and R1 is Me.
322E Q3 is 2-C1-2 -pyrimidinyl, R3 is Et and R1 is Me. Table Number Row Heading
323E Q3 is 2-Cl-2-pyrimidinyl, R3 is Me and R1 is Et.
324E Q3 is 2-Cl-2-pyrimidinyl, R3 is Cl and R1 is Et.
325E Q3 is 5-Me-2-thienyl, R3 is Cl and R1 is CFH2.
326E Q3 is 5-Me-2-thienyl, R3 is Br and R1 is Me.
327E Q3 is 5-Me-2-thienyl, R3 is I and R1 is Me.
328E Q3 is 5-Me-2-thienyl, R3 is Me and R^ is Me.
329E Q3 is 5-Me-2-thienyl, R3 is MeO and R1 is Me.
330E Q3 is 5-Me-2-thienyl, R3 is MeS and R1 is Me.
331E Q3 is 5-Me-2-thienyl, R3 is Et and R1 is Me.
332E Q3 is 5-Me-2-thienyl, R3 is Me and R1 is Et.
333E Q3 is 5-Me-2-thienyl, R3 is Cl and R1 is Et.
334E Q3 is 5-Me-3-thienyl, R3 is Cl and R1 is CFH2.
335E Q3 is 5-Me-3-thienyl, R3 is Br and R1 is Me.
336E Q3 is 5-Me-3-thienyl, R3 is I and R1 is Me.
337E Q3 is 5-Me-3-thienyl, R3 is Me and R^ is Me.
338E Q3 is 5-Me-3-thienyl, R3 is MeO and R1 is Me.
339E Q3 is 5-Me-3-thienyl, R3 is MeS and R1 is Me.
340E Q3 is 5-Me-3-thienyl, R3 is Et and R1 is Me.
341E Q3 is 5-Me-3-thienyl, R3 is Me and R1 is Et.
342E Q3 is 5-Me-3-thienyl, R3 is Cl and R1 is Et.
343E Q3 is l-Me-l//-pyrazol-3-yl, R3 is Cl and R1 is CFH2.
344E Q3 is l-Me-l//-pyrazol-3-yl, R3 is Br and R1 is Me.
345E Q3 is l-Me-l//-pyrazol-3-yl, R3 is I and R1 is Me.
346E Q3 is l-Me-l//-pyrazol-3-yl, R3 is Me and R^ is Me.
347E Q3 is l-Me-l//-pyrazol-3-yl, R3 is MeO and R1 is Me.
348E Q3 is l-Me-l//-pyrazol-3-yl, R3 is MeS and R1 is Me.
349E Q3 is l-Me-l//-pyrazol-3-yl, R3 is Et and R1 is Me.
350E Q3 is l-Me-l//-pyrazol-3-yl,, R3 is Me and R1 is Et.
351E Q3 is l-Me-l//-pyrazol-3-yl, R3 is Cl and R1 is Et.
352E Q3 is l-Me-l//-pyrazol-4-yl, R3 is Cl and R1 is CFH2.
353E Q3 is l-Me-l//-pyrazol-4-yl, R3 is Br and R1 is Me.
354E Q3 is l-Me-l//-pyrazol-4-yl, R3 is I and R^ is Me.
355E Q3 is l-Me-l//-pyrazol-4-yl, R3 is Me and R^ is Me.
356E Q3 is l-Me-l//-pyrazol-4-yl, R3 is MeO and R1 is Me.
357E Q3 is l-Me-l//-pyrazol-4-yl, R3 is MeS and R1 is Me.
358E Q3 is l-Me-l//-pyrazol-4-yl, R3 is Et and R1 is Me.
359E Q3 is l-Me-l//-pyrazol-4-yl, R3 is Me and R1 is Et. Table Number Row Heading
360E Q3 is l-Me-l//-pyrazol-4-yl, R3 is Cl and R1 is Et.
361E Q3 is 2-Me-5-thiazolyl, R3 is Cl and R1 is CFH2.
362E Q3 is 2-Me-5-thiazolyl, R3 is Br and R1 is Me.
363E Q3 is 2-Me-5-thiazolyl, R3 is I and R1 is Me.
364E Q3 is 2-Me-5-thiazolyl, R3 is Me and R1 is Me.
365E Q3 is 2-Me-5-thiazolyl, R3 is MeO and R1 is Me.
366E Q3 is 2-Me-5-thiazolyl, R3 is MeS and R1 is Me.
367E Q3 is 2-Me-5-thiazolyl, R3 is Et and R1 is Me.
368E Q3 is 2-Me-5-thiazolyl, R3 is Me and R1 is Et.
369E Q3 is 2-Me-5-thiazolyl, R3 is Cl and R1 is Et.
370E Q3 is 2-Cl-5-thiazolyl, R3 is Cl and R1 is CFH2.
371E Q3 is 2-Cl-5-thiazolyl, R3 is Br and R1 is Me.
372E Q3 is 2-Cl-5-thiazolyl, R3 is I and R1 is Me.
373E Q3 is 2-Cl-5-thiazolyl, R3 is Me and R1 is Me.
374E Q3 is 2-Cl-5-thiazolyl, R3 is MeO and R1 is Me.
375E Q3 is 2-Cl-5-thiazolyl, R3 is MeS and R1 is Me.
376E Q3 is 2-Cl-5-thiazolyl, R3 is Et and R1 is Me.
377E Q3 is 2-Cl-5-thiazolyl, R3 is Me and R1 is Et.
378E Q3 is 2-Cl-5-thiazolyl, R3 is Cl and R1 is Et.
379E Q3 is 5-Me-3-isothiazolyl, R3 is Cl and R1 is CFH2.
380E Q3 is 5-Me-3-isothiazolyl, R3 is Br and R^ is Me.
381E Q3 is 5-Me-3-isothiazolyl, R3 is I and R^ is Me.
382E Q3 is 5-Me-3-isothiazolyl, R3 is Me and R^ is Me.
383E Q3 is 5-Me-3-isothiazolyl, R3 is MeO and R^ is Me.
384E Q3 is 5-Me-3-isothiazolyl, R3 is MeS and R^ is Me.
385E Q3 is 5-Me-3-isothiazolyl, R3 is Et and R^ is Me.
386E Q3 is 5-Me-3-isothiazolyl, R3 is Me and R^ is Et.
387E Q3 is 5-Me-3-isothiazolyl, R3 is Cl and R1 is Et.
Figure imgf000155_0001
Q1 is 4-Cl-Ph, R3 is Cl and R1 is Me.
Figure imgf000156_0001
Figure imgf000156_0002
The present disclosure also includes Tables IF through 934F, each of which is constructed the same as Table 6 above except that the row heading in Table 6 (i.e. "Q1 is 4-Cl-Ph, R3 is Cl and R1 is Me") is replaced with the respective row heading shown below. Thus, for example, in Table IF the row heading is "Q3 is 4-Cl-Ph, R3 is Cl and R1 is CFH2" and (R5c)D is as defined in Table 6 above. Tables 2F through 934F are constructed similarly.
Table Number Row Heading
IF Q3 is 4-Cl-Ph, R3 is Cl and R1 is CFH2
2F Q3 is 4-Cl-Ph, R3 is Br and R1 is Me.
3F Q3 is 4-Cl-Ph, R3 is I and RI is Me.
4F Q3 is 4-Cl-Ph, R3 is Me and R^ is Me.
5F Q3 is 4-Cl-Ph, R3 is MeO and R^ is Me.
6F Q3 is 4-Cl-Ph, R3 is MeS and R1 is Me.
7F Q3 is 4-Cl-Ph, R3 is Et and R1 is Me.
8F Q3 is 4-Cl-Ph, R3 is Me and R1 is Et.
9F Q3 is 4-Cl-Ph, R3 is Cl and R1 is Et.
1OF Q3 is 3 -Cl-Ph, R3 is Cl and R1 is Me.
HF Q3 is 3 -Cl-Ph, R3 is Cl and R1 is CFH2.
12F Q3 is 3 -Cl-Ph, R3 is Br and R1 is Me.
13F Q3 is 3 -Cl-Ph, R3 is I and RI is Me.
14F Q3 is 3 -Cl-Ph, R3 is Me and R^ is Me.
15F Q3 is 3 -Cl-Ph, R3 is MeO and R^ is Me.
16F Q3 is 3 -Cl-Ph, R3 is MeS and R1 is Me.
17F Q3 is 3 -Cl-Ph, R3 is Et and R1 is Me.
18F Q3 is 3 -Cl-Ph, R3 is Me and R1 is Et. Table Number Row Heading
19F Q3 is 3 -Cl-Ph, R3 is Cl and R1 is Et.
2OF Q3 is 4-F-Ph, R3 is Cl and R1 is Me.
21F Q3 is 4-F-Ph, R3 is Cl and R1 is CFH2.
22F Q3 is 4-F-Ph, R3 is Br and R1 is Me.
23F Q3 is 4-F-Ph, R3 is I and R1 is Me.
24F Q3 is 4-F-Ph, R3 is Me and R1 is Me.
25F Q3 is 4-F-Ph, R3 is MeO and R1 is Me.
26F Q3 is 4-F-Ph, R3 is MeS and R1 is Me.
27F Q3 is 4-F-Ph, R3 is Et and R1 is Me.
28F Q3 is 4-F-Ph, R3 is Me and R1 is Et.
29F Q3 is 4-F-Ph, R3 is Cl and R1 is Et.
3OF Q3 is 3-F-Ph, R3 is Cl and R1 is Me.
31F Q3 is 3-F-Ph, R3 is Cl and R1 is CFH2.
32F Q3 is 3-F-Ph, R3 is Br and R1 is Me.
33F Q3 is 3-F-Ph, R3 is I and R1 is Me.
34F Q3 is 3-F-Ph, R3 is Me and R1 is Me.
35F Q3 is 3-F-Ph, R3 is MeO and R1 is Me.
36F Q3 is 3-F-Ph, R3 is MeS and R1 is Me.
37F Q3 is 3-F-Ph, R3 is Et and R1 is Me.
38F Q3 is 3-F-Ph, R3 is Me and R1 is Et.
39F Q3 is 3-F-Ph, R3 is Cl and R1 is Et.
4OF Q3 is 3-CF2HO-Ph, R3 is Cl and R1 is Me.
41F Q3 is 3-CF2HO-Ph, R3 is Cl and R1 is CFH2.
42F Q3 is 3-CF2HO-Ph, R3 is Br and R1 is Me.
43F Q3 is 3-CF2HO-Ph, R3 is I and R1 is Me.
44F Q3 is 3-CF2HO-Ph, R3 is Me and R1 is Me.
45F Q3 is 3-CF2HO-Ph, R3 is MeO and R1 is Me.
46F Q3 is 3-CF2HO-Ph, R3 is MeS and R1 is Me.
47F Q3 is 3-CF2HO-Ph, R3 is Et and R1 is Me.
48F Q3 is 3-CF2HO-Ph, R3 is Me and R1 is Et.
49F Q3 is 3-CF2HO-Ph, R3 is Cl and R1 is Et.
5OF Q3 is 4-Me-Ph, R3 is Cl and R1 is Me.
51F Q3 is 4-Me-Ph, R3 is Cl and R1 is CFH2.
52F Q3 is 4-Me-Ph, R3 is Br and R1 is Me.
53F Q3 is 4-Me-Ph, R3 is I and R1 is Me.
54F Q3 is 4-Me-Ph, R3 is Me and R1 is Me.
55F Q3 is 4-Me-Ph, R3 is MeO and R1 is Me. Table Number Row Heading
56F Q3 is 4-Me-Ph, R3 is MeS and R1 is Me.
57F Q3 is 4-Me-Ph, R3 is Et and R1 is Me.
58F Q3 is 4-Me-Ph, R3 is Me and R1 is Et.
59F Q3 is 4-Me-Ph, R3 is Cl and R1 is Et.
6OF Q3 is 3-Me-Ph, R3 is Cl and R1 is Me.
61F Q3 is 3-Me-Ph, R3 is Cl and R1 is CFH2.
62F Q3 is 3-Me-Ph, R3 is Br and R1 is Me.
63F Q3 is 3-Me-Ph, R3 is I and R1 is Me.
64F Q3 is 3-Me-Ph, R3 is Me and R1 is Me.
65F Q3 is 3-Me-Ph, R3 is MeO and R1 is Me.
66F Q3 is 3-Me-Ph, R3 is MeS and R1 is Me.
67F Q3 is 3-Me-Ph, R3 is Et and R1 is Me.
68F Q3 is 3-Me-Ph, R3 is Me and R1 is Et.
69F Q3 is 3-Me-Ph, R3 is Cl and R1 is Et.
7OF Q3 is 4-Et-Ph, R3 is Cl and R1 is Me.
71F Q3 is 4-Et-Ph, R3 is Cl and R1 is CFH2.
72F Q3 is 4-Et-Ph, R3 is Br and R1 is Me.
73F Q3 is 4-Et-Ph, R3 is I and R1 is Me.
74F Q3 is 4-Et-Ph, R3 is Me and R1 is Me.
75F Q3 is 4-Et-Ph, R3 is MeO and R1 is Me.
76F Q3 is 4-Et-Ph, R3 is MeS and R1 is Me.
77F Q3 is 4-Et-Ph, R3 is Et and R1 is Me.
78F Q3 is 4-Et-Ph, R3 is Me and R1 is Et.
79F Q3 is 4-Et-Ph, R3 is Cl and R1 is Et.
8OF Q3 is 4-Cl-3-F-Ph, R3 is Cl and R1 is Me.
81F Q3 is 4-Cl-3-F-Ph, R3 is Cl and R1 is CFH2.
82F Q3 is 4-Cl-3-F-Ph, R3 is Br and R1 is Me.
83F Q3 is 4-Cl-3-F-Ph, R3 is I and R1 is Me.
84F Q3 is 4-Cl-3-F-Ph, R3 is Me and R1 is Me.
85F Q3 is 4-Cl-3-F-Ph, R3 is MeO and R1 is Me.
86F Q3 is 4-Cl-3-F-Ph, R3 is MeS and R1 is Me.
87F Q3 is 4-Cl-3-F-Ph, R3 is Et and R1 is Me.
88F Q3 is 4-Cl-3-F-Ph, R3 is Me and R1 is Et.
89F Q3 is 4-Cl-3-F-Ph, R3 is Cl and R1 is Et.
9OF Q3 is 2-Cl, 4-F-Ph, R3 is Cl and R1 is Me.
91F Q3 is 2-Cl, 4-F-Ph, R3 is Cl and R1 is CFH2.
92F Q3 is 2-Cl, 4-F-Ph, R3 is Br and R1 is Me. Table Number Row Heading
93F Q3 is 2-Cl, 4-F-Ph, R3 is I and R1 is Me.
94F Q3 is 2-Cl, 4-F-Ph, R3 is Me and R1 is Me.
95F Q3 is 2-Cl, 4-F-Ph, R3 is MeO and R1 is Me.
96F Q3 is 2-Cl, 4-F-Ph, R3 is MeS and R1 is Me.
97F Q3 is 2-Cl, 4-F-Ph, R3 is Et and R1 is Me.
98F Q3 is 2-Cl, 4-F-Ph, R3 is Me and R1 is Et.
99F Q3 is 2-Cl, 4-F-Ph, R3 is Cl and R1 is Et.
IOOF Q3 is 4-F, 3-Me-Ph, R3 is Cl and R1 is Me.
101F Q3 is 4-F, 3-Me-Ph, R3 is Cl and R1 is CFH2.
102F Q3 is 4-F, 3-Me-Ph, R3 is Br and R^ is Me.
103F Q3 is 4-F, 3-Me-Ph, R3 is I and R^ is Me.
104F Q3 is 4-F, 3-Me-Ph, R3 is Me and R^ is Me.
105F Q3 is 4-F, 3-Me-Ph, R3 is MeO and R^ is Me.
106F Q3 is 4-F, 3-Me-Ph, R3 is MeS and R^ is Me.
107F Q3 is 4-F, 3-Me-Ph, R3 is Et and R^ is Me.
108F Q3 is 4-F, 3-Me-Ph, R3 is Me and RMs Et.
109F Q3 is 4-F, 3-Me-Ph, R3 is Cl and R1 is Et.
HOF Q3 is 3,4-di-F-Ph, R3 is Cl and R1 is Me.
H iF Q3 is 3,4-di-F-Ph, R3 is Cl and R1 is CFH2.
112F Q3 is 3,4-di-F-Ph, R3 is Br and R1 is Me.
113F Q3 is 3,4-di-F-Ph, R3 is I and RI is Me.
114F Q3 is 3,4-di-F-Ph, R3 is Me and R^ is Me.
115F Q3 is 3,4-di-F-Ph, R3 is MeO and R^ is Me.
116F Q3 is 3,4-di-F-Ph, R3 is MeS and R1 is Me.
117F Q3 is 3,4-di-F-Ph, R3 is Et and R1 is Me.
118F Q3 is 3,4-di-F-Ph, R3 is Me and R1 is Et.
119F Q3 is 3,4-di-F-Ph, R3 is Cl and R1 is Et.
120F Q3 is 3,4-di-Cl-Ph, R3 is Cl and R1 is Me.
121F Q3 is 3,4-di-Cl-Ph, R3 is Cl and R1 is CFH2.
122F Q3 is 3,4-di-Cl-Ph, R3 is Br and R1 is Me.
123F Q3 is 3,4-di-Cl-Ph, R3 is I and R1 is Me.
124F Q3 is 3,4-di-Cl-Ph, R3 is Me and R1 is Me.
125F Q3 is 3,4-di-Cl-Ph, R3 is MeO and R1 is Me.
126F Q3 is 3,4-di-Cl-Ph, R3 is MeS and R1 is Me.
127F Q3 is 3,4-di-Cl-Ph, R3 is Et and R1 is Me.
128F Q3 is 3,4-di-Cl-Ph, R3 is Me and R1 is Et.
129F Q3 is 3,4-di-Cl-Ph, R3 is Cl and R1 is Et. Table Number Row Heading
130F Q3 is 3,5-di-MeO-Ph, R3 is Cl and RI is Me.
131F Q3 is 3,5-di-MeO-Ph, R3 is Cl and R1 is CFH2.
132F Q3 is 3,5-di-MeO-Ph, R3 is Br and RI is Me.
133F Q3 is 3,5-di-MeO-Ph, R3 is I and R1 is Me.
134F Q3 is 3,5-di-MeO-Ph, R3 is Mc ; and R^ is Me.
135F Q3 is 3,5-di-MeO-Ph, R3 is MeO and R1 is Me.
136F Q3 is 3,5-di-MeO-Ph, R3 is MeS and R1 is Me.
137F Q3 is 3,5-di-MeO-Ph, R3 is Et and RI is Me.
138F Q3 is 3,5-di-MeO-Ph, R3 is Mt ; and R1 is Et.
139F Q3 is 3,5-di-MeO-Ph, R3 is Cl and R1 is Et.
140F Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Cl and R1 is Me.
141F Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Cl and R1 is CFH2.
142F Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Br and R^ is Me.
143F Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is I and R^ is Me.
144F Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Me and R^ is Me.
145F Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is MeO and R^ is Me.
146F Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is MeS and R^ is Me.
147F Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Et and R^ is Me.
148F Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Me and R^ is Et.
149F Q3 is 2-Cl, 3,5-di-MeO-Ph, R3 is Cl and R1 is Et.
150F Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Cl and R1 is Me.
151F Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Cl and R1 is CFH2.
152F Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Br and R^ is Me.
153F Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is I and R^ is Me.
154F Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Me and R^ is Me.
155F Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is MeO and R^ is Me.
156F Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is MeS and R^ is Me.
157F Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Et and R^ is Me.
158F Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Me and R^ is Et.
159F Q3 is 4-Cl, 3,5-di-MeO-Ph, R3 is Cl and R1 is Et.
160F Q3 is 4-Cl-Bn, R3 is Cl and R1 is Me.
161F Q3 is 4-Cl-Bn, R3 is Cl and R1 is CFH2.
162F Q3 is 4-Cl-Bn, R3 is Br and R1 is Me.
163F Q3 is 4-Cl-Bn, R3 is I and R1 is Me.
164F Q3 is 4-Cl-Bn, R3 is Me and R1 is Me.
165F Q3 is 4-Cl-Bn, R3 is MeO and R1 is Me.
166F Q3 is 4-Cl-Bn, R3 is MeS and R1 is Me. Table Number Row Heading
167F Q3 is 4-Cl-Bn, R3 is Et and R1 is Me.
168F Q3 is 4-Cl-Bn, R3 is Me and R1 is Et.
169F Q3 is 4-Cl-Bn, R3 is Cl and R1 is Et.
170F Q3 is 4-F-Bn, R3 is Cl and R1 is Me.
171F Q3 is 4-F-Bn, R3 is Cl and R1 is CFH2.
172F Q3 is 4-F-Bn, R3 is Br and R1 is Me.
173F Q3 is 4-F-Bn, R3 is I and R1 is Me.
174F Q3 is 4-F-Bn, R3 is Me and R1 is Me.
175F Q3 is 4-F-Bn, R3 is MeO and R1 is Me.
176F Q3 is 4-F-Bn, R3 is MeS and R1 is Me.
177F Q3 is 4-F-Bn, R3 is Et and R1 is Me.
178F Q3 is 4-F-Bn, R3 is Me and R1 is Et.
179F Q3 is 4-F-Bn, R3 is Cl and R1 is Et.
180F Q3 is 6-Cl-3-pyridinyl, R3 is Cl and R1 is Me.
181F Q3 is 6-Cl-3-pyridinyl, R3 is Cl and R1 is CFH2.
182F Q3 is 6-Cl-3-pyridinyl, R3 is Br and R1 is Me.
183F Q3 is 6-Cl-3-pyridinyl, R3 is I and R1 is Me.
184F Q3 is 6-Cl-3-pyridinyl, R3 is Me and R1 is Me.
185F Q3 is 6-Cl-3-pyridinyl, R3 is MeO and R1 is Me.
186F Q3 is 6-Cl-3-pyridinyl, R3 is MeS and R1 is Me.
187F Q3 is 6-Cl-3-pyridinyl, R3 is Et and R1 is Me.
188F Q3 is 6-Cl-3-pyridinyl, R3 is Me and R1 is Et.
189F Q3 is 6-Cl-3-pyridinyl, R3 is Cl and R1 is Et.
190F Q3 is 6-Me-3-pyridinyl, R3 is Cl and R1 is Me.
191F Q3 is 6-Me-3-pyridinyl, R3 is Cl and R1 is CFH2.
192F Q3 is 6-Me-3-pyridinyl, R3 is Br and R^ is Me.
193F Q3 is 6-Me-3-pyridinyl, R3 is I and R^ is Me.
194F Q3 is 6-Me-3-pyridinyl, R3 is Me and R^ is Me.
195F Q3 is 6-Me-3-pyridinyl, R3 is MeO and R^ is Me.
196F Q3 is 6-Me-3-pyridinyl, R3 is MeS and R^ is Me.
197F Q3 is 6-Me-3-pyridinyl, R3 is Et and R^ is Me.
198F Q3 is 6-Me-3-pyridinyl, R3 is Me and R^ is Et.
199F Q3 is 6-Me-3-pyridinyl, R3 is Cl and R1 is Et.
200F Q3 is 6-MeO-3-pyridinyl, R3 is Cl and R1 is Me.
201F Q3 is 6-MeO-3-pyridinyl, R3 is Cl and R1 is CFH2.
202F Q3 is 6-MeO-3-pyridinyl, R3 is Br and R1 is Me.
203F Q3 is 6-MeO-3-pyridinyl, R3 is I and R^ is Me. Table Number Row Heading
204F Q3 is 6-MeO-3-pyridinyl, R3 is Me and R* is Me.
205F Q3 is 6-MeO-3-pyridinyl, R3 is MeO and R^ is Me.
206F Q3 is 6-MeO-3-pyridinyl, R3 is MeS and R^ is Me.
207F Q3 is 6-MeO-3-pyridinyl, R3 is Et and R^ is Me.
208F Q3 is 6-MeO-3-pyridinyl, R3 is Me and R^ is Et.
209F Q3 is 6-MeO-3-pyridinyl, R3 is Cl and R1 is Et.
210F Q3 is 6-CF3-3-pyridinyl, R3 is Cl and R1 is Me.
211F Q3 is 6-CF3-3-pyridinyl, R3 is Cl and R1 is CFH2.
212F Q3 is 6-CF3-3-pyridinyl, R3 is Br and R^ is Me.
213F Q3 is 6-CF3-3-pyridinyl, R3 is I and R^ is Me.
214F Q3 is 6-CF3-3-pyridinyl, R3 is Me and R^ is Me.
215F Q3 is 6-CF3-3-pyridinyl, R3 is MeO and R^ is Me.
216F Q3 is 6-CF3-3-pyridinyl, RJ is MeS and R1 is Me.
217F Q3 is 6-CF3-3-pyridinyl, R3 is Et and R^ is Me.
218F Q3 is 6-CF3-3-pyridinyl, R3 is Me and R^ is Et.
219F Q3 is 6-CF3-3-pyridinyl, R3 is Cl and R1 is Et.
220F Q3 is 6-F-3-pyridinyl, R3 is Cl and R^ is Me.
221F Q3 is 6-F-3-pyridinyl, R3 is Cl and R1 is CFH2.
222F Q3 is 6-F-3-pyridinyl, R3 is Br and R^ is Me.
223F Q3 is 6-F-3-pyridinyl, R3 is I and R^ is Me.
224F Q3 is 6-F-3-pyridinyl, R3 is Me and R^ is Me.
225F Q3 is 6-F-3-pyridinyl, R3 is MeO and R^ is Me.
226F Q3 is 6-F-3-pyridinyl, RJ is MeS and R1 is Me.
227F Q3 is 6-F-3-pyridinyl, R3 is Et and R^ is Me.
228F Q3 is 6-F-3-pyridinyl, R3 is Me and R^ is Et.
229F Q3 is 6-F-3-pyridinyl, R3 is Cl and R1 is Et.
230F Q3 is 5-Cl-3-pyridinyl, R3 is Cl and R1 is Me.
231F Q3 is 5-Cl-3-pyridinyl, R3 is Cl and R1 is CFH2.
232F Q3 is 5-Cl-3-pyridinyl, R3 is Br and R^ is Me.
233F Q3 is 5-Cl-3-pyridinyl, R3 is I and R^ is Me.
234F Q3 is 5-Cl-3-pyridinyl, R3 is Me and R^ is Me.
235F Q3 is 5-Cl-3-pyridinyl, R3 is MeO and R^ is Me.
236F Q3 is 5-Cl-3-pyridinyl, R3 is MeS and R1 is Me.
237F Q3 is 5-Cl-3-pyridinyl, R3 is Et and R1 is Me.
238F Q3 is 5-Cl-3-pyridinyl, R3 is Me and R1 is Et.
239F Q3 is 5-Cl-3-pyridinyl, R3 is Cl and R1 is Et.
240F Q3 is 5-Me-3-pyridinyl, R3 is Cl and R^ is Me. Table Number Row Heading
241F Q3 is 5-Me-3-pyridinyl, R3 is Cl and R1 is CFH2.
242F Q3 is 5-Me-3-pyridinyl, R3 is Br and R^ is Me.
243F Q3 is 5-Me-3-pyridinyl, R3 is I and R^ is Me.
244F Q3 is 5-Me-3-pyridinyl, R3 is Me and R^ is Me.
245F Q3 is 5-Me-3-pyridinyl, R3 is MeO and R^ is Me.
246F Q3 is 5-Me-3-pyridinyl, R3 is MeS and R^ is Me.
247F Q3 is 5-Me-3-pyridinyl, R3 is Et and R^ is Me.
248F Q3 is 5-Me-3-pyridinyl, R3 is Me and R^ is Et.
249F Q3 is 5-Me-3-pyridinyl, R3 is Cl and R1 is Et.
250F Q3 is 5-MeO-3-pyridinyl, R3 is Cl and R1 is Me.
251F Q3 is 5-MeO-3-pyridinyl, R3 is Cl and R1 is CFH2.
252F Q3 is 5-MeO-3-pyridinyl, R3 is Br and R^ is Me.
253F Q3 is 5-MeO-3-pyridinyl, R3 is I and R^ is Me.
254F Q3 is 5-MeO-3-pyridinyl, R3 is Me and R^ is Me.
255F Q3 is 5-MeO-3-pyridinyl, R3 is MeO and R^ is Me.
256F Q3 is 5-MeO-3-pyridinyl, R3 is MeS and R^ is Me.
257F Q3 is 5-MeO-3-pyridinyl, R3 is Et and R^ is Me.
258F Q3 is 5-MeO-3-pyridinyl, R3 is Me and R^ is Et.
259F Q3 is 5-MeO-3-pyridinyl, R3 is Cl and R1 is Et.
260F Q3 is 5-CF3-3-pyridinyl, R3 is Cl and R1 is Me.
261F Q3 is 5-CF3-3-pyridinyl, R3 is Cl and R1 is CFH2.
262F Q3 is 5-CF3-3-pyridinyl, R3 is Br and R^ is Me.
263F Q3 is 5-CF3-3-pyridinyl, R3 is I and R^ is Me.
264F Q3 is 5-CF3-3-pyridinyl, R3 is Me and R^ is Me.
265F Q3 is 5-CF3-3-pyridinyl, R3 is MeO and R^ is Me.
266F Q3 is 5-CF3-3-pyridinyl, R3 is MeS and R^ is Me.
267F Q3 is 5-CF3-3-pyridinyl, R3 is Et and R^ is Me.
268F Q3 is 5-CF3-3-pyridinyl, R3 is Me and R^ is Et.
269F Q3 is 5-CF3-3-pyridinyl, R3 is Cl and R1 is Et.
270F Q3 is 5-F-3-pyridinyl, R3 is Cl and R^ is Me.
271F Q3 is 5-F-3-pyridinyl, R3 is Cl and R1 is CFH2.
272F Q3 is 5-F-3-pyridinyl, R3 is Br and R^ is Me.
273F Q3 is 5-F-3-pyridinyl, R3 is I and R^ is Me.
274F Q3 is 5-F-3-pyridinyl, R3 is Me and R^ is Me.
275F Q3 is 5-F-3-pyridinyl, R3 is MeO and R^ is Me.
276F Q3 is 5-F-3-pyridinyl, R3 is MeS and R^ is Me.
277F Q3 is 5-F-3-pyridinyl, R3 is Et and R^ is Me. Table Number Row Heading
278F Q3 is 5-F-3-pyridinyl, R3 is Me and R1 is Et.
279F Q3 is 5-F-3-pyridinyl, R3 is Cl and R1 is Et.
280F Q3 is 5-F-3-pyridinyl, R3 is Cl and R1 is CFH2.
281F Q3 is 5-F-3-pyridinyl, R3 is Br and R^ is Me.
282F Q3 is 5-F-3-pyridinyl, R3 is I and R^ is Me.
283F Q3 is 5-F-3-pyridinyl, R3 is Me and RI is Me.
284F Q3 is 5-F-3-pyridinyl, R3 is MeO and RMs Me.
285F Q3 is 5-F-3-pyridinyl, R3 is MeS and R^ is Me.
286F Q3 is 5-F-3-pyridinyl, R3 is Et and RI is Me.
287F Q3 is 5-F-3-pyridinyl, R3 is Me and RMs Et.
288F Q3 is 5-F-3-pyridinyl, R3 is Cl and R1 is Et.
289F Q3 is 6-C1-3 -pyridazinyl, R3 is Cl and R1 is CFH2.
290F Q3 is 6-C1-3 -pyridazinyl, R3 is Br and R1 is Me.
291F Q3 is 6-C1-3 -pyridazinyl, R3 is I and RI is Me.
292F Q3 is 6-C1-3 -pyridazinyl, R3 is Me and R^ is Me.
293F Q3 is 6-C1-3 -pyridazinyl, R3 is MeO and RMs Me.
294F Q3 is 6-C1-3 -pyridazinyl, R3 is MeS and R1 is Me.
295F Q3 is 6-C1-3 -pyridazinyl, R3 is Et and R1 is Me.
296F Q3 is 6-C1-3 -pyridazinyl, R3 is Me and R1 is Et.
297F Q3 is 6-C1-3 -pyridazinyl, R3 is Cl and R1 is Et.
298F Q3 is 5-Cl-3-pyridazinyl, R3 is Cl and R1 is CFH2.
299F Q3 is 5-Cl-3-pyridazinyl, R3 is Br and R^ is Me.
300F Q3 is 5-Cl-3-pyridazinyl, R3 is I and R1 is Me.
301F Q3 is 5-Cl-3-pyridazinyl, R3 is Me and R^ is Me.
302F Q3 is 5-Cl-3-pyridazinyl, R3 is MeO and R1 is Me.
303F Q3 is 5-Cl-3-pyridazinyl, R3 is MeS and R1 is Me.
304F Q3 is 5-Cl-3-pyridazinyl, R3 is Et and R1 is Me.
305F Q3 is 5-Cl-3-pyridazinyl, R3 is Me and R^ is Et.
306F Q3 is 5-Cl-3-pyridazinyl, R3 is Cl and R1 is Et.
307F Q3 is 2-Cl-5-pyrimidinyl, R3 is Cl and R1 is CFH2.
308F Q3 is 2-Cl-5-pyrimidinyl, R3 is Br and R1 is Me.
309F Q3 is 2-Cl-5-pyrimidinyl, R3 is I and R1 is Me.
310F Q3 is 2-Cl-5-pyrimidinyl, R3 is Me and R^ is Me.
311F Q3 is 2-Cl-5-pyrimidinyl, R3 is MeO and R1 is Me.
312F Q3 is 2-Cl-5-pyrimidinyl, R3 is MeS and R1 is Me.
313F Q3 is 2-Cl-5-pyrimidinyl, R3 is Et and R^ is Me.
314F Q3 is 2-Cl-5-pyrimidinyl, R3 is Me and R1 is Et. Table Number Row Heading
315F Q3 is 2-Cl-5-pyrimidinyl, R3 is Cl and R1 is Et.
316F Q3 is 2-Cl-2-pyrimidinyl, R3 is Cl and R1 is CFH2.
317F Q3 is 2-Cl-2-pyrimidinyl, R3 is Br and R1 is Me.
318F Q3 is 2-Cl-2-pyrimidinyl, R3 is I and R1 is Me.
319F Q3 is 2-Cl-2-pyrimidinyl, R3 is Me and R^ is Me.
320F Q3 is 2-Cl-2-pyrimidinyl, R3 is MeO and R1 is Me.
321F Q3 is 2-Cl-2-pyrimidinyl, R3 is MeS and R1 is Me.
322F Q3 is 2-Cl-2-pyrimidinyl, R3 is Et and R1 is Me.
323F Q3 is 2-Cl-2-pyrimidinyl, R3 is Me and R1 is Et.
324F Q3 is 2-Cl-2-pyrimidinyl, R3 is Cl and R1 is Et.
325F Q3 is 5-Me-2-thienyl, R3 is Cl and R1 is CFH2.
326F Q3 is 5-Me-2-thienyl, R3 is Br and R1 is Me.
327F Q3 is 5-Me-2-thienyl, R3 is I and R1 is Me.
328F Q3 is 5-Me-2-thienyl, R3 is Me and R1 is Me.
329F Q3 is 5-Me-2-thienyl, R3 is MeO and R1 is Me.
330F Q3 is 5-Me-2-thienyl, R3 is MeS and R1 is Me.
331F Q3 is 5-Me-2-thienyl, R3 is Et and R1 is Me.
332F Q3 is 5-Me-2-thienyl, R3 is Me and R1 is Et.
333F Q3 is 5-Me-2-thienyl, R3 is Cl and R1 is Et.
334F Q3 is 5-Me-3-thienyl, R3 is Cl and R1 is CFH2.
335F Q3 is 5-Me-3-thienyl, R3 is Br and R1 is Me.
336F Q3 is 5-Me-3-thienyl, R3 is I and R1 is Me.
337F Q3 is 5-Me-3-thienyl, R3 is Me and R^ is Me.
338F Q3 is 5-Me-3-thienyl, R3 is MeO and R1 is Me.
339F Q3 is 5-Me-3-thienyl, R3 is MeS and R1 is Me.
340F Q3 is 5-Me-3-thienyl, R3 is Et and R1 is Me.
341F Q3 is 5-Me-3-thienyl, R3 is Me and R1 is Et.
342F Q3 is 5-Me-3-thienyl, R3 is Cl and R1 is Et.
343F Q3 is l-Me-l//-pyrazol-3-yl, R3 is Cl and R1 is CFH2.
344F Q3 is l-Me-l//-pyrazol-3-yl, R3 is Br and R1 is Me.
345F Q3 is l-Me-l//-pyrazol-3-yl, R3 is I and R1 is Me.
346F Q3 is l-Me-l//-pyrazol-3-yl, R3 is Me and R^ is Me.
347F Q3 is l-Me-l//-pyrazol-3-yl, R3 is MeO and R1 is Me.
348F Q3 is l-Me-l//-pyrazol-3-yl, R3 is MeS and R1 is Me.
349F Q3 is l-Me-l//-pyrazol-3-yl, R3 is Et and R1 is Me.
350F Q3 is l-Me-l//-pyrazol-3-yl,, R3 is Me and R1 is Et.
351F Q3 is l-Me-l//-pyrazol-3-yl, R3 is Cl and R1 is Et. Table Number Row Heading
352F Q3 is l-Me-l//-pyrazol-4-yl, R3 is Cl and R1 is CFH2.
353F Q3 is l-Me-l//-pyrazol-4-yl, R3 is Br and R* is Me.
354F Q3 is l-Me-l//-pyrazol-4-yl, R3 is I and R^ is Me.
355F Q3 is l-Me-l//-pyrazol-4-yl, R3 is Me and R* is Me.
356F Q3 is l-Me-l//-pyrazol-4-yl, R3 is MeO and R1 is Me.
357F Q3 is l-Me-l//-pyrazol-4-yl, R3 is MeS and R^ is Me.
358F Q3 is l-Me-l//-pyrazol-4-yl, R3 is Et and R1 is Me.
359F Q3 is l-Me-l//-pyrazol-4-yl, R3 is Me and R* is Et.
360F Q3 is l-Me-l//-pyrazol-4-yl, R3 is Cl and R1 is Et.
361F Q3 is 2-Me-5-thiazolyl, R3 is Cl and R1 is CFH2.
362F Q3 is 2-Me-5-thiazolyl, R3 is Br and R1 is Me.
363F Q3 is 2-Me-5-thiazolyl, R3 is I and R1 is Me.
364F Q3 is 2-Me-5-thiazolyl, R3 is Me and R^ is Me.
365F Q3 is 2-Me-5-thiazolyl, R3 is MeO and R1 is Me.
366F Q3 is 2-Me-5-thiazolyl, R3 is MeS and R1 is Me.
367F Q3 is 2-Me-5-thiazolyl, R3 is Et and R1 is Me.
368F Q3 is 2-Me-5-thiazolyl, R3 is Me and R1 is Et.
369F Q3 is 2-Me-5-thiazolyl, R3 is Cl and R1 is Et.
370F Q3 is 2-Cl-5-thiazolyl, R3 is Cl and R1 is CFH2.
371F Q3 is 2-Cl-5-thiazolyl, R3 is Br and R1 is Me.
372F Q3 is 2-Cl-5-thiazolyl, R3 is I and R1 is Me.
373F Q3 is 2-Cl-5-thiazolyl, R3 is Me and R1 is Me.
374F Q3 is 2-Cl-5-thiazolyl, R3 is MeO and R1 is Me.
375F Q3 is 2-Cl-5-thiazolyl, R3 is MeS and R1 is Me.
376F Q3 is 2-Cl-5-thiazolyl, R3 is Et and R1 is Me.
377F Q3 is 2-Cl-5-thiazolyl, R3 is Me and R1 is Et.
378F Q3 is 2-Cl-5-thiazolyl, R3 is Cl and R1 is Et.
379F Q3 is 5-Me-3-isothiazolyl, R3 is Cl and R1 is CFH2.
380F Q3 is 5-Me-3-isothiazolyl, R3 is Br and R^ is Me.
381F Q3 is 5-Me-3-isothiazolyl, R3 is I and R^ is Me.
382F Q3 is 5-Me-3-isothiazolyl, R3 is Me and R^ is Me.
383F Q3 is 5-Me-3-isothiazolyl, R3 is MeO and R^ is Me.
384F Q3 is 5-Me-3-isothiazolyl, R3 is MeS and R^ is Me.
385F Q3 is 5-Me-3-isothiazolyl, R3 is Et and R^ is Me.
386F Q3 is 5-Me-3-isothiazolyl, R3 is Me and R^ is Et.
387F Q3 is 5-Me-3-isothiazolyl, R3 is Cl and R^ is Et.
Figure imgf000167_0001
R3 is Cl, R1 is Me and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
6-CF3 -3 -pyridinyl 5-Me-3-pyridinyl
2-Cl, 6-CF3 -3 -pyridinyl 5-F-3-pyridinyl
2-Cl, 6-MeO-3 -pyridinyl 6-Me-3 -pyridinyl
2-Cl, 6-Me-3 -pyridinyl 6-C1-3 -pyridinyl
6-MeO-3 -pyridinyl 5-Cl-3-pyridinyl
6-Br-3 -pyridinyl 6-CF3 -3 -pyridinyl
2-CF3-5-pyridinyl 2-Cl-5-pyridinyl
6-Me-3 -pyridinyl 6-C1-3 -pyridinyl
2-MeO-5-pyridinyl
Figure imgf000167_0002
The present disclosure also includes Tables IG through 23G, each of which is constructed the same as Table 7 above except that the row heading in Table 7 (i.e. "R3 is Cl, R1 is Me and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O") is replaced with the respective row heading shown below. Thus, for example, in Table IG the row heading is "R3 is Br, R1 is Me and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O", and Q3 is as defined in Table 7 above. Tables 2G through 23 G are constructed similarly.
Table Number Row Heading
IG R3 is Br, R1 is Me and (R5a)m is 2,6-di-F, 4-MeNH(CH2^O. 2G R3 is Me, R1 is Me and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O. 3G R3 is Cl, R1 is Me and (R5b)m is 2,6-di-F, 4-Me2N(CH2)3O. 4G R3 is Br, R1 is Me and (R5b)m is 2,6-di-F, 4-Me2N(CH2)3O. 5G R3 is Me, R1 is Me and (R5b)m is 2,6-di-F, 4-Me2N(CH2)3O. 6G R3 is Cl, R1 is Me and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O. 7G R3 is Br, R1 is Me and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O. 8G R3 is Me, R1 is Me and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O. 9G R3 is Cl, R1 is Me and (R5a)m is 2-C1-6-F, 4-MeNH(CH2)3O. 1OG R3 is Br, R1 is Me and (R5a)m is 2-C1-6-F, 4-MeNH(CH2)3O.
HG R3 is Me, R1 is Me and (R5a)m is 2-C1-6-F, 4-MeNH(CH2)3O.
12G R3 is Cl, R1 is Me and (R5a)m is 2,6-di-F, 3-MeNH(CH2)3O. Table Number Row Heading
13G R3 is Br5 R1 is Me and (R5a)m is 2,6-di-F, 3-MeNH(CH2)3O.
14G R3 is Me, R 1 is Me and (R5a)m is 2,6-di-F, 3-MeNH(CH2)3θ.
15G R3 is Cl5 R1 is Me and (R5a)m is 2,6-di-F, 3-Me2N(CH2)3θ.
16G R3 is Br5 R1 is Me and (R5a)m is 2,6-di-F, 3-Me2N(CH2)3O.
17G R3 is Me, R 1 is Me and (R5a)m is 2,6-di-F, 3-Me2N(CH2)3O.
18G R3 is Cl5 R1 is Me and (R5a)m is 2,6-di-F, 3-MeO(CH2)3O.
19G R3 is Br5 R1 is Me and (R5a)m is 2,6-di-F, 3-MeO(CH2)3O.
2OG R3 is Me, R 1 is Me and (R5a)m is 2,6-di-F, 3-MeO(CH2)3O.
21G R3 is Cl5 R1 is Me and (R5a)m is 2-C1-6-F, 4-MeNH(CH2)3O.
22G R3 is Br5 R1 is Me and (R5a)m is 2-C1-6-F, 3-MeNH(CH2)3O.
23G R3 is Me, R 1 is Me and (R5a)m is 2-C1-6-F, 3-MeNH(CH2)3O.
Table 8
Figure imgf000168_0002
Figure imgf000168_0001
The present disclosure also includes Tables IH through 23H, each of which is constructed the same as Table 8 above except that the row heading in Table 8 (i.e. "R3 is Cl, R1 is Me and (R5c)p is 2,6-di-F, 4-MeNH(CH2)3O") is replaced with the respective row heading shown below. Thus, for example, in Table IH the row heading is "R3 is Br, R1 is Me and (R5c)p is 2,6-di-F, 4-MeNH(CH2)3O", and Q1 is as defined in Table 8 above. Tables 2G through 23 G are constructed similarly. Table Number Row Heading
IH R3 is Br5 R1 is Me and (R5c)p is 2,6-di-F, 4-MeNH(CH2)3O.
2H R3 is Me5 R1 is Me and (R5c)p is 2,6-di-F, 4-MeNH(CH2)3θ.
3H R3 is Cl5 R1 is Me and (R5c)p is 2,6-di-F, 4-Me2N(CH2)3θ.
4H R3 is Br5 R1 is Me and (R5c)p is 2,6-di-F, 4-Me2N(CH2)3O.
5H R3 is Me5 R1 is Me and (R5c)p is 2,6-di-F, 4-Me2N(CH2)3O.
6H R3 is Cl5 R1 is Me and (R5c)p is 2,6-di-F, 4-MeO(CH2)3O.
7H R3 is Br5 R1 is Me and (R5a)p is 2,6-di-F, 4-MeO(CH2)3O.
8H R3 is Me5 R1 is Me and (R5c)p is 2,6-di-F, 4-MeO(CH2)3O.
9H R3 is Cl5 R1 is Me and (R5c)p is 2-C1-6-F, 4-MeNH(CH2)3O.
1OH R3 is Br5 R1 is Me and (R5c)p is 2-C1-6-F, 4-MeNH(CH2)3O.
HH R3 is Me5 R1 is Me and (R5c)p is 2-C1-6-F, 4-MeNH(CH2)3O.
12H R3 is Cl5 R1 is Me and (R5c)p is 2,6-di-F, 3-MeNH(CH2)3O.
13H R3 is Br5 R1 is Me and (R5c)p is 2,6-di-F, 3-MeNH(CH2)3O.
14H R3 is Me5 R1 is Me and (R5c)p is 2,6-di-F, 3-MeNH(CH2)3O.
15H R3 is Cl5 R1 is Me and (R5c)p is 2,6-di-F, 3-Me2N(CH2)3O.
16H R3 is Br5 R1 is Me and (R5c)p is 2,6-di-F, 3-Me2N(CH2)3O.
17H R3 is Me5 R1 is Me and (R5c)p is 2,6-di-F, 3-Me2N(CH2)3O.
18H R3 is Cl5 R1 is Me and (R5c)p is 2,6-di-F, 3-MeO(CH2)3O.
19H R3 is Br5 R1 is Me and (R5c)p is 2,6-di-F, 3-MeO(CH2)3O.
2OH R3 is Me5 R1 is Me and (R5c)p is 2,6-di-F, 3-MeO(CH2)3O.
21H R3 is Cl5 R1 is Me and (R5c)p is 2-C1-6-F, 4-MeNH(CH2)3O.
22H R3 is Br5 R1 is Me and (R5c)p is 2-C1-6-F, 3-MeNH(CH2)3O.
23H R3 is Me5 R1 is Me and (R5c)p is 2-C1-6-F, 3-MeNH(CH2)3O.
Table 9
Figure imgf000169_0001
Q2 is 4-Cl-Ph and R2 is Me.
Figure imgf000169_0002
Q2 is 4-Cl-Ph and R2 is Me.
(R5a}
'm
2-Cl, 4-MeO
2-Br, 4-MeO
2,6-di-F, 3-Cl
2,6-di-F, 3 -CN
2,6-di-F, 3-MeO
2,6-di-F, 4-CF2HO
2,6-di-F, 3-CF2HO
Figure imgf000170_0001
Figure imgf000170_0002
The present disclosure also includes Tables IJ through 65 J, each of which are constructed the same as Table 9 above except that the row heading in Table 9 (i.e. "Q2 is 4-Cl-Ph and R2 is Me") is replaced with the respective row headings shown below. Thus, for example, in Table IJ the row heading is "Q^ is 4-Cl-Ph and R2 is Br", and (R5a)m is as defined in Table 9 above. Tables 2J through 65 J are constructed similarly.
Table Number Row Heading
U Q2 is 4-Cl-Ph, R2 is Br.
2J Q2 is 4-Cl-Ph, R2 is Cl.
3J Q2 is 3-F-Ph, R2 is Me.
4J Q2 is 3-F-Ph, R2 is Br.
5J Q2 is 3-F-Ph, R2 is Cl.
6J Q2 is 3-OCF2H-Ph, R2 is Me.
7J Q2 is 3-CF2HO-Ph, R2 is Br.
8J Q2 is 3-CF2HO-Ph, R2 is Cl.
9J Q2 is 4-Cl, 3-F-Ph, R2 is Me.
1OJ Q2 is 4-Cl, 3-F-Ph, R2 is Br.
I U Q2 is 4-Cl, 3-F-Ph, R2 is Cl.
12J Q2 is 2-Cl, 4-F-Ph, R2 is Me.
13J Q2 is 2-Cl, 4-F-Ph, R2 is Br.
14J Q2 is 2-Cl, 4-F-Ph, R2 is Cl.
15J Q2 is 3,5-di-MeO-Ph, R2 is Me.
16J Q2 is 3,5-di-MeO-Ph, R2 is Br.
17J Q2 is 3,5-di-MeO-Ph, R2 is Cl.
18J Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Me.
19J Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Br.
2OJ Q2 is 2-Cl, 3,5-di-MeO-Ph, R2 is Cl.
21J Q2 is 4-Cl-Bn, R2 is Me.
22J Q2 is 4-Cl-Bn, R2 is Br. Table Number Row Heading
23J Q2 is 4-Cl-Bn, R2 is Cl.
24J Q2 is 6-Cl-3-pyridinyl, R2 is Me.
25J Q2 is 6-Cl-3-pyridinyl, R2 is Br.
26J Q2 is 6-Cl-3-pyridinyl, R2 is Cl.
27J Q2 is 6-MeO-3-pyridinyl, R2 is Me.
28J Q2 is 6-MeO-3-pyridinyl, R2 is Br.
29J Q2 is 6-MeO-3-pyridinyl, R2 is Cl.
3OJ Q2 is 5-F-3-pyridinyl, R2 is Me.
31J Q2 is 5-F-3-pyridinyl, Rz is Br.
32J Q2 is 5-F-3-pyridinyl, R2 is Cl.
33J Q2 is 6-Cl-3-pyridazinyl, R2 is Me.
34J Q2 is 6-Cl-3-pyridazinyl, Rz is Br.
35J Q2 is 6-Cl-3-pyridazinyl, R2 is Cl.
36J Q2 is 5-Cl-3-pyridazinyl, Rz is Me.
37J Q2 is 5-Cl-3-pyridazinyl, R2 is Br.
38J Q2 is 5-Cl-3-pyridazinyl, R2 is Cl.
39J Q2 is 2-Cl-5-pyrimidinyl, Rz is Me.
4OJ Q2 is 2-Cl-5-pyrimidinyl, R2 is Br.
41J Q2 is 2-Cl-5-pyrimidinyl, Rz is Cl.
42J Q2 is 2-Me-5-pyrimidinyl, R2 is Me.
43J Q2 is 2-Me-5-pyrimidinyl, Rz is Br.
44J Q2 is 2-Me-5-pyrimidinyl, R2 is Cl.
45J Q2 is 5-Cl-2-pyrimidinyl, Rz is Me.
46J Q2 is 5-Cl-2-pyrimidinyl, R2 is Br.
47J Q2 is 5-Cl-2-pyrimidinyl, Rz is Cl.
48J Q2 is 5-Cl-2-thienyl, R2 is Me.
49J Q2 is 5-Cl-2-thienyl, R2 is Br.
5OJ Q2 is 5-Cl-2-thienyl, R2 is Cl.
51J Q2 is 5-Me-3-thienyl, R2 is Me.
52J Q2 is 5-Me-3-thienyl, R2 is Br.
53J Q2 is 5-Me-3-thienyl, R2 is Cl.
54J Q2 is l-Me-l//-pyrazol-3-yl, Rz is Me.
55J Q2 is l-Me-l//-pyrazol-3-yl, R2 is Br.
56J Q2 is l-Me-l//-pyrazol-3-yl, R2 is Cl.
57J Q2 is l-Me-l//-pyrazol-4-yl, R2 is Me.
58J Q2 is l-Me-l//-pyrazol-4-yl, R2 is Br.
59J Q2 is l-Me-l//-pyrazol-4-yl, R2 is Cl. Table Number Row Heading
6OJ Q2 is 2-Cl-5-thiazolyl, R2 is Me
61J Q2 is 2-Cl-5-thiazolyl, R2 is Br.
62J Q2 is 2-Cl-5-thiazolyl, R2 is Cl.
63J Q2 is 5-Me-3-isothiazolyl, R2 is Me.
64J Q2 is 5-Me-3-isothiazolyl, R2 is Br.
65J Q2 is 5-Me-3-isothiazolyl, R2 is Cl.
Table 10
Figure imgf000172_0001
Q1 is 4-Cl-Ph and R2 is Me.
(R5b)n
4-CN, 2,6-di-F
2,6-di-F, 4-Me
2-Cl, 5-CF3
2-Cl, 4-Me
2-Cl, 4-MeO
2-Br, 4-MeO
2,6-di-F, 3 -Cl
2,6-di-F, 3 -CN
2,6-di-F, 3-MeO
2,6-di-F, 4-CF2HO
2,6-di-F, 3-CF2HO
Figure imgf000172_0002
Figure imgf000172_0003
The present disclosure also includes Tables IK through 65K, each of which are constructed the same as Table 10 above except that the row heading in Table 10 (i.e. "Q1 is 4-Cl-Ph and R2 is Me") is replaced with the respective row heading shown below. Thus, for example, in Table IK the row heading is "Ql is 4-Cl-Ph and R1 is Br", and (R5^)n is as defined in Table 10 above. Tables 2K through 65K are constructed similarly. Table Number Row Heading
IK Q1 is 4-Cl-Ph, R2 is Br.
2K Q1 is 4-Cl-Ph, R2 is Cl.
3K Q1 is 3-F-Ph, R2 is Me.
4K Q1 is 3-F-Ph, R2 is Br.
5K Q1 is 3-F-Ph, R2 is Cl.
6K Q1 is 3-CF2HO-Ph, R2 is Me.
7K Q1 is 3-CF2HO-Ph, R2 is Br.
8K Q1 is 3-CF2HO-Ph, R2 is Cl.
9K Q1 is 4-Cl, 3-F-Ph, R2 is Me.
1OK Q1 is 4-Cl, 3-F-Ph, R2 is Br.
HK Q1 is 4-Cl, 3-F-Ph, R2 is Cl.
12K Q1 is 2-Cl, 4-F-Ph, R2 is Me.
13K Q1 is 2-Cl, 4-F-Ph, R2 is Br.
14K Q1 is 2-Cl, 4-F-Ph, R2 is Cl.
15K Q1 is 3,5-di-MeO-Ph, R2 is Me.
16K Q1 is 3,5-di-MeO-Ph, R2 is Br.
17K Q1 is 3,5-di-MeO-Ph, R2 is Cl.
18K Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Me.
19K Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Br.
2OK Q1 is 2-Cl, 3,5-di-MeO-Ph, R2 is Cl.
21K Q1 is 4-Cl-Bn, R2 is Me.
22K Q1 is 4-Cl-Bn, R2 is Br.
23K Q1 is 4-Cl-Bn, R2 is Cl.
24K Q1 is 6-Cl-3-pyridinyl, R2 is Me.
25K Q1 is 6-Cl-3-pyridinyl, R2 is Br.
26K Q1 is 6-Cl-3-pyridinyl, R2 is Cl.
27K Q1 is 6-MeO-3-pyridinyl, R2 is Me.
28K Q1 is 6-MeO-3-pyridinyl, R2 is Br.
29K Q1 is 6-MeO-3-pyridinyl, R2 is Cl.
3OK Q1 is 5-F-3-pyridinyl, R2 is Me.
31K Q1 is 5-F-3-pyridinyl, Rz is Br.
32K Q1 is 5-F-3-pyridinyl, R2 is Cl.
33K Q1 is 6-Cl-3-pyridazinyl, R2 is Me.
34K Q1 is 6-Cl-3-pyridazinyl, Rz is Br.
35K Q1 is 6-Cl-3-pyridazinyl, R2 is Cl.
36K Q1 is 5-Cl-3-pyridazinyl, Rz is Me.
37K Q1 is 5-Cl-3-pyridazinyl, R2 is Br. Table Number Row Heading
38K Q1 is 5-Cl-3-pyridazinyl, R2 is Cl.
39K Q1 is 2-Cl-5-pyrimidinyl, R2 is Me.
4OK Q1 is 2-Cl-5-pyrimidinyl, Rz is Br.
41K Q1 is 2-Cl-5-pyrimidinyl, R2 is Cl.
42K Q1 is 2-Me-5-pyrimidinyl, Rz is Me.
43K Q1 is 2-Me-5-pyrimidinyl, R2 is Br.
44K Q1 is 2-Me-5-pyrimidinyl, Rz is Cl.
45K Q1 is 5-Cl-2-pyrimidinyl, R2 is Me.
46K Q1 is 5-Cl-2-pyrimidinyl, R2 is Br.
47K Q1 is 5-Cl-2-pyrimidinyl, R2 is Cl.
48K Q1 is 5-Cl-2-thienyl, R2 is Me.
49K Q1 is 5-Cl-2-thienyl, R2 is Br.
5OK Q1 is 5-Cl-2-thienyl, R2 is Cl.
51K Q1 is 5-Me-3-thienyl, R2 is Me.
52K Q1 is 5-Me-3-thienyl, Rz is Br.
53K Q1 is 5-Me-3-thienyl, R2 is Cl.
54K Q1 is l-Me-l//-pyrazol-3-yl, Rz is Me.
55K Q1 is l-Me-l//-pyrazol-3-yl, R2 is Br.
56K Q1 is l-Me-l//-pyrazol-3-yl, Rz is Cl.
57K Q1 is l-Me-l//-pyrazol-4-yl, R2 is Me.
58K Q1 is l-Me-l//-pyrazol-4-yl, Rz is Br.
59K Q1 is l-Me-l//-pyrazol-4-yl, R2 is Cl.
6OK Q1 is 2-Cl-5-thiazolyl, R2 is Me.
61K Q1 is 2-Cl-5-thiazolyl, R2 is Br.
62K Q1 is 2-Cl-5-thiazolyl, R2 is Cl.
63K Q1 is 5-Me-3-isothiazolyl, Rz is Me.
64K Q1 is 5-Me-3-isothiazolyl, R2 is Br.
65K Q1 is 5-Me-3-isothiazolyl, Rz is Cl.
Figure imgf000174_0001
Figure imgf000175_0001
Figure imgf000175_0002
The present disclosure also includes Tables IL through 17L, each of which are constructed the same as Table 11 above except that the row heading in Table 11 (i.e. "R2 is Cl and (R5a)m is 2,6-di-F, 4-MeNH(CH2^O.") is replaced with the respective row heading shown below. Thus, for example, in Table IL the row heading is "R2 is Br and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O", and Q2 is as define in Table 11 above. Tables 2L through 17L are constructed similarly.
Table Number Row Heading
IL R2 is Br and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
2L R2 is Me and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
3L R2 is Cl and (R5a)m is 2,6-di-F, 4-Me2N(CH2)3O.
4L R2 is Br and (R5a)m is 2,6-di-F, 4-Me2N(CH2)3O.
5L R2 is Me and (R5a)m is 2,6-di-F, 4-Me2N(CH2)3O.
6L R2 is Cl and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O.
7L R2 is Br and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O.
8L R2 is Me and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O.
9 R2 is Cl and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
1OL R2 is Br and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
HL R2 is Me and (R5a)m is 2,6-di-F, 4-MeNH(CH2)3O.
12L R2 is Cl and (R5a)m is 2,6-di-F, 4-Me2N(CH2)3O.
13L R2 is Br and (R5a)m is 2,6-di-F, 4-Me2N(CH2)3O.
14L R2 is Me and (R5a)m is 2,6-di-F, 4-Me2N(CH2)3O.
15L R2 is Cl and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O.
16L R2 is Br and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O.
17L R2 is Me and (R5a)m is 2,6-di-F, 4-MeO(CH2)3O. Table 12
Figure imgf000176_0002
6-CF3 -3 -pyridinyl 5-Me-3-pyridinyl Cl, 6-CF3 -3 -pyridinyl 5-F-3-pyridinyl Cl, 6-MeO-3 -pyridinyl 6-Me-3 -pyridinyl -Cl, 6-Me-3 -pyridinyl 6-C1-3 -pyridinyl
6-MeO-3 -pyridinyl 5-Cl-3-pyridinyl
6-Br-3 -pyridinyl 6-CF3 -3 -pyridinyl
2-CF3-5-pyridinyl 2-Cl-5-pyridinyl
6-Me-3 -pyridinyl 6-C1-3 -pyridinyl
2-MeO-5-pyridinyl
Figure imgf000176_0001
The present disclosure also includes Tables IM through 17M, each of which is constructed the same as Table 12 above except that the row heading in Table 12 (i.e. "R2 is Cl and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O.") is replaced with the respective row heading shown below. Thus, for example, in Table IM the row heading is "R2 is Br and (R5^)n is 2,6-di-F, 4-MeNH(CH2)3O", and Q2 is as defined in Table 12 above. Tables 2M through 17M are constructed similarly.
Table Number Row Heading
IM R2 is Br and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O.
2M R2 is Me and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O.
3M R2 is Cl and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3O.
4M R2 is Br and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3O.
5M R2 is Me and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3O.
6M R2 is Cl and (R5b)n is 2,6-di-F, 4-MeO(CH2)3O.
7M R2 is Br and (R5b)n is 2,6-di-F, 4-MeO(CH2)3O.
8M R2 is Me and (R5b)n is 2,6-di-F, 4-MeO(CH2)3O.
9 R2 is Cl and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O.
1OM R2 is Br and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O.
HM R2 is Me and (R5b)n is 2,6-di-F, 4-MeNH(CH2)3O. Table Number Row Heading
12M R2 is Cl and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3θ.
13M R2 is Br and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3O.
14M R2 is Me and (R5b)n is 2,6-di-F, 4-Me2N(CH2)3θ.
15M R2 is Cl and (R5b)n is 2,6-di-F, 4-MeO(CH2)3O.
16M R2 is Br and (R5b)n is 2,6-di-F, 4-MeO(CH2)3O.
17M R2 is Me and (R5b)n is 2,6-di-F, 4-MeO(CH2)3O.
Formulation/Utility
A compound of this invention will generally be used as a fungicidal active ingredient in a composition, i.e. formulation, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serve as a carrier. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.
Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifϊable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like, which optionally can be thickened into gels. The general types of aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion. The general types of nonaqueous liquid compositions are emulsifϊable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion. The general types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) and the like, which can be water-dispersible ("wettable") or water-soluble. Films and coatings formed from film- forming solutions or flowable suspensions are particularly useful for seed treatment. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated"). Encapsulation can control or delay release of the active ingredient. An emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High-strength compositions are primarily used as intermediates for further formulation. Sprayable formulations are typically extended in a suitable medium before spraying.
Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Spray volumes can range from about from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto seeds of crops and other desirable vegetation as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake.
The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.
Weight Percent
Active
Ingredient Diluent Surfactant
Water-Dispersible and Water- 0.001-90 0-99.999 0-15 soluble Granules, Tablets and Powders
Oil Dispersions, Suspensions, 1-50 40-99 0-50 Emulsions, Solutions (including Emulsifiable Concentrates)
Dusts 1-25 70-99 0-5
Granules and Pellets 0.001-95 5-99.999 0-15
High Strength Compositions 90-99 0-10 0-2
Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Liquid diluents include, for example, water, Λ/,iV-dimethylalkanamides (e.g.,
Λ/,Λ/-dimethylformamide), limonene, dimethyl sulfoxide, JV-alkylpyrrolidones (e.g., JV-methylpyrrolidinone), ethylene glycol, Methylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffϊns), alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate and isobornyl acetate, other esters such as alkylated lactate esters, dibasic esters and γ-butyrolactone, and alcohols, which can be linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol and benzyl alcohol. Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C6-C22), such as plant seed and fruit oils (e.g., oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950.
The solid and liquid compositions of the present invention often include one or more surfactants. When added to a liquid, surfactants (also known as "surface-active agents") generally modify, most often reduce, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in a surfactant molecule, surfactants can be useful as wetting agents, dispersants, emulsifϊers or defoaming agents.
Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers where the terminal blocks are prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those prepared from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylate esters such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd peg (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycols (pegs); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar-derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides. Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides such as 7V,iV-alkyltaurates; sulfonates of benzene, cumene, toluene, xylenes, and dodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalene and alkyl naphthalene; sulfonates of fractionated petroleum; sulfosuccinamates; and sulfosuccinates and their derivatives such as dialkyl sulfosuccinate salts.
Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as JV-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.
Also useful for the present compositions are mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon 's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.
Compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants). Such formulation auxiliaries and additives may control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation auxiliaries and additives include those listed in McCutcheon 's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon' s Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222. The compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water. Active ingredient slurries, with particle diameters of up to 2,000 μm can be wet milled using media mills to obtain particles with average diameters below 3 μm. Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diameters in the 2 to 10 μm range. Dusts and powders can be prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill). Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.
For further information regarding the art of formulation, see T. S. Woods, "The Formulator's Toolbox - Product Forms for Modern Agriculture" in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; Hance et al., Weed Control Handbook, 8111 Ed., Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000.
In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Tables A- C. Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be constructed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except where otherwise indicated.
Example A High Strength Concentrate
Compound 159 98.5% silica aerogel 0.5% synthetic amorphous fine silica 1.0%
Example B Wettable Powder
Compound 280 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%
Example C
Granule
Compound 2 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm; 90.0%
U.S.S. No. 25-50 sieves)
Example D
Extruded Pellet
Compound 37 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%
Example E
Emulsifiable Concentrate
Compound 122 10.0% polyoxyethylene sorbitol hexoleate 20.0%
C6-C10 fatty acid methyl ester 70.0% Example F Microemulsion
Compound 393 5.0% polyvinylpyrrolidone -vinyl acetate copolymer 30.0% alkylpolyglycoside 30.0% glyceryl monooleate 15.0% water 20.0%
Example G
Seed Treatment
Compound 2 20.00% polyvinylpyrrolidone -vinyl acetate copolymer 5.00% montan acid wax 5.00% calcium ligninsulfonate 1.00% polyoxyethylene/polyoxypropylene block copolymers 1.00% stearyl alcohol (POE 20) 2.00% polyorganosilane 0.20% colorant red dye 0.05% water 65.75%
Formulations such as those in the Formulation Table are typically diluted with water to form aqueous compositions before application. Aqueous compositions for direct applications to the plant or portion thereof (e.g., spray tank compositions) typically comprise at least about 1 ppm or more (e.g., from 1 ppm to 100 ppm) of the compound(s) of this invention.
The compounds of this invention are useful as plant disease control agents. The present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound. The compounds and/or compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, turf, vegetable, field, cereal, and fruit crops. These pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora capsici, Pythium diseases such as Pythium aphanidermatum, and diseases in the Peronosporaceae family such as Plasmopara viticola, Peronospora spp. (including Peronospora tabacina and Peronospora parasitica), Pseudoperonospora spp. (including Pseudoperonospora cubensis) and Bremia lactucae; Ascomycetes, including Alternaria diseases such as Alternaria solani and Alternaria brassicae, Guignardia diseases such as Guignardia bidwell, Venturia diseases such as Venturia inaequalis, Septoria diseases such as Septoria nodorum and Septoria tritici, powdery mildew diseases such as Erysiphe spp. (including Erysiphe graminis and Erysiphe polygonϊ), Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotricha, Pseudocercosporella herpotrichoides, Botrytis diseases such as Botrytis cinerea, Monilinia fructicola, Sclerotinia diseases such as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis viticola, Helminthosporium diseases such as Helminthosporium tritici repentis, Pyrenophora teres, anthracnose diseases such as Glomerella or Colletotrichum spp. (such as Colletotrichum graminicola and Colletotrichum orbiculare), and Gaeumannomyces graminis; Basidiomycetes, including rust diseases caused by Puccinia spp. (such as Puccinia recondita, Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis), Hemileia vastatrix and Phakopsora pachyrhizi; other pathogens including Rutstroemia floccosum (also known as Sclerontina homoeocarpa); Rhizoctonia spp. (such as Rhizoctonia solani); Fusarium diseases such as Fusarium roseum, Fusarium graminearum and Fusarium oxysporum; Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personatum, Cercospora arachidicola and Cercospora beticola; and other genera and species closely related to these pathogens. In addition to their fungicidal activity, the compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species.
Plant disease control is ordinarily accomplished by applying an effective amount of a compound of this invention either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing. The compounds can also be applied to seeds to protect the seeds and seedlings developing from the seeds. The compounds can also be applied through irrigation water to treat plants.
Rates of application for these mixtures and compositions of this invention can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than about 1 g/ha to about 5,000 g/ha of active ingredients. Seed and seedlings can normally be protected when seed is treated at a rate of from about 0.1 to about 1O g per kilogram of seed; and vegetative propagation units (e.g., cuttings and tubers) can normally be protected when propagation unit is treated at a rate of from about 0.1 to about 10 g per kilogram of propagation unit.
Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including fungicides, insecticides, nematocides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Thus the present invention also pertains to a composition comprising a fungicidally effective amount of a compound of Formula 1 and a biologically effective amount of at least one additional biologically active compound or agent and can further comprise at least one of a surfactant, a solid diluent or a liquid diluent. For mixtures of the present invention, one or more other biologically active compounds or agents can be formulated together with a compound of Formula 1, to form a premix, or one or more other biologically active compounds or agents can be formulated separately from the compound of Formula 1, and the formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession.
Of note is a composition which in addition to the compound(s) of Formula 1 include at least one fungicidal compound selected from the group consisting of the classes (1) methyl benzimidazole carbamate (MBC) fungicides; (2) dicarboximide fungicides; (3) demethylation inhibitor (DMI) fungicides; (4) phenylamide fungicides; (5) amine/morpholine fungicides; (6) phospholipid biosynthesis inhibitor fungicides; (7) carboxamide fungicides; (8) hydroxy(2-amino-)pyrimidine fungicides; (9) anilinopyrimidine fungicides; (10) JV-phenyl carbamate fungicides; (11) quinone outside inhibitor (QoI) fungicides; (12) phenylpyrrole fungicides; (13) quinoline fungicides; (14) lipid peroxidation inhibitor fungicides; (15) melanin biosynthesis inhibitors-reductase (MBI-R) fungicides; (16) melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides; (17) hydroxyanilide fungicides; (18) squalene-epoxidase inhibitor fungicides; (19) polyoxin fungicides; (20) phenylurea fungicides; (21) quinone inside inhibitor (QiI) fungicides; (22) benzamide fungicides; (23) enopyranuronic acid antibiotic fungicides; (24) hexopyranosyl antibiotic fungicides; (25) glucopyranosyl antibiotic: protein synthesis fungicides; (26) glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides; (27) cyanoacetamideoxime fungicides; (28) carbamate fungicides; (29) oxidative phosphorylation uncoupling fungicides; (30) organo tin fungicides; (31) carboxylic acid fungicides; (32) heteroaromatic fungicides; (33) phosphonate fungicides; (34) phthalamic acid fungicides; (35) benzotriazine fungicides; (36) benzene-sulfonamide fungicides; (37) pyridazinone fungicides; (38) thiophene-carboxamide fungicides; (39) pyrimidinamide fungicides; (40) carboxylic acid amide (CAA) fungicides; (41) tetracycline antibiotic fungicides; (42) thiocarbamate fungicides; (43) benzamide fungicides; (44) host plant defense induction fungicides; (45) multi-site contact activity fungicides; (46) fungicides other than classes (1) through (45); and salts of compounds of classes (1) through (46).
Further descriptions of these classes of fungicidal compounds are provided below. (1) "Methyl benzimidazole carbamate (MBC) fungicides" (Fungicide Resistance Action Committee (FRAC) code 1) inhibit mitosis by binding to β-tubulin during microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Methyl benzimidazole carbamate fungicides include benzimidazole and thiophanate fungicides. The benzimidazoles include benomyl, carbendazim, fuberidazole and thiabendazole. The thiophanates include thiophanate and thiophanate-methy 1.
(2) "Dicarboximide fungicides" (Fungicide Resistance Action Committee (FRAC) code 2) are proposed to inhibit a lipid peroxidation in fungi through interference with NADH cytochrome c reductase. Examples include chlozolinate, iprodione, procymidone and vinclozolin.
(3) "Demethylation inhibitor (DMI) fungicides" (Fungicide Resistance Action Committee (FRAC) code 3) inhibit C14-demethylase, which plays a role in sterol production. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines and pyridines. The triazoles include azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole and uniconazole. The imidazoles include clotrimazole, imazalil, oxpoconazole, prochloraz, pefurazoate and triflumizole. The pyrimidines include fenarimol and nuarimol. The piperazines include triforine. The pyridines include pyrifenox. Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides - Properties, Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258. (4) "Phenylamide fungicides" (Fungicide Resistance Action Committee (FRAC) code
4) are specific inhibitors of RNA polymerase in Oomycete fungi. Sensitive fungi exposed to these fungicides show a reduced capacity to incorporate uridine into rRNA. Growth and development in sensitive fungi is prevented by exposure to this class of fungicide. Phenylamide fungicides include acylalanine, oxazolidinone and butyro lactone fungicides. The acylalanines include benalaxyl, benalaxyl-M, furalaxyl, metalaxyl and metalaxyl-M/mefenoxam. The oxazolidinones include oxadixyl. The butyrolactones include ofurace.
(5) "Amine/morpholine fungicides" (Fungicide Resistance Action Committee (FRAC) code 5) inhibit two target sites within the sterol biosynthetic pathway, Δ8 → Δ7 isomerase and Δ14 reductase. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. Amine/morpholine fungicides (also known as non-DMI sterol biosynthesis inhibitors) include morpholine, piperidine and spiroketal-amine fungicides. The morpholines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide. The piperidines include fenpropidin and piperalin. The spiroketal-amines include spiroxamine.
(6) "Phospholipid biosynthesis inhibitor fungicides" (Fungicide Resistance Action Committee (FRAC) code 6) inhibit growth of fungi by affecting phospholipid biosynthesis.
Phospholipid biosynthesis fungicides include phophorothiolate and dithiolane fungicides. The phosphorothiolates include edifenphos, iprobenfos and pyrazophos. The dithiolanes include isoprothiolane.
(7) "Carboxamide fungicides" (Fungicide Resistance Action Committee (FRAC) code 7) inhibit Complex II (succinate dehydrogenase) fungal respiration by disrupting a key enzyme in the Krebs Cycle (TCA cycle) named succinate dehydrogenase. Inhibiting respiration prevents the fungus from making ATP, and thus inhibits growth and reproduction. Carboxamide fungicides include benzamides, furan carboxamides, oxathiin carboxamides, thiazole carboxamides, pyrazole carboxamides and pyridine carboxamides. The benzamides include benodanil, flutolanil and mepronil. The furan carboxamides include fenfuram. The oxathiin carboxamides include carboxin and oxycarboxin. The thiazole carboxamides include thifluzamide. The pyrazole carboxamides include furametpyr, penthiopyrad, bixafen, N-[I-(I S,2R)-[ 1 , 1 '-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)- 1 -methyl- lH-pyrazole-4-carboxamide and N- [2-( 1 ,3 -dimethylbutyl)phenyl] -5 -fluoro- 1,3- dimethyl-lH-pyrazole-4-carboxamide. The pyridine carboxamides include boscalid.
(8) "Ηydroxy(2-amino-)pyrimidine fungicides" (Fungicide Resistance Action Committee (FRAC) code 8) inhibit nucleic acid synthesis by interfering with adenosine deaminase. Examples include bupirimate, dimethirimol and ethirimol.
(9) "Anilinopyrimidine fungicides" (Fungicide Resistance Action Committee (FRAC) code 9) are proposed to inhibit biosynthesis of the amino acid methionine and to disrupt the secretion of hydrolytic enzymes that lyse plant cells during infection. Examples include cyprodinil, mepanipyrim and pyrimethanil.
(10) 'W-Phenyl carbamate fungicides" (Fungicide Resistance Action Committee (FRAC) code 10) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include diethofencarb.
(11) "Quinone outside inhibitor (QoI) fungicides" (Fungicide Resistance Action Committee (FRAC) code 11) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol oxidase. Oxidation of ubiquinol is blocked at the "quinone outside" (Q0) site of the cytochrome bcγ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development. Quinone outside inhibitor fungicides (also known as strobilurin fungicides) include methoxyacrylate, methoxycarbamate, oximinoacetate, oximinoacetamide, oxazolidinedione, dihydrodioxazine, imidazolinone and benzylcarbamate fungicides. The methoxyacrylates include azoxystrobin, enestroburin (SYP-Z071) and picoxystrobin. The methoxycarbamates include pyraclostrobin. The oximinoacetates include kresoxim-methyl and trifloxystrobin. The oximinoacetamides include dimoxystrobin, metominostrobin, orysastrobin, α-[methoxyimino]-iV-methyl-2-[[[ 1 -[3-(trifluoromethyl)phenyl]ethoxy]-imino]- methylj-benzeneacetamide and 2-[[[3-(2,6-dichlorophenyl)- 1 -methyl-2-propen- 1 -ylidene]- amino]oxy]methyl]-α-(methoxyimino)-Λ/-methylbenzeneacetamide. The oxazolidinediones include famoxadone. The dihydrodioxazines include fluoxastrobin. The imidazolinones include fenamidone. The benzylcarbamates include pyribencarb. (12) "Phenylpyrrole fungicides" (Fungicide Resistance Action Committee (FRAC) code 12) inhibit a MAP protein kinase associated with osmotic signal transduction in fungi. Fenpiclonil and fludioxonil are examples of this fungicide class.
(13) "Quinoline fungicides" (Fungicide Resistance Action Committee (FRAC) code 13) are proposed to inhibit signal transduction by affecting G-proteins in early cell signaling. They have been shown to interfere with germination and/or appressorium formation in fungi that cause powder mildew diseases. Quinoxyfen is an example of this class of fungicide.
(14) "Lipid peroxidation inhibitor fungicides" (Fungicide Resistance Action Committee (FRAC) code 14) are proposed to inhibit lipid peroxidation which affects membrane synthesis in fungi. Members of this class, such as etridiazole, may also affect other biological processes such as respiration and melanin biosynthesis. Lipid peroxidation fungicides include aromatic carbon and 1,2,4-thiadiazole fungicides. The aromatic carbon fungicides include biphenyl, chloroneb, dicloran, quintozene, tecnazene and tolclofos- methyl. The 1,2,4-thiadiazole fungicides include etridiazole.
(15) "Melanin biosynthesis inhibitors-reductase (MBI-R) fungicides" (Fungicide Resistance Action Committee (FRAC) code 16.1) inhibit the naphthal reduction step in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitors-reductase fungicides include isobenzofuranone, pyrroloquinolinone and triazolobenzothiazole fungicides. The isobenzofuranones include fthalide. The pyrroloquinolinones include pyroquilon. The triazolobenzothiazoles include tricyclazole. (16) "Melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides" (Fungicide
Resistance Action Committee (FRAC) code 16.2) inhibit scytalone dehydratase in melanin biosynthesis. Melanin in required for host plant infection by some fungi. Melanin biosynthesis inhibitors-dehydratase fungicides include cyclopropanecarboxamide, carboxamide and propionamide fungicides. The cyclopropanecarboxamides include carpropamid. The carboxamides include diclocymet. The propionamides include fenoxanil. (17) "Hydroxyanilide fungicides (Fungicide Resistance Action Committee (FRAC) code 17) inhibit C4-demethylase which plays a role in sterol production. Examples include fenhexamid. (18) "Squalene-epoxidase inhibitor fungicides" (Fungicide Resistance Action Committee (FRAC) code 18) inhibit squalene-epoxidase in ergosterol biosynthesis pathway. Sterols such as ergosterol are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. Squalene- epoxidase inhibitor fungicides include thiocarbamate and allylamine fungicides. The thiocarbamates include pyributicarb. The allylamines include naftifine and terbinafme.
(19) "Polyoxin fungicides" (Fungicide Resistance Action Committee (FRAC) code 19) inhibit chitin synthase. Examples include polyoxin. (20) "Phenylurea fungicides" (Fungicide Resistance Action Committee (FRAC) code
20) are proposed to affect cell division. Examples include pencycuron.
(21) "Quinone inside inhibitor (QiI) fungicides" (Fungicide Resistance Action Committee (FRAC) code 21) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol reductase. Reduction of ubiquinol is blocked at the "quinone inside" (Qj) site of the cytochrome bcγ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development. Quinone inside inhibitor fungicides include cyanoimidazole and sulfamoyltriazole fungicides. The cyanoimidazoles include cyazofamid. The sulfamoyltriazoles include amisulbrom. (22) "Benzamide fungicides" (Fungicide Resistance Action Committee (FRAC) code
22) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include zoxamide.
(23) "Enopyranuronic acid antibiotic fungicides" (Fungicide Resistance Action Committee (FRAC) code 23) inhibit growth of fungi by affecting protein biosynthesis.
Examples include blasticidin-S.
(24) "Hexopyranosyl antibiotic fungicides" (Fungicide Resistance Action Committee (FRAC) code 24) inhibit growth of fungi by affecting protein biosynthesis. Examples include kasugamycin. (25) "Glucopyranosyl antibiotic: protein synthesis fungicides" (Fungicide Resistance
Action Committee (FRAC) code 25) inhibit growth of fungi by affecting protein biosynthesis. Examples include streptomycin.
(26) "Glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides" (Fungicide Resistance Action Committee (FRAC) code 26) inhibit trehalase in inositol biosynthesis pathway. Examples include validamycin.
(27) "Cyanoacetamideoxime fungicides (Fungicide Resistance Action Committee (FRAC) code 27) include cymoxanil. (28) "Carbamate fungicides" (Fungicide Resistance Action Committee (FRAC) code 28) are considered multi-site inhibitors of fungal growth. They are proposed to interfere with the synthesis of fatty acids in cell membranes, which then disrupts cell membrane permeability. Propamacarb, propamacarb-hydrochloride, iodocarb, and prothiocarb are examples of this fungicide class.
(29) "Oxidative phosphorylation uncoupling fungicides" (Fungicide Resistance Action Committee (FRAC) code 29) inhibit fungal respiration by uncoupling oxidative phosphorylation. Inhibiting respiration prevents normal fungal growth and development. This class includes 2,6-dinitroanilines such as fluazinam, pyrimidonehydrazones such as ferimzone and dinitrophenyl crotonates such as dinocap, meptyldinocap and binapacryl.
(30) "Organo tin fungicides" (Fungicide Resistance Action Committee (FRAC) code 30) inhibit adenosine triphosphate (ATP) synthase in oxidative phosphorylation pathway. Examples include fentin acetate, fentin chloride and fentin hydroxide.
(31) "Carboxylic acid fungicides" (Fungicide Resistance Action Committee (FRAC) code 31) inhibit growth of fungi by affecting deoxyribonucleic acid (DNA) topoisomerase type II (gyrase). Examples include oxolinic acid.
(32) "Heteroaromatic fungicides" (Fungicide Resistance Action Committee (FRAC) code 32) are proposed to affect DNA/ribonucleic acid (RNA) synthesis. Heteroaromatic fungicides include isoxazole and isothiazolone fungicides. The isoxazoles include hymexazole and the isothiazolones include octhilinone.
(33) "Phosphonate fungicides" (Fungicide Resistance Action Committee (FRAC) code 33) include phosphorous acid and its various salts, including fosetyl-aluminum.
(34) "Phthalamic acid fungicides" (Fungicide Resistance Action Committee (FRAC) code 34) include teclofthalam. (35) "Benzotriazine fungicides" (Fungicide Resistance Action Committee (FRAC) code 35) include triazoxide.
(36) "Benzene-sulfonamide fungicides" (Fungicide Resistance Action Committee (FRAC) code 36) include flusulfamide.
(37) "Pyridazinone fungicides" (Fungicide Resistance Action Committee (FRAC) code 37) include diclomezine.
(38) "Thiophene-carboxamide fungicides" (Fungicide Resistance Action Committee (FRAC) code 38) are proposed to affect ATP production. Examples include silthiofam.
(39) "Pyrimidinamide fungicides" (Fungicide Resistance Action Committee (FRAC) code 39) inhibit growth of fungi by affecting phospholipid biosynthesis and include diflumetorim.
(40) "Carboxylic acid amide (CAA) fungicides" (Fungicide Resistance Action Committee (FRAC) code 40) are proposed to inhibit phospholipid biosynthesis and cell wall deposition. Inhibition of these processes prevents growth and leads to death of the target fungus. Carboxylic acid amide fungicides include cinnamic acid amide, valinamide carbamate and mandelic acid amide fungicides. The cinnamic acid amides include dimethomorph and flumorph. The valinamide carbamates include benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb and valiphenal. The mandelic acid amides include mandipropamid, JV-[2-[4-[[3-(4-chlorophenyl)-2-propyn- 1 -yl]oxy]-3-methoxyphenyl]ethyl]- 3 -methyl-2- [(methylsulfonyl)amino]butanamide and N-[2- [4- [ [3 -(4-chlorophenyl)-2-propyn- 1 -yl]oxy] -3 -methoxyphenyl] ethyl] -3 -methyl-2- [(ethylsulfonyl)amino]butanamide .
(41) "Tetracycline antibiotic fungicides" (Fungicide Resistance Action Committee (FRAC) code 41) inhibit growth of fungi by affecting complex 1 nicotinamide adenine dinucleotide (NADH) oxidoreductase. Examples include oxytetracycline.
(42) "Thiocarbamate fungicides (b42)" (Fungicide Resistance Action Committee (FRAC) code 42) include methasulfocarb.
(43) "Benzamide fungicides" (Fungicide Resistance Action Committee (FRAC) code 43) inhibit growth of fungi by derealization of spectrin-like proteins. Examples include acylpicolide fungicides such as fluopicolide and fluopyram.
(44) "Host plant defense induction fungicides" (Fungicide Resistance Action Committee (FRAC) code P) induce host plant defense mechanisms. Host plant defense induction fungicides include benzo-thiadiazole, benzisothiazole and thiadiazole-carboxamide fungicides. The benzo-thiadiazoles include acibenzolar-S-methyl. The benzisothiazoles include probenazole. The thiadiazole-carboxamides include tiadinil and isotianil.
(45) "Multi-site contact fungicides" inhibit fungal growth through multiple sites of action and have contact/preventive activity. This class of fungicides includes: (45.1) "copper fungicides" (Fungicide Resistance Action Committee (FRAC) code Ml)", (45.2) "sulfur fungicides" (Fungicide Resistance Action Committee (FRAC) code M2), (45.3) "dithiocarbamate fungicides" (Fungicide Resistance Action Committee (FRAC) code M3), (45.4) "phthalimide fungicides" (Fungicide Resistance Action Committee (FRAC) code M4), (45.5) "chloronitrile fungicides" (Fungicide Resistance Action Committee (FRAC) code M5), (45.6) "sulfamide fungicides" (Fungicide Resistance Action Committee (FRAC) code M6), (45.7) "guanidine fungicides" (Fungicide Resistance Action Committee (FRAC) code M7), (45.8) "triazine fungicides" (Fungicide Resistance Action Committee (FRAC) code M8) and (45.9) "quinone fungicides" (Fungicide Resistance Action Committee (FRAC) code M9). "Copper fungicides" are inorganic compounds containing copper, typically in the copper(II) oxidation state; examples include copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate). "Sulfur fungicides" are inorganic chemicals containing rings or chains of sulfur atoms; examples include elemental sulfur. "Dithiocarbamate fungicides" contain a dithiocarbamate molecular moiety; examples include mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb and ziram. "Phthalimide fungicides" contain a phthalimide molecular moiety; examples include folpet, captan and captafol. "Chloronitrile fungicides" contain an aromatic ring substituted with chloro and cyano; examples include chlorothalonil. "Sulfamide fungicides" include dichlofluanid and tolyfluanid. "Guanidine fungicides" include dodine, guazatine, iminoctadine albesilate and iminoctadine triacetate. "Triazine fungicides" include anilazine. "Quinone fungicides" include dithianon.
(46) "Fungicides other than fungicides of classes (1) through (45)" include certain fungicides whose mode of action may be unknown. These include: (46.1) "thiazole carboxamide fungicides" (Fungicide Resistance Action Committee (FRAC) code U5), (46.2) "phenyl-acetamide fungicides" (Fungicide Resistance Action Committee (FRAC) code U6), (46.3) "quinazolinone fungicides" (Fungicide Resistance Action Committee (FRAC) code U7) and (46.4) "benzophenone fungicides" (Fungicide Resistance Action Committee (FRAC) code U8). The thiazole carboxamides include ethaboxam. The phenyl-acetamides include cyflufenamid and Λ/-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3- difluorophenyl]-methylene]benzeneacetamide. The quinazolinones include proquinazid and 2-butoxy-6-iodo-3-propyl-4H-l-benzopyran-4-one. The benzophenones include metrafenone. The (b46) class also includes bethoxazin, neo-asozin (ferric methanearsonate), pyrrolnitrin, quinomethionate, Λ/-[2-[4-[[3-(4-chlorophenyl)-2-propyn-l-yl]oxy]-3-methoxy- phenyl] ethyl]-3 -methyl-2- [(methylsulfonyl)amino]butanamide, N-[2- [4- [ [3 -(4-chloro- phenyl)-2-propyn- 1 -yl]oxy] -3 -methoxyphenyl] ethyl] -3 -methyl-2-[(ethyl-sulfonyl)amino] - butanamide, 2- [ [2-fluoro-5 -(trifluoromethyl)phenyl]thio] -2- [3 -(2-methoxyphenyl)-2-thiazo- lidinylidene]acetonitrile, 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine,
4-fluoro-phenyl N-[ 1 -[[[ 1 -(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate, 5- chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin-l -yl)[ 1 ,2,4]triazolo[ 1 ,5-α]pyrimidine, Λ/-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide, N-[[(cyclopropyl- methoxy)amino] [6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, Λ/1- [4-[4-chloro-3-(trifluoro-methyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-Λ/-methyl- methanimid-amide, 1 -[(2-propenylthio)carbonyl]-2-(l -methylethyl)-4-(2-methylphenyl)-5- amino-lH-pyrazol-3-one, 3-(difluoromethyl)- 1 -methyl-JV-(3',4',5'-trifluoro[ 1 , 1 '-biphenyl]-2- yl)-lH-pyrazole-4-carboxamide, 5-ethyl-6-octyl-[l,2,4]triazole[l,5-a]pyrimidin-7-amine and Initium®.
Therefore of note is a mixture (i.e. composition) comprising a compound(s) of Formula 1 and at least one fungicidal compound selected from the group consisting of the aforedescribed classes (1) through (46). Examples include compositions comprising at least one fungicidal compound selected from aforedescribed class (18), compositions comprising at least one fungicidal compound selected from aforedescribed class (19), compositions comprising at least one fungicidal compound selected from aforedescribed class (21), compositions comprising at least one fungicidal compound selected from aforedescribed class (25), compositions comprising at least one fungicidal compound selected from aforedescribed class (31), compositions comprising at least one fungicidal compound selected from aforedescribed class (34), compositions comprising at least one fungicidal compound selected from aforedescribed class (38), compositions comprising at least one fungicidal compound selected from aforedescribed class (39), compositions comprising at least one fungicidal compound selected from aforedescribed class (41), compositions comprising at least one fungicidal compound selected from aforedescribed class (45.7) and compositions comprising at least one fungicidal compound selected from aforedescribed class (45.9); including but not limited to such compositions comprising a compound(s) of Formula 1 wherein J is Q2, X is CR2, Y is N and Z is CR4, Q2 is an optionally substituted phenyl ring, an optionally substituted naphthalenyl ring system, an optionally substituted fully unsaturated heterocyclic ring, or an optionally substituted heteroaromatic bicyclic ring system, R2 is halogen and Ql is a phenyl ring or a 2-pyridinyl ring substituted with halogen at an ortho position; and such compositions comprising a compound(s) of Formula 1 wherein J is Q2, X is CR2, Y is N and Z is CR4, Q1 is an optionally substituted phenyl ring, an optionally substituted naphthalenyl ring system, an optionally substituted fully unsaturated heterocyclic ring, or an optionally substituted heteroaromatic bicyclic ring system, R4 is halogen and Q2 is a phenyl ring or a 2-pyridinyl ring substituted with halogen at an ortho position.
Also of note is a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Of particular note is a mixture (i.e. composition) comprising a compound(s) of Formula 1 and at least one fungicidal compound selected from the group of specific compounds listed above in connection with classes (1) through (46). Also of particular note is a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional surfactant selected from the group consisting of surfactants, solid diluents and liquid diluents.
Of particular note are compositions which in addition to compound(s) of Formula 1 include at least one compound selected from the group consisting of (1) alkylenebis(dithiocarbamate) fungicides; (2) cymoxanil; (3) phenylamide fungicides; (4) pyrimidinone fungicides; (5) chlorothalonil; (6) carboxamides acting at complex II of the fungal mitochondrial respiratory electron transfer site; (7) quinoxyfen; (8) metrafenone; (9) cyflufenamid; (10) cyprodinil; (11) copper compounds; (12) phthalimide fungicides; (13) fosetyl-aluminum; (14) benzimidazole fungicides; (15) cyazofamid; (16) fluazinam; (17) iprovalicarb; (18) propamocarb; (19) validomycin; (20) dichlorophenyl dicarboximide fungicides; (21) zoxamide; (22) fluopicolide; (23) mandipropamid; (24) carboxylic acid amides acting on phospholipid biosynthesis and cell wall deposition; (25) dimethomorph; (26) non-DMI sterol biosynthesis inhibitors; (27) inhibitors of demethylase in sterol biosynthesis; (28) bcγ complex fungicides; and salts of compounds of (1) through (28). Further descriptions of classes of fungicidal compounds are provided below. Pyrimidinone fungicides (group (4)) include compounds of Formula Al
Figure imgf000194_0001
Al wherein M forms a fused phenyl, thiophene or pyridine ring; R11 is C1-C6 alkyl; R12 is C1 C6 alkyl or C1-C6 alkoxy; R13 is halogen; and R14 is hydrogen or halogen.
Pyrimidinone fungicides are described in PCT Patent Application Publication WO 94/26722 and U.S. Patents 6,066,638, 6,245,770, 6,262,058 and 6,277,858. Of note are pyrimidinone fungicides selected from the group: 6-bromo-3-propyl-2-propyloxy-4(3H)- quinazolinone, 6,8-diiodo-3-propyl-2-propyloxy-4(3H)-quinazolinone, 6-iodo-3-propyl- 2-propyloxy-4(3H)-quinazolinone (proquinazid), 6-chloro-2-propoxy-3-propyl-thieno-[2,3- J]pyrimidin-4(3H)-one, 6-bromo-2-propoxy-3-propylthieno[2,3-J]pyrimidin-4(3H)-one, 7- bromo-2-propoxy-3-propylthieno[3,2-d]pyrimidin-4(3H)-one, 6-bromo-2-propoxy-3- propylpyrido[2,3-J]pyrimidin-4(3H)-one, 6,7-dibromo-2-propoxy-3-propyl-thieno-[3,2- <i]pyrimidin-4(3H)-one, and 3-(cyclopropylmethyl)-6-iodo-2-(propyl-thio)-pyrido-[2,3- J]pyrimidin-4(3H)-one.
Sterol biosynthesis inhibitors (group (27)) control fungi by inhibiting enzymes in the sterol biosynthesis pathway. Demethylase-inhibiting fungicides have a common site of action within the fungal sterol biosynthesis pathway, involving inhibition of demethylation at position 14 of lanosterol or 24-methylene dihydrolanosterol, which are precursors to sterols in fungi. Compounds acting at this site are often referred to as demethylase inhibitors, DMI fungicides, or DMIs. The demethylase enzyme is sometimes referred to by other names in the biochemical literature, including cytochrome P-450 (14DM). The demethylase enzyme is described in, for example, J. Biol. Chem. 1992, 267, 13175-79 and references cited therein. DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines and pyridines. The triazoles include azaconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole and uniconazole. The imidazoles include clotrimazole, econazole, imazalil, isoconazole, miconazole, oxpoconazole, prochloraz and triflumizole. The pyrimidines include fenarimol, nuarimol and triarimol. The piperazines include triforine. The pyridines include buthiobate and pyrifenox. Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides - Properties, Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258. bcγ Complex Fungicides (group (28)) have a fungicidal mode of action which inhibits the be i complex in the mitochondrial respiration chain. The bcγ complex is sometimes referred to by other names in the biochemical literature, including complex III of the electron transfer chain, and ubihydroquinone: cytochrome c oxidoreductase. This complex is uniquely identified by Enzyme Commission number EC 1.10.2.2. The bcγ complex is described in, for example, J. Biol. Chem. 1989, 264, 14543-48; Methods Enzymol. 1986, 126, 253-71; and references cited therein. Strobilurin fungicides such as azoxystrobin, dimoxystrobin, enestroburin (SYP-Z071), fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin and trifloxystrobin are known to have this mode of action (H. Sauter et al., Angew. Chem. Int. Ed. 1999, 38, 1328-1349). Other fungicidal compounds that inhibit the bcγ complex in the mitochondrial respiration chain include famoxadone and fenamidone.
Alkylenebis(dithiocarbamate)s (group (I)) include compounds such as mancozeb, maneb, propineb and zineb. Phenylamides (group (3)) include compounds such as metalaxyl, benalaxyl, furalaxyl and oxadixyl. Carboxamides (group (6)) include compounds such as boscalid, carboxin, fenfuram, flutolanil, furametpyr, mepronil, oxycarboxin, thifluzamide, penthiopyrad and Λ/-[2-(l,3-dimethylbutyl)phenyl]-5-fluoro-l,3-dimethyl-lH- pyrazole-4-carboxamide (PCT Patent Publication WO 2003/010149), and are known to inhibit mitochondrial function by disrupting complex II (succinate dehydrogenase) in the respiratory electron transport chain. Copper compounds (group (H)) include compounds such as copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate). Phthalimides (group (12)) include compounds such as folpet and captan. Benzimidazole fungicides (group (14)) include benomyl and carbendazim. Dichlorophenyl dicarboximide fungicides (group (20)) include chlozolinate, dichlozoline, iprodione, isovaledione, myclozolin, procymidone and vinclozolin.
Non-DMI sterol biosynthesis inhibitors (group (26)) include morpholine and piperidine fungicides. The morpholines and piperidines are sterol biosynthesis inhibitors that have been shown to inhibit steps in the sterol biosynthesis pathway at a point later than the inhibitions achieved by the DMI sterol biosynthesis (group (27)). The morpholines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide. The piperidines include fenpropidin
Of further note are combinations of compound(s) of Formula 1 with azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, carbendazim, chlorothalonil, quinoxyfen, metrafenone, cyflufenamid, fenpropidine, fenpropimorph, bromuconazole, cyproconazole, difenoconazole, epoxiconazole, fenbuconazole, flusilazole, hexaconazole, ipconazole, metconazole, penconazole, propiconazole, proquinazid, prothioconazole, tebuconazole, triticonazole, famoxadone, prochloraz, penthiopyrad and boscalid (nicobifen).
Preferred for better control of plant diseases caused by fungal plant pathogens (e.g., lower use rate or broader spectrum of plant pathogens controlled) or resistance management are mixtures of a compound of this invention with a fungicide selected from the group: azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, quinoxyfen, metrafenone, cyflufenamid, fenpropidine, fenpropimorph, cyproconazole, epoxiconazole, flusilazole, metconazole, propiconazole, proquinazid, prothioconazole, tebuconazole, triticonazole, famoxadone and penthiopyrad.
In certain instances, combinations of a compound of this invention with other biologically active (particularly fungicidal) compounds or agents (i.e. active ingredients) can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective control is always desirable. When synergism of fungicidal active ingredients occurs at application rates giving agronomically satisfactory levels of fungal control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.
Of note is a combination of a compound(s) of Formula 1 with at least one other fungicidal active ingredient. Of particular note is such a combination where the other fungicidal active ingredient has different site of action from the compound(s) of Formula 1. In certain instances, a combination with at least one other fungicidal active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management. Thus, a composition of the present invention can further comprise a biologically effective amount of at least one additional fungicidal active ingredient having a similar spectrum of control but a different site of action.
When one or more of these various mixing partners are used, the weight ratio of these various mixing partners (in total) to the compound(s) of Formula 1 is typically between about 1 :3000 and about 3000:1. Of note are weight ratios between about 1 :300 and about 300:1 (for example ratios between about 1 :30 and about 30:1). One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity. It will be evident that including these additional components may expand the spectrum of diseases controlled beyond the spectrum controlled by the compound of Formula 1 alone.
Specific weight ratios illustrative of the mixtures, compositions and methods of the present invention are listed in Table Al. The first column of Table Al lists the specific mixing partner compound (e.g., "Acibenzolar-S-methyl" in the first line). The second, third and fourth columns of Table Al lists ranges of weight ratios for rates at which the mixing partner compound is typically applied relative to a compound(s) of Formula 1. Thus, for example, the first line of Table Al specifically discloses the combination of a compound(s) of Formula 1 with acibenzolar-S-methyl is typically applied in a weight ratio between 1 :4 to 210:1. The remaining lines of Table Al are to be construed similarly.
Table Al
Figure imgf000197_0001
Figure imgf000198_0001
Figure imgf000199_0001
Figure imgf000200_0001
Figure imgf000201_0001
Figure imgf000202_0001
Figure imgf000203_0001
Examples of insecticides with which compounds of this invention can be formulated are: abamectin, acephate, acetamiprid, amidoflumet (S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, 3-bromo-l-(3-chloro-2-pyridinyl)-Λ/-[4-cyano-2- methyl-6-[(methylamino)carbonyl]phenyl]-lH-pyrazole-5-carboxamide, buprofezin, carbofuran, cartap, chlorantraniliprole (DPX-E2Y45), chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dieldrin, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fϊpronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim (UR-50701), flufenoxuron, fonophos, halofenozide, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, metofluthrin, monocrotophos, methoxyfenozide, nitenpyram, nithiazine, novaluron, noviflumuron (XDE-007), oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, pymetrozine, pyrafluprole, pyrethrin, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen (BSN 2060), spirotetramat, sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, trichlorfon and triflumuron; and biological agents including entomopathogenic bacteria, such as Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, and the encapsulated delta-endotoxins of Bacillus thuringiensis (e.g., Cellcap, MPV, MPVII); entomopathogenic fungi, such as green muscardine fungus; and entomopathogenic virus including baculovirus, nucleopolyhedro virus (NPV) such as HzNPV, AfNPV; and granulosis virus (GV) such as CpGV.
Table A2 lists specific combinations of invertebrate pest control agents with a compound(s) of Formula 1 illustrative of mixtures and compositions comprising these active ingredients and methods using them according to the present invention. The first column of Table A2 lists the specific invertebrate pest control agents (e.g., "Abamectin" in the first line). The second column of Table A2 lists the mode of action (if known) or chemical class of the invertebrate pest control agents. The third column of Table A2 lists embodiment(s) of ranges of weight ratios for rates at which the invertebrate pest control agent is typically applied relative to a compound(s) of Formula 1. Thus, for example, the first line of Table A2 specifically discloses the combination of a compound(s) of Formula 1 with abamectin is typically applied in a weight ratio between 50:1 to 1 :50. The remaining lines of Table A2 are to be construed similarly.
Table A2
Figure imgf000204_0001
Figure imgf000205_0001
Figure imgf000206_0001
One embodiment of invertebrate pest control agents (e.g., insecticides and acaricides) for mixing with a compound(s) of Formula 1 include sodium channel modulators such as bifenthrin, cypermethrin, cyhalothrin, lambda-cyhalothrin, cyfluthrin, beta-cyfluthrin, deltamethrin, dimefluthrin, esfenvalerate, fenvalerate, indoxacarb, metofluthrin, profluthrin, pyrethrin and tralomethrin; cholinesterase inhibitors such as chlorpyrifos, methomyl, oxamyl, thiodicarb and triazamate; neonicotinoids such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam; insecticidal macrocyclic lactones such as spinetoram, spinosad, abamectin, avermectin and emamectin; GABA (γ-aminobutyric acid)-regulated chloride channel blockers such as endosulfan, ethiprole and fϊpronil; chitin synthesis inhibitors such as buprofezin, cyromazine, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron and triflumuron; juvenile hormone mimics such as diofenolan, fenoxycarb, methoprene and pyriproxyfen; octopamine receptor ligands such as amitraz; ecdysone agonists such as azadirachtin, methoxyfenozide and tebufenozide; ryanodine receptor ligands such as ryanodine, anthranilic diamides such as chlorantraniliprole (see U.S. Patent 6,747,047, PCT Publications WO 2003/015518 and WO 2004/067528), flubendiamide (see U.S. Patent 6,603,044), 3-bromo-l-(3-chloro-2- pyridinyl)-Λ/-[4-cyano-2-methyl-6-[[(l-methylethyl)amino]carbonyl]phenyl]-lH-pyrazole-5- carboxamide, 3-bromo-l-(3-chloro-2-pyridinyl)-Λ/-[4-cyano-2-methyl-6-
[(methylamino)carbonyl]phenyl]-lH-pyrazole-5-carboxamide, 3-chloro-l-(3-chloro-2- pyridinyl)-Λ/-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]- lH-pyrazole-5- carboxamide and 3-chloro- 1 -(3-chloro-2-pyridinyl)-Λ/-[4-cyano-2-methyl-6-[[(l - methylethyl)amino]carbonyl]phenyl]-lH-pyrazole-5-carboxamide; nereistoxin analogs such as cartap; mitochondrial electron transport inhibitors such as chlorfenapyr, hydramethylnon and pyridaben; lipid biosynthesis inhibitors such as spirodiclofen and spiromesifen; cyclodiene insecticides such as dieldrin; cyflumetofen; fenothiocarb; flonicamid; metaflumizone; pyrafluprole; pyridalyl; pyriprole; pymetrozine; spirotetramat; and thiosultap-sodium. One embodiment of biological agents for mixing with a compound(s) Formula 1 include nucleopolyhedro virus such as HzNPV and AfNPV; Bacillus thuringiensis and encapsulated delta-endotoxins of Bacillus thuringiensis such as Cellcap, MPV and MPVII; as well as naturally occurring and genetically modified viral insecticides including members of the family Baculoviridae as well as entomophagous fungi. Of note is a composition comprising a compound of Formula 1 and at least one additional biologically active compound or agent selected from the Invertebrate Pest Control Agents listed in Table A2 above. Compounds of this invention and compositions thereof can be applied to plants genetically transformed to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins). The effect of the exogenously applied fungicidal compounds of this invention may be synergistic with the expressed toxin proteins.
General references for these agricultural protectants (i.e. insecticides, fungicides, nematocides, acaricides, herbicides and biological agents) include The Pesticide Manual, 13th Edition, C. D. S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2003 and The BioPesticide Manual, 2nd Edition, L. G. Copping, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2001. Compounds of this invention and mixtures with one or more other biologically active compounds provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, foliar pathogens of crops including: cereal grain crops such as wheat, barley, oats, rye, triticale, rice, maize, sorghum and millet; vine crops such as table and wine grapes; field crops such as oilseed rape (canola), sunflower; sugar beets, sugar cane, soybean, peanuts (groundnut), tobacco, alfafa, clover, lespedeza, trefoil and vetch; pome fruits such as apple, pear, crabapple, loquat, mayhaw and quince; stone fruits such as peaches, cherries, plums, apricots, nectarines and almonds; citrus fruits such as lemons, limes, oranges, grapefruit, mandarin (tangerines) and kumquat; root and tuber vegetables and field crops (and their foliage) such as artichoke, garden and sugar beet, carrot, cassava, ginger, ginseng, horseradish, parsnip, potato, radish, rutabaga, sweet potato, turnip and yam; bulb vegetables such as garlic, leek, onion and shallot; leafy vegetables such as arugula (roquette), celery, celery, cress, endive (escarole), fennel, head and leaf lettuce, parsley, radicchio (red chicory), rhubarb, spinach and Swiss chard; brassica (cole) leafy vegetables such as broccoli, broccoli raab (rapini), Brussels sprouts, cabbage, bok choy, cauliflower, collards, kale, kohlrabi, mustard and greens; legume vegetables (succulent or dried) such as lupin, bean (Phaseolus spp.) (including field bean, kidney bean, lima bean, navy bean, pinto bean, runner bean, snap bean, tepary bean and wax bean), bean (Vigna spp.) (including adzuki bean, asparagus bean, blackeyed pea, catjang, Chinese longbean, cowpea, crowder pea, moth bean, mung bean, rice bean, southern pea, urd bean and yardlong bean), broad bean (fava), chickpea (garbanzo), guar, jackbean, lablab bean, lentil and pea (Pisum spp.) (including dwarf pea, edible -podded pea, English pea, field pea, garden pea, green pea, snowpea, sugar snap pea, pigeon pea and soybean); fruiting vegetables such as eggplant, groundcherry (Physalis spp.), pepino and pepper (including bell pepper, chili pepper, cooking pepper, pimento, sweet pepper; tomatillo and tomato); cucurbit vegetables such as Chayote (fruit), Chinese waxgourd (Chinese preserving melon), citron melon, cucumber, gherkin, edible gourd (including hyotan, cucuzza, hechima, and Chinese okra), Momordica spp. (including balsam apple, balsam pear, bittermelon and Chinese cucumber), muskmelon (including cantaloupe and pumpkin), summer and winter squash (including butternut squash, calabaza, hubbard squash, acorn squash, spaghetti squash) and watermelon; berries such as blackberry (including bingleberry, boysenberry, dewberry, lowberry, marionberry, olallieberry and youngberry), blueberry, cranberry, currant, elderberry, gooseberry, huckleberry, loganberry, raspberry and strawberry; tree nuts such as almond, beech nut, Brazil nut, butternut, cashew, chestnut, chinquapin, filbert (hazelnut), hickory nut, macadamia nut, pecan and walnut; tropical fruits and other crops such as bananas, plantains, mangos, coconuts, papaya, guava, avocado, lichee, agave, coffee, cacao, sugar cane, oil palm, sesame, rubber and spices; fiber crops such as cotton, flax and hemp; turfgrasses (including warm- and cool-season turfgrasses) such as bentgrass, Kentucky bluegrass, St. Augustine grass, tall fescue and Bermuda grass.
These pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora capsici, Pythium diseases such as Pythium aphanidermatum, and diseases in the Peronosporaceae family such as Plasmopara viticola, Peronospora spp. (including Peronospora tabacina and Peronospora parasitica), Pseudoperonospora spp. (including Pseudoperonospora cubensis) and Bremia lactucae; Ascomycetes, including Alternaria diseases such as Alternaria solani and Alternaria brassicae, Guignardia diseases such as Guignardia bidwelli, Venturia diseases such as Venturia inaequalis, Septoria diseases such as Septoria nodorum and Septoria tritici, powdery mildew diseases such as Erysiphe spp. (including Erysiphe graminis and Erysiphe polygonϊ), Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotricha, Pseudocercosporella herpotrichoides, Botrytis diseases such as Botrytis cinerea, Monilinia fructicola, Sclerotinia diseases such as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis viticola, Helminthosporium diseases such as Helminthosporium tritici repentis, Pyrenophora teres, anthracnose diseases such as Glomerella or Colletotrichum spp. (such as Colletotrichum graminicola and Colletotrichum orbiculare), and Gaeumannomyces graminis; Basidiomycetes, including rust diseases caused by Puccinia spp. (such as Puccinia recondita, Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis), Hemileia vastatrix and Phakopsora pachyrhizi; other pathogens including Rhizoctonia spp. (such as Rhizoctonia solani and Rhizoctonia oryzae); Fusarium diseases such as Fusarium roseum, Fusarium graminearum and Fusarium oxysporum; Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personatum, Cercospora arachidicola and Cercospora beticola; Rutstroemia floccosum (also known as Sclerontina homoeocarpd); and other genera and species closely related to these pathogens. In addition to their fungicidal activity, the compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species.
Mixtures of fungicides may provide significantly better disease control than could be predicted based on the activity of the individual components. This synergism has been described as "the cooperative action of two components of a mixture, such that the total effect is greater or more prolonged than the sum of the effects of the two (or more) taken independently" (see Tames, P. M. L., Neth. J. Plant Pathology, (1964), 70, 73-80).
Specifically preferred mixtures (compound numbers refer to compounds in Index Tables A-C) are selected from the group: combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with azoxystrobin, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with kresoxim-methyl, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with trifloxystrobin, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with picoxystrobin, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with metominostrobin/fenominostrobin, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with quinoxyfen, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with metrafenone, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with fenpropidine, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with fenpropimorph, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with cyproconazole, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with epoxiconazole, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with flusilazole, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with metconazole, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with propiconazole, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with proquinazid, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with prothioconazole, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with tebuconazole, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with triticonazole, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with famoxadone, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with penthiopyrad, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with 3 -(difluoromethyl)-l -methyl- JV- (3',4',5'-trifluoro[ 1 , 1 '-biphenyl]-2-yl)- lH-pyrazole-4-carboxamide, combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with 5-ethyl-6-octyl-[l,2,4]triazole[l,5-a]pyrimidin-7-amine, and combinations of Compound 2, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 37, Compound 122, Compound 159, Compound 205, Compound 280, Compound 393, Compound 406, Compound 430, Compound 499, Compound 500, Compound 553 with Initium®.
The following TESTS demonstrate the control efficacy of compounds of this invention on specific pathogens. The pathogen control protection afforded by the compounds is not limited, however, to these species. See Index Tables A-C for compound descriptions. See Index Table D for 1 H NMR data. The following abbreviations are used in the Index Tables which follow: i means iso, Me is methyl, Et is ethyl, Ph is phenyl, Bn is benzyl, MeO is methoxy, EtO is ethoxy, MeS is methylthio and CN is cyano. In the Index Tables when an instance of Q1, Q2 and Q3 comprises a phenyl ring attached through the linker CR7aR7b to the remained of Formula 1, locant numbers of the ring are relative to the connection of the ring to the linker CR7aR7b. The abbreviation "Cmpd." stands for "Compound", and the abbreviation "Ex." stands for "Example" and is followed by a number indicating in which example the compound is prepared. The abbreviation "m.p." stands for melting point. In Index Tables A-C the numerical value reported in the column "AP+ (M+ 1)", is the molecular weight of the observed molecular ion formed by addition of H+ (molecular weight of 1) to the molecule having the greatest isotopic abundance (i.e. M). The presence of molecular ions containing one or more higher atomic weight isotopes of lower abundance (e.g., 37C, 81C) is not reported. The reported M+l peaks were observed by mass spectrometry using atmospheric pressure chemical ionization (AP+).
INDEX TABLE A
Figure imgf000212_0001
m.p. AP+
Cmpd. Q1 Q2 R2 R4 (0C) (M+l) (Ex. 1) 2,4,6-tri-F-Ph 4-Cl-Ph Cl H *** (Ex. 5) 2,6-di-F-Ph 4-Cl-Ph Cl Me *** (Ex. 3) 2,6-di-F-Ph 4-Cl-Ph Cl Cl *** (Ex. 7) 4-F-Ph 4-Cl-Ph H Me *** (Ex. 8) 4-F-Ph 4-Cl-Ph Cl Me *** (Ex. 2) 2,4,6-tri-F-Ph 4-Cl-Ph Cl Cl ***
7 4-Cl-Ph 2-Cl, 4-F-Ph Cl Cl 129-131
9 2,6-di-F-Ph Ph Cl H 291
10 2,6-di-F-Ph Ph Cl Br 371 m.p. AT ,+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
11 2,4,6-tri-F-Ph 4-Cl-Ph Cl Br 139-141
12 2,4,6-tri-F-Ph 4-Cl-Ph Cl Me 148-150
13 2,6-di-F-Ph Ph Cl I 417
14 2,6-di-F-Ph 3-F-Ph Cl H 112-116
15 2,6-di-F-Ph Ph Cl Me 305
16 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Me2N H 382
17 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Cl H 373
18 2,4,6-tri-F-Ph 4-Cl, 3-F-Ph Cl H 114-117
19 2,6-di-F-Ph 3-F-Ph Cl Cl 131-134
20 2,4,6-tri-F-Ph 4-Cl-Ph Br H 68-70
21 2,4,6-tri-F-Ph 4-Cl-Ph Br Br 145-148
22 2,6-di-F-Ph 3-F-Ph Cl Br 120-122
23 2,4,6-tri-F-Ph 4-Cl, 3-F-Ph Cl Br 135-137
27 2,4,6-tri-F-Ph 4-Cl, 3-F-Ph Cl Cl 397
28 2,6-di-F-Ph 3-F-Ph Cl Me 323
29 2,4,6-tri-F-Ph 4-Cl, 3-F-Ph Cl Me 375
32 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Cl Br ** ** a 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Br H 417
34 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Cl Me 387
35 2,6-di-F-Ph 4-Cl-Ph Cl Br 124-126
36 2,4,6-tri-F-Ph 4-Cl, 3-F-Ph Br Br 144-146
37 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Cl Me 146-148
38 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Br H 128-130
39 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Cl H 124-127
40 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Cl Br 152-153
41 2,4,6-tri-F-Ph 4-Cl, 3-F-Ph Me Me 355
42 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Br Br 166-168
43 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Br Br 495
44 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Me Me 367
45 2,4,6-tri-F-Ph 4-Cl-Ph Me Me ** **
46 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Me H 353 (Ex. 19) 2,6-di-F-Ph 3-F-Ph Cl CH≡C 333
48 2,3,6-tri-F-Ph 4-Cl-Ph Cl Me 357
49 2-Cl, 4-F-Ph 4-Cl-Ph Cl Me 357
50 2,3,6-tri-F-Ph 4-Cl-Ph Cl Br 124-127
51 2-Cl, 4-F-Ph 4-Cl-Ph Cl Br 117-120 m.p. AT ,+
Cmpd. Q1 Q2 R2 R4
(0C) (M+ 1)
52 2-Cl, 6-F-Ph 4-Cl-Ph Cl Br 174-177
53 2-Cl, 6-F-Ph 4-Cl-Ph Cl Me 357
54 2,6-di-F-Ph 3,5-di-F-Ph Cl Br 407
55 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Me Me 105-108
56 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Me H 98-101(Ex. 18) 2,3,6-tri-F-Ph 4-Cl-Ph Cl CN 147-149
58 2,6-di-F-Ph 2-F-Ph Cl Br 113-115
2,6-di-F, 4-MeO, 3-
59 4-Cl-Ph Br Me 143-147 Me-Ph
64 2,6-di-F-Ph 2-F-Ph Cl Me 323
65 2,6-di-F-Ph 4-CF3O-Ph Cl Br 355
66 2,6-di-F-Ph 4-Br-Ph Cl Br 143-145
72 2,6-di-F-Ph 4-F-Ph Cl Br 389
73 2,6-di-F-Ph 3,5-di-F-Ph Cl Me 341
74 2-Cl, 3,6-di-F-Ph 4-Cl-Ph Cl H 360
75 3 -Br, 2,6-di-F-Ph 4-Cl-Ph Cl H 405
76 2-Cl, 3,6-di-F-Ph 4-Cl-Ph Cl Br 439
80 2-Cl, 3,6-di-F-Ph 4-Cl-Ph Cl Me 373
81 2,6-di-F-Ph 4-CF3O-Ph Cl Me 389
82 2,6-di-F-Ph 4-Me-Ph Cl Me 319
83 2,6-di-F-Ph 4-F-Ph Cl Me 323
84 2,6-di-F-Ph 4-CF3-Ph Cl Br 117-120
85 2,5-di-F-Ph 4-Cl-Ph Cl Br 114-117
86 2-CF3, 6-F-Ph 4-Cl-Ph Cl Br 455
90 2-Cl, 6-F-Ph 4-Cl-Ph Cl CF3 409
91 3 -Br, 2,6-di-F-Ph 4-Cl-Ph Cl Me 419
92 2,6-di-F-Ph 4-CF3-Ph Cl Me 373
93 2,5-di-F-Ph 4-Cl-Ph Cl Me 339
94 2-CF3, 6-F-Ph 4-Cl-Ph Cl Me 389
95 2,6-di-F-Ph Bn Cl Br 85-87
96 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Br MeO 141-144
97 2,6-di-F, 3-Me-Ph 4-Cl-Ph Cl H 339
98 4-Cl-Ph 2,4,6-tri-F-Ph Cl H 130-131
99 2,6-di-F-Ph 4-Cl-Bn Me2N H 348
100 3 -Cl, 2, 6-di-F-Ph 4-Cl-Ph Cl Br 439
101 2,6-di-F-Ph 3-Cl-Bn Cl Br 419 m.p. Αf ,+
Cmpd. Q1 Q2 R2 R4 (0C) (M+l)
102 2,6-di-F-Ph 4-Cl, 3-F-Bn Cl Br 437
103 2,6-di-F-Ph 4-Cl-Bn Cl Br 419
105 2,6-di-F, 3-Me-Ph 4-Cl-Ph Cl Br 419
106 2-F, 4-MeO-Ph 4-Cl-Ph Cl H 337
107 2,6-di-F, 3-Me-Ph 4-Cl-Ph Cl Me 353
108 2,6-di-F-Ph 4-Cl-Ph Cl Et 125-126
109 3-Br, 2-F, 4-MeO-Ph 4-Cl-Ph Cl Br 498
110 2-F, 4-MeO-Ph 4-Cl-Ph Cl Br 417
112 2,6-di-F, 3-MeO-Ph 4-Cl-Ph Cl H 356
113 2-F, 4-MeO-Ph 4-Cl-Ph Cl Me 351
114 2-F, 4-MeO, 3-Me-Ph 4-Cl-Ph Cl Me 365
116 2,6-di-F-Ph 4-Cl-Ph Cl z-Pr 106-108
117 2,6-di-F, 3-MeO-Ph 4-Cl-Ph Cl Br 435
118 2,6-di-F-Ph Bn Cl Me 319
119 2,6-di-F, 4-HO-Ph 4-Cl-Ph Cl Me 355
120 2,6-di-F-Ph 4-Cl, 3-F-Bn Cl Me 371
121 2,3,6-tri-F-Ph 4-F-Ph Cl H 327
122 2,6-di-F, 3-MeO-Ph 4-Cl-Ph Cl Me 369
123 2,3,6-tri-F-Ph 4-Me-Ph Cl H 323
124 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Cl H 361
126 2,6-di-F-Ph 3-Cl-Bn Cl Me 353
127 3-Cl, 2,6-di-F-Ph 4-Cl-Ph Cl Me 375
128 2,6-di-F-Ph 4-Cl-Bn Cl Me 353
129 2,3,6-tri-F-Ph 4-F-Ph Cl Cl 361
130 2,3,6-tri-F-Ph 4-Me-Ph Cl Cl 357
131 4-Cl-Ph 2,4,6-tri-F-Ph Cl Br 117-118
132 2-Cl, 6-F, 4-MeO-Ph 4-Cl-Ph Cl H 371
133 4-Cl, 2-F, 6-MeO-Ph 4-Cl-Ph Cl H 371
134 2,3,6-tri-F-Ph 4-F-Ph Cl Br 407
135 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Cl Cl 395
136 2,6-di-F, 4-MeO-Ph 4-F-Ph Cl H 339
137 2,4,6-tri-F-Ph 4-F-Ph Cl H 327
138 2,6-di-F, 4-MeO-Ph 4-Me-Ph Cl H 335
139 2,4,6-tri-F-Ph 4-Me-Ph Cl H 323
140 4-Cl, 2-F, 6-MeO-Ph 4-Cl-Ph Cl Br 451
141 2,3,6-tri-F-Ph 4-Me-Ph Cl Br 403 m.p. AP+
Cmpd. Q1 Q2 R2 R4
(0C) (M+1)
142 2,6-di-F, 4-MeO-Ph 4-F-Ph Cl Cl 373
143 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Cl Br 441
144 2,6-di-F, 4-MeO-Ph 4-F-Ph Cl Br 419
145 2,3,6-tri-F-Ph 4-F-Ph Cl Me 341
146 2,6-di-F, 4-MeO-Ph 4-Me-Ph Cl Cl 369
147 2,4,6-tri-F-Ph 4-F-Ph Cl Cl 361
148 2,6-di-F, 4-MeO-Ph 4-Me-Ph Cl Br 415
149 4-Cl, 2-F, 6-MeO-Ph 4-Cl-Ph Cl Me 387
150 4-Cl-Ph 2,6-di-F-Ph Cl Cl 123-126
151 2,6-di-F-Ph 4-Cl-Ph Me Me 146-148
152 2,4,6-tri-F-Ph 4-F-Ph Cl Br 407
153 2,4,6-tri-F-Ph 4-Me-Ph Cl Br 403
154 2,4,6-tri-F-Ph 4-Me-Ph Cl Cl 357
155 2,3,6-tri-F-Ph 4-Me-Ph Cl Me 337
156 4-EtO, 2,6-di-F-Ph 4-Cl-Ph Cl Me 383
157 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Cl Me 375
158 2,6-di-F, 4-MeO-Ph 4-F-Ph Cl Me 353
159 2,6-di-F, 4-MeO-Ph 4-Me-Ph Cl Me 349
160 2,6-di-F-Ph 3,4-di-F-Ph Cl H 327
161 2,6-di-F-Ph 3-F, 4-Me-Ph Cl H 323
162 4-Cl-Ph 2,6-di-F-Ph Br Br 156-158
163 4-Cl-Ph 2,6-di-F-Ph Cl H 182-184
164 4-Cl-Ph 2,6-di-F-Ph Cl Br 148-150
167 2,4,6-tri-F-Ph 4-F-Ph Cl Me 341
168 2,4,6-tri-F-Ph 4-Me-Ph Cl Me 337
169 2,6-di-F-Ph 3,4-di-F-Ph Cl Br 407
170 2,6-di-F-Ph 3-F, 4-Me-Ph Cl Br 403
171 2-Cl, 6-F, 4-MeO-Ph 4-Cl-Ph Cl Br 451
172 2-Cl, 6-F, 4-MeO-Ph 4-Cl-Ph Cl Me 385
173 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Br H 123-124
174 2,6-di-F-Ph 3,4-di-F-Ph Cl Me 341
175 2,6-di-F-Ph 3-F, 4-Me-Ph Cl Me 337
176 2-Cl, 3,6-di-F-Ph 4-F-Ph Cl H 343
177 2-Cl, 3,6-di-F-Ph 4-Me-Ph Cl H 339
178 2-Cl, 4-F-Ph 4-F-Ph Cl H 325
179 2-Cl, 4-F-Ph 4-Me-Ph Cl H 321 m.p. AT ,+
Cmpd. Q1 Q2 R2 R4
(0C) (M+1)
180 2-Cl, 6-F-Ph 4-F-Ph Cl H 325
181 2-Cl, 6-F-Ph 4-Me-Ph Cl H 321
182 2-Cl, 4-F-Ph 4-F-Ph Cl Br 111-112
183 2-Cl, 4-F-Ph 4-F-Ph Cl Cl 359
184 2-Cl, 4-F-Ph 4-Me-Ph Cl Br 127-128
185 2-Cl, 6-F-Ph 4-F-Ph Cl Br 95-97
186 2-Cl, 6-F-Ph 4-Me-Ph Cl Br 147-148
187 2-Cl, 4-F-Ph 4-F-Ph Cl Me 101-106
188 2-Cl, 4-F-Ph 4-Me-Ph Cl Me 148-149
189 2-Cl, 6-F-Ph 4-F-Ph Cl Me 122-123
190 2-Cl, 6-F-Ph 4-Me-Ph Cl Me 158-162
191 2-Cl, 4-F-Ph 4-Cl, 3-F-Ph Cl H 359
192 2-Cl, 6-F-Ph 4-Cl, 3-F-Ph Cl H 359
193 4-CN, 2,6-di-F-Ph 4-Cl-Ph Cl H 350
194 2,6-di-F-Ph 4-MeO-Bn Cl H 335
195 2-Cl, 3,6-di-F-Ph 4-F-Ph Cl Br 423
196 2-Cl, 3,6-di-F-Ph 4-F-Ph Cl Cl 378
197 2-Cl, 3,6-di-F-Ph 4-Me-Ph Cl Br 419
198 2-Cl, 3,6-di-F-Ph 4-Me-Ph Cl Cl 374
199 2,6-di-F-Ph 3-quinolinyl Cl Me 158-160
200 4-Cl-Ph 2,6-di-F-Ph Br H 195-197
201 4-CN, 2,6-di-F-Ph 4-Cl-Ph Cl Br 429
202 2-Cl, 4-F-Ph 4-Cl, 3-F-Ph Cl Br 103-104
203 2-Cl, 6-F-Ph 4-Cl, 3-F-Ph Cl Br 80-84
204 4-Cl-Ph 2,4,6-tri-F-Ph Cl Cl 76-78
205 4-CN, 2,6-di-F-Ph 4-Cl-Ph Cl Me 429
206 2-Cl, 3,6-di-F-Ph 4-F-Ph Cl Me 429
207 2-Cl, 3,6-di-F-Ph 4-Me-Ph Cl Me 429
208 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Cl H 429
209 2,6-di-F-Ph 4-Cl, 3-F-Ph Cl H 429
210 2,6-di-F-Ph 3-Cl-Ph Cl H 429
211 2,3,6-tri-F-Ph 3,4-di-Me-Ph Cl H 429
212 4-Cl-Ph 2,4,6-tri-F-Ph Br H 137-140
213 2,6-di-F-Ph 3-Cl, 4-MeO-Bn Cl Cl 405
214 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Br Cl 119-122
215 2,6-di-F, 3-MeS-Ph 4-Cl-Ph Cl H 371 m.p. AT ,+
Cmpd. Q1 Q2 R2 R4
(0C) (M+ 1)
216 4-Cl-Ph 2,6-di-F-Ph Me Br 156-158
217 2,6-di-F-Ph 4-Cl-Ph H2C=CH Me 141-143
218 4-Cl-Ph 2,4,6-tri-F-Ph Br Br 130-131
219 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Cl Br 457
220 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Cl Cl 413
221 2,6-di-F-Ph 3 -Cl-Ph Cl Br 405
222 2,6-di-F-Ph 3 -Cl-Ph Cl Cl 361
223 2,6-di-F-Ph 4-Cl, 3-F-Ph Cl Br 423
224 2,3,6-tri-F-Ph 3,4-di-Me-Ph Cl Br 417
225 2,6-di-F-Ph 4-Cl, 3-F-Ph Cl Cl 379
226 2,3,6-tri-F-Ph 3,4-di-Me-Ph Cl Cl 371
227 2-Cl, 6-F-Ph 4-Me-Ph Cl Cl 142-143
228 2-Cl, 6-F-Ph 4-F-Ph Cl Cl 102-103
229 2-Cl, 4-F-Ph 4-Cl, 3-F-Ph Cl Cl 116-117
230 2-Cl, 6-F-Ph 4-Cl, 3-F-Ph Cl Cl 66-67
231 2,6-di-F, 3-MeS-Ph 4-Cl-Ph Cl Br 451
232 3-ClCH2S, 2,6-di-F-Ph 4-Cl-Ph Cl H 405
233 4-Cl-Ph 2,4,6-tri-F-Ph Br Cl 111-112
234 2,3,6-tri-F-Ph 3,4-di-Cl-Ph Cl Cl 413
235 2,6-di-F, 3-MeS-Ph 4-Cl-Ph Cl Me 385
236 2,6-di-F-Ph 3 -Cl-Ph Cl Me 339
237 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Cl Me 393
238 2,3,6-tri-F-Ph 3,4-di-Me-Ph Cl Me 351
239 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Cl Cl 391
240 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Cl Cl 407
241 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Cl I 499
242 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Br Br 137-139
243 2-Cl, 4-F-Ph 4-Cl, 3-F-Ph Cl Me 89-91
244 2-Cl, 6-F-Ph 4-Cl, 3-F-Ph Cl Me 140-142
245 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Cl I 481
246 (Ex. 11) 2,6-di-F, 4-MeO-Ph 3-F-Ph Cl H 339
247 2,6-di-F-Ph 4-Cl, 3-F-Ph Cl Me 358
249 4-Cl-Ph 2,6-di-F,4-MeO-Ph Me Me 105-108
250 2,6-di-F, 4-MeO-Ph 2-pyridinyl Me H 302
251 2-pyridinyl 4-Cl, 3-F-Ph Me H 288
252 3-pyridinyl 4-Cl, 3-F-Ph Me H 288 m.p. AP+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
253 4-pyridinyl 4-Cl, 3-F-Ph Me H 288
254 2,6-di-F, 4-MeO-Ph 6-Cl-3-pyridinyl Me H 336
255 3,5-di-Cl-4-pyridinyl 4-Cl, 3-F-Ph Me H 356
256 (Ex. 12) 2,6-di-F, 4-MeO-Ph 3-F-Ph Cl Br 418
257 2,6-di-F, 4-MeO-Ph 3-F-Ph Cl Cl 373
258 2,6-di-F-Bn 4-Cl-Ph Cl Me 353
259 2-F-Ph 4-Cl, 3-F-Ph ClCH2 Cl 373
260 2-F-Ph 4-Cl, 3-F-Ph Me Cl 339
261 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Me Cl 387
262 3,5-di-Cl-4-pyridinyl 4-Cl, 3-F-Ph Me Cl 390
263 2,6-di-F, 4-MeO-Ph 6-Cl-3-pyridinyl Me Cl 370
264 2-pyridinyl 4-Cl, 3-F-Ph Me Cl 322
265 2,6-di-F, 4-MeO-Ph 4-Cl-Bn Me2N H 378
266 2,3,6-tri-F-Ph 4-Cl-Bn Cl H ** **
267 2,3,6-tri-F-Ph 4-Cl-Bn Me2N H ** **
268 2,6-di-F, 4-MeO-Ph 4-Cl-Bn Cl H ** **
269 2,6-di-F, 4-MeO-Ph 4-Cl-Bn Me2N H ** **
270 2,6-di-F, 3-MeO-Ph 4-Cl-Bn Cl H ** **
271 2,6-di-F, 3-MeO-Ph 4-Cl-Bn Me2N H ** **
272 4-Cl-Ph 3-Cl-Bn Cl H ** **
273 4-Cl-Ph 3-Cl-Bn Me2N H ** **
274 2,6-di-F, 4-MeO-Ph 4-Me-Bn Cl H ** **
275 2,6-di-F, 4-MeO-Ph 4-Me-Bn Me2N H ** **
276 (Ex. 20) 2,6-di-F, 4-MeO-Ph 4-F-Ph Cl HC(=O) ** **
277 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Cl H 147-148
278 2,6-di-F, 3-MeO-Ph 3-F-Ph Cl Br 419
279 2,6-di-F, 3-MeO-Ph 3-F-Ph Cl Cl 373
280 (Ex. 13) 2,6-di-F, 4-MeO-Ph 3-F-Ph Cl Me 354
281 2,6-di-F, 3-MeO-Ph 4-Me-Ph Cl Br 415
282 2-Cl, 4-F-Ph 4-Me-Ph Cl Cl 72-73
283 2,6-di-F, 4-MeO-Ph 4-Cl-Bn Cl Br 139-140
284 2,6-di-F, 4-MeO-Ph 4-Cl-Bn Cl Cl 123-124
285 2,3,6-tri-F-Ph 4-Cl-Bn Cl Cl ** **
286 2,3,6-tri-F-Ph 4-Cl-Bn Cl Br 87-88
287 2,6-di-F, 4-MeO-Ph 4-Cl-Bn Cl Me 116-117
288 2,6-di-F, 3-MeO-Ph 4-Cl-Bn Cl Cl ** ** m.p. AT ,+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
289 2,6-di-F, 3-MeO-Ph 4-Cl-Bn Cl Br 449
290 4-Cl-Ph 3-Cl-Bn Cl Br 108-109
291 2,6-di-F, 4-MeO-Ph 4-Me-Bn Cl Cl 383
292 2,6-di-F, 4-MeO-Ph 4-Me-Bn Cl Br 104-105
293 2,3,6-tri-F-Ph 4-Cl-Bn Cl Me 371
294 2,6-di-F, 3-MeO-Ph 4-Cl-Bn Cl Me 384
295 4-Cl-Ph 3-Cl-Bn Cl Me 113-114
296 2,6-di-F, 4-MeO-Ph 4-Me-Bn Cl Me 363
297 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Cl Cl 117-118
298 (Ex. 21) 2,6-di-F, 4-MeO-Ph 4-F-Ph Cl HOCH2 ** **
299 2,6-di-F, 3-MeO-Ph 4-F-Ph Cl H 340
300 2,6-di-F, 3-MeO-Ph 3-Me-Ph Cl H 336
301 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Br Br 104-106
302 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Cl Cl 120-122
303 2,6-di-F-Ph 2-naphthalenyl Cl Me 165-167
304 2,6-di-F-Ph 4-Cl-l-naphthalenyl Cl Me 172-175
305 2,6-di-F-Ph 4-Cl-Ph Et Me 122-124
306 4-Cl-Ph 2-Cl, 4-F-Ph Br Br 114-116
307 4-Cl-Ph 2-Cl, 4-F-Ph Me Me 336
308 4-Cl-Ph 2,4,6-tri-F-Ph Me Me 90-92
309 2,6-di-F, 3-MeO-Ph 4-Cl-Ph Cl Cl 391
310 2,6-di-F, 3-MeO-Ph 4-Me-Ph Cl Cl 369
314 2,6-di-F, 3-MeO-Ph 4-F-Ph Cl Br 419
315 2,6-di-F, 3-MeO-Ph 3-F-Ph Cl Me 353
316 2,6-di-F, 3-MeO-Ph 3-Me-Ph Cl Br 414
317 2,6-di-F, 3-MeO-Ph 4-Cl, 3-F-Ph Cl Br 453
318 2-F-Ph 4-Cl, 3-F-Ph Me H 305
319 2-F-4-pyridinyl 4-Cl, 3-F-Ph Me H 306
320 2,6-di-F-Ph 5-Cl-2-pyridinyl Me H ** **
321 2,6-di-F-Ph 5-Cl-2-pyridinyl Me Cl ** **
322 2-F-4-pyridinyl 4-Cl, 3-F-Ph ClCH2 Cl ** **
323 2-F-4-pyridinyl 4-Cl, 3-F-Ph Me Cl ** **
324 4-Cl-Ph 2-Cl, 4-F-Ph Br Cl 106-109
325 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Me Br 105-107
326 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Br Cl 116-118
327 2,6-di-F-Ph 6-quinolinyl Cl Br 176-180 m.p. AT ,+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
328 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Cl Br 120-122
329 4-Cl-Ph 2-Cl, 4-F-Ph Cl Br 113-116
330 2,3,6-tri-F-Ph 4-Cl-Ph Br H ** **
331 (Ex. 22) 2,6-di-F, 4-MeO-Ph 4-F-Ph Cl FCH2 ** **
332 2,3,6-tri-F-Ph 4-F-Ph Br H ** **
333 2,6-di-F, 3-MeO-Ph 4-Me-Ph Cl Me 349
334 2,6-di-F, 3-MeO-Ph 4-F-Ph Cl Me 353
335 2,6-di-F, 3-MeO-Ph 3-Me-Ph Cl Me 113-117
336 2,6-di-F-Ph 2-naphthalenyl Br Me 173-175
337 2,6-di-F-Ph 4-Cl-l-naphthalenyl Br Me 192-195
338 4-Cl-Ph 2-Cl, 4-F-Ph Br Me 127-131
339 4-Cl-Ph 2-Cl, 4-F-Ph Me Br 146-150
340 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Br Me 125-127
341 4-Cl-Ph 2,6-di-F-Ph H Cl 77-79
342 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Br H ** **
343 2-Cl, 3,6-di-F-Ph 4-Cl-Ph Br H ** **
345 2 -Br-4 -pyridinyl 4-Cl, 3-F-Ph Me H 366
346 5-Br-3-pyridinyl 4-Cl, 3-F-Ph Me H 366
347 5-Br-2 -pyridinyl 4-Cl, 3-F-Ph Me H ** **
348 2-C1-3 -pyridinyl 4-Cl, 3-F-Ph Me H 322
349 (Ex. 23) 2,6-di-F, 4-MeO-Ph 4-F-Ph Cl HON=CH ** **
350 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Br Cl ** **
351 2,3,6-tri-F-Ph 4-Cl-Ph Br Cl ** **
352 2,3,6-tri-F-Ph 4-F-Ph Br Cl ** **
353 2 -Br-4 -pyridinyl 4-Cl, 3-F-Ph ClCH2 Cl 434
354 2-Br-4-pyridinyl 4-Cl, 3-F-Ph Me Cl 400
355 5 -Br-3 -pyridinyl 4-Cl, 3-F-Ph ClCH2 Cl 434
356 5 -Br-3 -pyridinyl 4-Cl, 3-F-Ph Me Cl 400
357 5-Br-2 -pyridinyl 4-Cl, 3-F-Ph ClCH2 Cl ** **
358 5-Br-2-pyridinyl 4-Cl, 3-F-Ph Me Cl 400
359 2-C1-3 -pyridinyl 4-Cl, 3-F-Ph ClCH2 Cl 390
360 2-C1-3 -pyridinyl 4-Cl, 3-F-Ph Me Cl 356
361 4-Cl-Ph 3-Cl-Bn Cl Cl 107-109
362 2,4,6-tri-F-Ph 3-F-Ph Cl H 133-135
363 2,4,6-tri-F-Ph 3-F-Ph Me2N H ** **
364 2,3,6-tri-F-Ph 3-F-Ph Cl H 78-81 m.p. AP+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
365 2,4,6-tri-F-Ph 3-F-Ph Cl Cl 78-81
366 2,3,6-tri-F-Ph 3-F-Ph Cl Cl 143-145
367 2,4,6-tri-F-Ph 3-F-Ph Cl Br 130-132
368 2,3,6-tri-F-Ph 3-F-Ph Cl Br 137-138
369 2,3,6-tri-F-Ph 3-F-Ph Cl Me 146-147
370 2,4,6-tri-F-Ph 3-F-Ph Cl Me 150-152
4,5-di-Br, 1-Me-lH-
371 4-Cl-Ph Br Br 496 imidazol-2-yl
4,5-di-Br, I -Me-IH-
372 4-Cl-Ph Br Br 575 imidazol-2-yl
373 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Cl Br 118-125
374 2-Cl, 3,6-di-F-Ph 4-Cl-Ph Br Br ** **
375 6-Me-2-pyridinyl 4-Cl, 3-F-Ph Me H ** **
376 4-Cl-5-thiazolyl 4-Cl, 3-F-Ph Me H ** **
377 2,4-di-Cl-5-thiazolyl 4-Cl, 3-F-Ph Me H ** **
378 6-Me-2-pyridinyl 4-Cl, 3-F-Ph Me Cl ** **
379 6-Me-2-pyridinyl 4-Cl, 3-F-Ph ClCH2 Cl ** **
380 4-Cl-5-thiazolyl 4-Cl, 3-F-Ph Me Cl ** **
381 2,4-di-Cl-5-thiazolyl 4-Cl, 3-F-Ph Me Cl ** **
382 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Br Br ** **
383 2,3,6-tri-F-Ph 4-Cl-Ph Br Br 467
384 2,3,6-tri-F-Ph 4-F-Ph Br Br 449
385 2-Cl, 3,6-di-F-Ph 4-Cl-Ph Br Cl 439
386 (Ex. 29) 3-CN, 2,6-di-F-Ph 4-Cl-Ph Cl H 350
387 3 -CN, 2,6-di-F-Ph 4-CN-Ph Cl H 341
388 2-Cl, 3,6-di-F-Ph 4-Cl-Ph Me Me 353
389 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Me Cl ** **
390 2,6-di-F, 3-MeO-Ph 4-F-Ph Cl Cl 374
391 2,6-di-F, 3-MeO-Ph 3-Me-Ph Cl Cl 133-136
392 2,6-di-F, 3-MeO-Ph 4-Cl, 3-F-Ph Cl Cl 84-86
393 2,6-di-F, 3-MeO-Ph 4-Cl, 3-F-Ph Cl Me 387
5-Br, 4-Cl, 1-Me-lH-
394 4-Cl-Ph H Cl 407 imidazol-2-yl
396 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Me Cl 104-106
397 4-Cl-Ph 2,6-di-F, 4-MeO-Ph ClCH2 Cl 127-129
398 2,6-di-F, 3-MeO-Ph 3-Et-Ph Cl Br 429 m.p. AP+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
399 2,6-di-F, 3-MeO-Ph 4-Cl, 3-Me-Ph Cl Cl 403
400 2,6-di-F, 3-MeO-Ph 3-F2CHO-Ph Cl Cl 100-102
401 2,6-di-F, 3-MeO-Ph 4-Cl, 3-Me-Ph Cl Br 449
402 2,6-di-F, 3-MeO-Ph 3-F2CHO-Ph Cl Br 109-111
403 2,4-di-F-Bn 4-Cl-Ph H Me 320
404 2,4-di-F-Bn 4-Cl-Ph Br Me 399
3 -Cl, 2,6-di-F, 4-MeO-
405 4-Me-Ph Cl Cl ** ** Ph
406 2,6-di-F, 4-MeO-Ph 6-C1-3 -pyridinyl Cl Cl 390
407 3 -CN, 2,6-di-F-Ph 4-Cl-Ph Cl Cl 386
408 4-Br, 5-MeS-2-thienyl 4-Cl-Ph Br Br 545
409 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Br H ** **
410 2-Cl, 3,6-di-F-Ph 4-Me-Ph Br H ** **
411 2,3,6-tri-F-Ph 4-Me-Ph Br H ** **
412 2,3,6-tri-F-Ph 4-Cl-Ph Me Cl ** **
413 2,3,6-tri-F-Ph 4-F-Ph Me Cl ** **
414 2-Cl, 3,6-di-F-Ph 4-Cl-Ph Me Cl ** **
415 2,3,6-tri-F-Ph 4-Cl, 3-F-Ph Me Me ** **
416 2,3,6-tri-F-Ph 4-Cl-Ph Me Me ** **
417 2,3,6-tri-F-Ph 4-F-Ph Me Me ** **
418 2,6-di-F, 3-MeO-Ph 3-Et-Ph Cl Me 364 (Ex. 30) 3 -CN, 2,6-di-F-Ph 4-Cl-Ph Cl Br 430
420 2,6-di-F, 4-MeO-Ph Ph Cl H 321
421 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Cl Me 108-110
422 4-Cl-Ph 2-Cl, 4-F-Ph Cl Me 135-137
423 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Cl Me 108-110
425 2,6-di-F, 3-MeO-Ph 4-Cl, 3-Me-Ph Cl Me 383
426 2,6-di-F, 3-MeO-Ph 3-F2CHO-Ph Cl Me 401
427 2,6-di-F, 3-MeO-Ph 3-Et-Ph Cl Cl 93-95
3 -Cl, 2,6-di-F, 4-MeO-
428 Ph Cl Cl 391 Ph
3 -Br, 2,6-di-F, 4-MeO-
429 Ph Cl Br 479 Ph (Ex. 31) 3 -CN, 2,6-di-F-Ph 4-Cl-Ph Cl Me 364
433 6 -Br-2 -pyridinyl 4-Cl, 3-F-Ph Cl Cl 420
434 6-MeO-3 -pyridinyl 4-Cl, 3-F-Ph Cl Cl ** ** m.p. AP÷
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
435 3 -F, 5-MeO-4-pyridinyl 4-Cl, 3-F-Ph Cl Cl 390
436 3-quinolinyl 4-Cl, 3-F-Ph Cl Cl 392
437 2,6-di-Cl, 4-MeO-Ph 4-Cl, 3-F-Ph Cl Cl ** **
438 2,4-di-Cl, 6-MeO-Ph 4-Cl, 3-F-Ph Cl Cl ** **
2,6-di-F, 4-MeO, 3-
439 Ph Cl Me 349 Me-Ph
440 2,3,6-tri-F-Ph 3,4-di-Cl-Ph Cl Br 457
441 2,6-di-F, 3-MeO-Ph 4-Et-Ph Cl Br 429
442 2,6-di-F, 3-MeO-Ph 4-Et-Ph Cl Cl 383
443 2,6-di-F, 3-MeO-Ph 4-I-Ph Cl Br 134-138
444 2,6-di-F, 3-MeO-Ph 4-I-Ph Cl Cl 481
445 4-Cl-Ph 2,4,6-tri-F-Ph Me Br 123-125
446 4-Cl-Ph 2,4,6-tri-F-Ph Me Cl 86-88
447 4-Cl-Ph 2,4,6-tri-F-Ph Me H 110-112
448 2,6-di-F, 3-MeO-Ph 4-I-Ph Cl H 447
449 2,6-di-F, 3-MeO-Ph 4-Cl-Ph Br H 401
450 (Ex. 14) 2,6-di-F, 3-MeO-Ph 4-F-Ph Br H ** **
3 -Cl, 5-ClCH2, 4-Me-
451 4-Cl-Ph H Cl 393 2-thienyl
5-ClCH2, 4-Me-2-
452 4-Cl-Ph H Cl 359 thienyl
453 2,6-di-F, 4-MeO-Ph 3 -Cl-Ph Cl Cl ** **
454 2,6-di-F, 4-MeO-Ph 3,4-di-F-Ph Cl Cl 391
455 3-F-4-pyridinyl 4-Cl, 3-F-Ph Cl Cl 360
4-Cl, 2-MeO-5-
456 4-Cl, 3-F-Ph Cl Cl 412 thiazolyl
457 4-Cl-5-thiazolyl 4-Cl, 3-F-Ph Cl Cl 482
458 2-Cl-3-pyridinyl 4-Cl, 3-F-Ph Cl Cl 376
459 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Br Br ** **
460 2-Cl, 3,6-di-F-Ph 4-Me-Ph Br Br ** **
461 2,3,6-tri-F-Ph 4-Me-Ph Br Br ** **
462 2,4,6-tri-F-Ph 4-F-Ph Br Br ** **
463 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Br Cl ** **
464 2-Cl, 3,6-di-F-Ph 4-Me-Ph Br Cl ** **
465 2,3,6-tri-F-Ph 4-Me-Ph Br Cl ** **
466 4-Cl-Ph 2,6-di-F-Ph Me Cl 127-129 m.p. AP+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
467 4-Cl-Ph 2,6-di-F-Ph MeOCH2 Cl 95-97
468 2,6-di-F-Ph 6-quinolinyl Cl Me 210-215
2,3-dihydro-l,4-
469 2,6-di-F-Ph Cl ClCH2 142-144 benzodioxin-6-yl
2,3-dihydro-l,4-
470 2,6-di-F-Ph Cl Me 122-124 benzodioxin- 6 -yl
471 2,6-di-F, 3-MeO-Ph 4-Cl-Ph Br Br ** **
472 2,6-di-F, 3-MeO-Ph 4-F-Ph Br Cl 417
473 2,6-di-F, 3-MeO-Ph 4-Me-Ph Br H 380
475 (Ex. 24) 2,6-di-F-Ph 4-Cl-Ph Br BrCH2 463
476 2,4-di-F-Bn 3,5-di-MeO-Ph H Me 345
477 2,4-di-F-Bn 2,6-di-Br, 3,5-di-MeO-Ph Br Me 582
479 2,6-di-F, 3-MeO-Ph 4-Et-Ph Cl Me 364
480 2,3,6-tri-F-Ph 3,4-di-Cl-Ph Cl Me 391
481 2-Cl, 6-F, 3-MeO-Ph 4-Cl-Ph Cl Cl 407
482 2-Cl, 6-F, 5-MeO-Ph 4-Cl-Ph Cl H 373
483 2,6-di-F, 4-MeO-Ph 3 -Cl-Ph Cl Br 435
484 2,6-di-F, 4-MeO-Ph 3,4-di-F-Ph Cl Br 437
485 2 -Br-4 -pyridinyl 4-Cl, 3-F-Ph Cl Cl 420
486 5-Br-3-pyridinyl 4-Cl, 3-F-Ph Cl Cl 420
487 5-Br-2 -pyridinyl 4-Cl, 3-F-Ph Cl Cl ** **
488 2,6-di-F, 4-MeO-Ph 6-CF3-3-pyridinyl Cl Cl ** **
489 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Me Me ** **
490 2,3,6-tri-F-Ph 4-Me-Ph Me Me ** **
491 2,4,6-tri-F-Ph 4-F-Ph Me Me ** **
492 2,4,6-tri-F-Ph 4-F-Ph Me Cl ** **
493 2-Cl, 3,6-di-F-Ph 4-Me-Ph Me Me ** **
494 2-Cl, 3,6-di-F-Ph 4-Cl, 3-F-Ph Me Cl ** **
495 2-Cl, 3,6-di-F-Ph 4-Me-Ph Me Cl ** **
496 2,3,6-tri-F-Ph 4-Me-Ph Me Cl ** **
497 2,6-di-F, 4-MeO-Ph 3 -Cl-Ph Cl H 114-115
498 2,6-di-F, 4-MeO-Ph 3,4-di-F-Ph Cl H 115-116
499 2,6-di-F, 4-MeO-Ph 3,4-di-F-Ph Cl Me 169-170
500 2,6-di-F, 4-MeO-Ph 3 -Cl-Ph Cl Me 173-174
501 2-Cl, 6-F, 3-MeO-Ph 4-Cl-Ph Cl Br 154-156
502 2,6-di-F, 4-MeO-Ph 3 -Cl, 4-Me-Ph Cl Cl 143-145 m.p. AP+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
503 4-Cl-Ph 2-Cl, 4-F-Ph Me Cl 123-127
504 (Ex. 15) 2,6-di-F, 3-MeO-Ph 4-F-Ph Br Br 134-136
505 2,6-di-F, 4-MeO-Ph 4-Me-Ph Br H 385
506 2,6-di-F, 4-MeO-Ph 4-F-Ph Br H ** **
507 2,4,6-tri-F-Ph 4-F-Ph Br H ** **
508 2-Cl, 3,6-di-F-Ph 4-F-Ph Br H ** **
509 (Ex. 25) 2,6-di-F-Ph 4-Cl-Ph Br N≡CCH2 410
510 2,6-di-F, 3-MeO-Ph 4-Cl-Ph Br Cl ** **
511 2,6-di-F, 3-MeO-Ph 4-Me-Ph Br Br 459
512 2-Cl, 6-F, 5-MeO-Ph 4-Cl-Ph Cl Br 451
513 2,6-di-F, 4-MeO-Ph 2-Cl-3-pyridinyl Cl Cl 390
514 2,6-di-F, 4-MeO-Ph 6-Cl, 2-MeO-3-pyridinyl Cl Cl ** **
515 2,6-di-F, 4-MeO-Ph 2-Cl, 6-MeO-3-pyridinyl Cl Cl 420
516 2,6-di-F, 4-MeO-Ph 6-MeO-3 -pyridinyl Cl Cl 386
517 2,6-di-F, 3-MeO-Ph 4-Me-Ph Br Cl 415
518 2-Cl, 6-F, 5-MeO-Ph 4-Cl-Ph Cl Cl 407
519 2-Cl, 6-F, 3-MeO-Ph 4-Cl-Ph Cl Me 387
520 2,6-di-F, 3-MeO-Ph 3 -F, 4-Me-Ph Cl H 354
521 2,6-di-F, 4-MeO-Ph 4-Me-Ph Me Me ** **
522 2,6-di-F, 4-MeO-Ph 4-F-Ph Me Me ** **
523 2,6-di-F, 4-MeO-Ph 4-F-Ph Br Br ** **
524 2,6-di-F, 4-MeO-Ph 4-Me-Ph Br Br ** **
525 4-Me-Ph 2,6-di-F, 4-MeO-Ph Me Br 128-129
526 2,6-di-F, 3-MeO-Ph 4-Cl-Ph Me Cl 369
527 2,6-di-F, 3-MeO-Ph 4-CN-Ph Cl H 346
528 2,6-di-F, 3-MeO-Ph 4-Br-Ph Cl H 401
529 2,6-di-F-Ph 4-ClCH2S-Ph Cl Me 386
530 2,4,6-tri-F-Bn 4-Cl-Ph H Me 338
531 2,4,6-tri-F-Bn 4-Cl-Ph Cl Me 372
532 2,4,6-tri-F-Bn 4-Cl-Ph Br Me 417
533 2,4,6-tri-F-Bn 3,5-di-MeO-Ph H Me 363
534 2,4,6-tri-F-Bn 3,5-di-MeO-Ph Cl Me 398
535 2,4,6-tri-F-Bn 3,5-di-MeO-Ph Br Me 442
536 2,4,6-tri-F-Bn 2,6-di-Cl-Ph H Me 372
537 2,4,6-tri-F-Bn 2,6-di-Cl-Ph Cl Me 407
538 2,4,6-tri-F-Bn 2,6-di-Cl-Ph Br Me 451 m.p. AT ,+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
539 2,4,6-tri-F-Bn 3,5-di-Cl-Ph H Me 372
540 2,4,6-tri-F-Bn 3,5-di-Cl-Ph Cl Me 407
541 2,4,6-tri-F-Bn 3,5-di-Cl-Ph Br Me 451
542 2,6-di-F, 4-MeO-Ph 3 -Cl, 4-Me-Ph Cl Br 161-163
543 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Me Me 354
544 (Ex. 26) 2,6-di-F-Ph 4-Cl-Ph Br MeOC(O)CH2 443
545 2,6-di-F, 4-MeO-Ph 3-F2CHO-Ph Cl Br 467
546 2,6-di-F, 4-MeO-Ph 4-F2CHO-Ph Cl Br 467
547 2,6-di-F, 4-MeO-Ph 3-CF3O-Ph Cl Br 485
548 2,6-di-F, 4-MeO-Ph 4-CF3O-Ph Cl Br 80-82
549 (Ex. 16) 2,6-di-F, 3-MeO-Ph 4-F-Ph Me Me 333
550 2-Cl, 6-F, 5-MeO-Ph 4-Cl-Ph Cl Me 387
551 2,6-di-F, 3-MeO-Ph 3 -F, 4-Me-Ph Cl Br 432
552 2,6-di-F, 3-MeO-Ph 4-CN-Ph Cl Cl 191-193
553 2,6-di-F, 4-MeO-Ph 6-Me-3-pyridinyl Cl Cl 370
554 2,6-di-F, 4-MeO-Ph 6-Me-3-pyridinyl Br Br 458
555 2,6-di-F, 4-MeO-Ph 6-Me-3-pyridinyl Br H 380
556 2,6-di-F, 4-MeO-Ph 3-F2CHO-Ph Cl H 102-103
557 2,6-di-F, 4-MeO-Ph 4-F2CHO-Ph Cl H 74-76
558 2,6-di-F, 4-MeO-Ph 3-CF3O-Ph Cl H 85-86
559 2,6-di-F, 4-MeO-Ph 4-CF3O-Ph Cl H 115-116
560 4-Me-Ph 2,6-di-F, 4-MeO-Ph Me H 114-118
561 2,6-di-F, 3-MeO-Ph 3 -F, 4-Me-Ph Cl Cl 387
562 2,6-di-F, 3-MeO-Ph 4-Br-Ph Cl Cl 435
563 2,6-di-F, 3-MeO-Ph 4-Br-Ph Cl Br 479
564 4-Me-Ph 2,6-di-F, 4-MeO-Ph Me Cl 121-122
565 2,6-di-F, 4-MeO-Ph 3-F2CHO-Ph Cl Cl 68-70
566 2,6-di-F, 4-MeO-Ph 4-F2CHO-Ph Cl Cl 421
567 2,6-di-F, 4-MeO-Ph 3-CF3O-Ph Cl Cl 94-95
568 2,6-di-F, 4-MeO-Ph 4-CF3O-Ph Cl Cl 90-91
569 2,6-di-F, 4-MeO-Ph 4-F2CHO-Ph Cl Me 401
570 (Ex. 27) 2,6-di-F-Ph 4-Cl-Ph Br HOC(=O)CH2 429
571 (Ex.28) 2,6-di-F-Ph 4-Cl-Ph Br MeNHC(=O)CH2 442
572 2,6-di-F, 4-MeO-Ph 3 -CN, 4-Me-Ph Cl Cl 141-143
573 4-Cl, 3-F-Ph 2-Cl, 4-F-Ph Me Cl 106-109
574 2,6-di-Cl, 4-MeO-Ph 4-Cl, 3-F-Ph Cl Br ** ** m.p. AT ,+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
575 4-CN, 2-F, 6-MeO-Ph 4-Cl, 3-F-Ph Cl Cl ** **
576 2,6-di-F, 4-MeO-Ph 2 -Br- 3 -pyridinyl Cl Cl ** **
577 2,6-di-F-Ph 5-Me-2-pyridinyl Cl Cl ** **
581 4-Me-Ph 2,6-di-F, 4-MeO-Ph ClCH2 Cl ** **
582 2,6-di-F, 3-MeO-Ph 4-Br-Ph Cl Me 415
583 (Ex. 17) 2,6-di-F, 3-MeO-Ph 3-F2CHO-Ph Cl H2C=CH 413
584 2,4,6-tri-F-Ph 3-F2CHO-Ph Cl H 375
585 2,4,6-tri-F-Ph 4-F2CHO-Ph Cl H 375
586 2,4,6-tri-F-Ph 3-CF3O-Ph Cl H 393
587 2,4,6-tri-F-Ph 4-CF3O-Ph Cl H 393
588 2,6-di-F, 4-MeO-Ph 3-F2CHO-Ph Cl Me 401
589 2,6-di-F, 4-MeO-Ph 3-CF3O-Ph Cl Me 419
590 2,6-di-F, 3-MeO-Ph 3 -F, 4-Me-Ph Cl Me 367
591 2,6-di-F-Ph Ph Cl Cl 325
592 2,6-di-F-Ph 6-C1-3 -pyridinyl Cl Cl ** **
593 3 , 5 -di-F-4-pyridinyl 4-Cl, 3-F-Ph Cl Cl ** **
594 3 , 5 -di-F-4-pyridinyl 4-Cl, 3-F-Ph Cl H ** **
596 2,6-di-F, 3-MeO-Ph 4-CN-Ph Cl Br 426
597 2,4,6-tri-F-Ph 3-F2CHO-Ph Cl Cl 82-83
598 2,4,6-tri-F-Ph 4-F2CHO-Ph Cl Cl 91-92
599 2,4,6-tri-F-Ph 3-CF3O-Ph Cl Cl 76-77
600 2,4,6-tri-F-Ph 4-CF3O-Ph Cl Cl 75-76
601 2,6-di-F, 4-MeO-Ph 3 -Cl, 4-Me-Ph Cl Me 143-145
2,3-dihydro-l,4-
602 2,6-di-F-Ph Br Me 203-207 benzodioxin- 6 -yl
603 2,4,6-tri-F-Ph 3-CF2HO-Ph Cl Br 89-90
604 2,4,6-tri-F-Ph 4-F2CHO-Ph Cl Br 94-95
605 2,4,6-tri-F-Ph 3-CF3O-Ph Cl Br 80-81
606 2,4,6-tri-F-Ph 4-CF3O-Ph Cl Br 87-88
607 2,6-di-F, 4-MeO-Ph 3 -CN, 4-Me-Ph Cl Br 145-147
2,2-difluoro-l,3-
608 2,6-di-F-Ph Cl Me 100-105 benzodioxol-5-yl
609 2,4,6-tri-F-Ph 3-F2CHO-Ph Cl Me 389
610 2,4,6-tri-F-Ph 4-F2CHO Ph Cl Me 96-97
611 2,4,6-tri-F-Ph 3-CF3O-Ph Cl Me 93-94
612 2,4,6-tri-F-Ph 4-CF3O-Ph Cl Me 81-82 m.p. AP+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
613 2,6-di-F, 4-MeO-Ph 3 -CN, 4-Me-Ph Cl Me 123-125
614 2,6-di-F-Ph 4-MeOC(=O)-Ph Cl H 132-133
615 2,6-di-F, 3-MeO-Ph 4-CN-Ph Cl Me 360
616 2,6-di-F-Ph 2-MeO-3 -pyridinyl Cl Cl ** **
617 2,6-di-F-Ph 2-Cl-3-pyridinyl Cl Cl 360
618 2,6-di-F-Ph 2-C1-3 -pyridinyl Br Br 448
619 2,6-di-F-Ph 6-Cl, 2-MeO-3 -pyridinyl Cl Cl 390
620 2,6-di-F-Ph 2-Cl, 6-MeO-3 -pyridinyl Cl Cl 390
621 2,6-di-F-Ph 6-MeO-3 -pyridinyl Cl Cl 356
622 2,6-di-F-Ph 6-MeO-3 -pyridinyl Br Br 444
623 3 -Br, 2,6-di-F-Ph 3-F-Ph Cl H 389
624 (Ex. 32) 2,6-di-F, 4-OH-Ph 4-Me-Ph Cl Me 335
631 2,6-di-F, 4-F2CHO-Ph 4-Me-Ph Cl Me 385
632 (Ex. 9) 2,6-di-F, 4-MeO-Ph 3,5-di-MeO-Ph Me H *** ***
633 2,6-di-F-Ph 4-CH3OC(O)-Ph Me2N H 203-204
634 2,6-di-F-Ph 4-Me2N-Ph Me2N H 143-144
635 2,6-di-F-Ph 4-Me2N-Ph Cl H 164-165
636 2,6-di-F-Ph 4-CH3C(O)NH, 3-Cl-Ph Cl Cl 171-172
637 2,6-di-F-Ph 4-CH3C(O)NH-Ph Cl Cl 191-195
638 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Cl NH2 371
641 2-F, 4-Cl-Ph 2-Cl, 3,5-di-MeO-Ph Br H 447
642 2-F, 4-Cl-Ph 2-Br, 6-Cl, 3,5-di-MeO-Ph Br H 525
643 2,6-di-F-Ph 4-CH3C(=O)NH-Ph Cl Br 224-225
645 2,6-di-F, 4-MeO-Ph 3 -Cl, 4-MeO-Ph Cl Br 126-128
646 2,6-di-F, 4-MeO-Ph 3 -Cl, 4-MeO-Ph Cl Cl 113-115
647 2,6-di-F, 4-MeO-Ph 3-1, 4-Me-Ph Cl Cl 105-107
649 2,6-di-F-Ph 4-MeOC(O)-Ph Cl Cl 173-174
650 2,6-di-F-Ph 3 -Cl, 4-Me2N-Ph Cl H 181-182
651 3,5-di-MeO-Ph 2,6-di-F, 4-NO2-Ph Br Me 456
652 2,6-di-F-Ph 3,5-di-Cl, 4-Me2N-Ph Cl H 117-120
653 2,6-di-F,4-MeO-Ph 2-F, 4-Me-Ph Cl Cl 120-122
654 2,6-di-F, 4-MeO-Ph 2-F, 4-Me-Ph Cl Br 144-146
655 2,6-di-F, 4-MeO-Ph 3-1, 4-Me-Ph Cl Br 127-129
656 3 -CN, 2,6-di-F-Ph 4-F-Ph Cl H 334
657 2,6-di-F, 4-MeO-Ph 3,5-di-MeO-Ph Me Br 441
658 2,6-di-F, 4-MeO-Ph 2,6-di-Br, 3,5-di-MeO-Ph Me Br 599 m.p. AP+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
659 2,6-di-F, 4-MeO-Ph 2,6-di-Br, 3,5-di-MeO-Ph Me H 518
660 3-EtO, 2,6-di-F-Ph 4-Cl-Ph Cl H 369
661 3-EtO, 2,6-di-F-Ph 3-F-Ph Cl H 353
662 3-EtO, 2,6-di-F-Ph 4-Cl-Ph Cl Br 449
663 3-EtO, 2,6-di-F-Ph 3-F-Ph Cl Br 433
664 3-EtO, 2,6-di-F-Ph 4-Cl-Ph Cl Cl 403
665 3-EtO, 2,6-di-F-Ph 3-F-Ph Cl Cl 487
666 2,6-di-F-Ph 6-Cl-3-pyridinyl Cl Me 341
667 2,6-di-F, 4-MeO-Ph 6-Cl-3-pyridinyl-CH2 Cl Cl 404
3 -Cl, 2,6-di-F, 4-MeO-
668 6-Cl-3-pyridiny-CH2 Cl Cl 440 Ph
669 2,6-di-F, 4-MeO-Ph 6-Cl-3-pyridinyl-CH2 Cl H 127-128
670 2,6-di-F, 4-MeO-Ph 6-Cl-3-pyridinyl-CH2 Cl Br 450
671 2,6-di-F, 4-MeO-Ph 6-Me-3 -pyridinyl-CH2 Cl Me 364
672 2,6-di-F, 4-MeO-Ph 4-Cl-Ph OH Me ** **
6-CH3C(=O)NH-3-
673 2,6-di-F, 4-MeO-Ph Cl Cl 413 pyridinyl
674 2,6-di-F, 4-MeO-Ph 2,6-di-Cl-3-pyridinyl Cl Cl 424
675 2,6-di-F, 4-MeO-Ph 2-Me-3-pyridinyl Cl Cl 370
676 2,6-di-F, 4-MeO-Ph 2-MeO-3 -pyridinyl Cl Cl 386
677 2,6-di-F, 4-MeO-Ph 2-Cl, 5-Me-3-pyridinyl Cl Cl 404
678 2,6-di-F, 4-MeO-Ph 5-Br-3-pyridinyl Cl Cl 434
679 3 -CN, 2,6-di-F-Ph 4-F-Ph Cl Cl 368
680 3 -CN, 2,6-di-F-Ph 4-Me-Ph Cl Cl 364
681 3 -CN, 2,6-di-F-Ph 3-F-Ph Cl Cl 368
682 2,6-di-F-Ph 6-C1-3 -pyridinyl Me Br 386
683 3-F-Ph 2,6-di-F, 4-MeO-Ph Me H 128-130
684 3-EtO, 2,6-di-F-Ph 4-Cl-Ph Cl Me 383 (Ex. 37) 6-Cl-3-pyridinyl 2,6-di-F, 4-MeO-Ph Me H 117-118
686 3-F-Ph 2,6-di-F, 4-MeO-Ph Me Cl ** **
687 3-F-Ph 2,6-di-F, 4-MeO-Ph Me Br 113-114
688 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Me H 145-148
689 2,6-di-F-Ph 3 -Br, 4-Me2N-Ph Me2N Br 150-151
690 2,6-di-F-Ph 4-MeOC(=O)-Ph Cl Br 186-187
691 3 -CN, 2,6-di-F-Ph 6-C1-3 -pyridinyl Cl Cl 387
692 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Cl MeNH 385 m.p. AP+
Cmpd. Q1 Q2 R2 R4 (0C) (M+l)
693 2,6-di-F-Ph 6-Cl-3-pyridinyl Me Cl 341
694 (Ex. 10) 2,6-di-F, 4-MeO-Ph 3,5-di-MeO-Ph Me Cl *** ***
695 2,6-di-F, 4-MeO-Ph 4-Me-Ph Cl MeS 381
696 (Ex. 38) 6-Cl-3-pyridinyl 2,6-di-F, 4-MeO-Ph Me Cl 94-95
697 3 -CN, 2, 6-di-F-Ph 6-Cl-3-pyridinyl H Cl 351
698 4-MeO-Ph 2,4-di-Cl-Ph Cl Cl 389
699 2,6-di-F, 4-MeO-Ph 6-CF3-3-pyridinyl H Cl 390
700 4-Cl-Ph 2,6-di-F, 4-NO2-Ph H Me 350
701 3 -CN, 2,6-di-F-Ph 6-Cl-3-pyridinyl Cl Br 429
702 4-EtO, 2,6-di-F-Ph 4-F-Ph Cl H 353
703 4-EtO, 2,6-di-F-Ph 3-F-Ph Cl H 353
705 2,6-di-F, 4-MeO-Ph 6-MeO-3 -pyridinyl Cl Br 432
706 2,6-di-F, 4-MeO-Ph 6-CF3-3-pyridinyl Br Cl 470
707 (Ex. 35) 2,6-di-F, 4-MeO-Ph 6-CF3 -3 -pyridinyl Cl Br 470
708 4-Cl-Ph 2,6-di-F, 4-NO2-Ph Cl Me 384
709 2,6-di-F, 3-MeO-Ph 6-C1-3 -pyridinyl Cl Cl 392
710 2,6-di-F, 4-MeO-Ph 6-MeO-3 -pyridinyl Br Cl 432
711 2,6-di-F-Ph 6-C1-3 -pyridinyl Cl Br 406
712 3-F-Ph 2,6-di-F, 4-MeO-Ph ClCH2 Cl
713 (Ex. 36) 2,6-di-F, 4-MeO-Ph 6-CF3-3-pyridinyl Cl Me 404
714 2,6-di-F, 4-MeO-Ph 6-MeO-3 -pyridinyl Cl Me 366
715 3 -CN, 2,6-di-F-Ph 6-C1-3 -pyridinyl Me Br 409
716 3 -CN, 2,6-di-F-Ph 6-C1-3 -pyridinyl Me Cl 365
717 3 -CN, 2,6-di-F-Ph 6-C1-3 -pyridinyl ClCH2 Cl 401
718 2,6-di-F-Ph 6-MeO-3 -pyridinyl Me Cl 337
719 2,6-di-F-Ph 6-MeO-3 -pyridinyl Me Br 381
723 4-EtO, 2,6-di-F-Ph 4-Me-Ph Cl H 349
724 3-EtO, 2,6-di-F-Ph 3-F-Ph Cl Me 367
725 2-Cl, 4-MeO-Ph 4-F-Ph Cl Br 115-118
726 2-Cl, 4-MeO-Ph 4-F-Ph Cl H 112-114
3,5-di-Cl-2-pyridinyl-
727 2,6-di-F, 4-MeO-Ph Cl Cl 452 CH(Me)
728 2,6-di-F, 4-MeO-Ph 5-F-3-pyridinyl Cl Cl 374
729 2,6-di-F, 4-MeO-Ph 6-C1-3 -pyridinyl Cl Br 434
730 2,6-di-F, 3-MeO-Ph 6-C1-3 -pyridinyl Cl Br 436
731 2,6-di-F, 4-MeO-Ph 6-CF3-3-pyridinyl Me Br 450 m.p. AP+
Cmpd. Q1 Q2 R2 R4 (0C) (M+ 1)
732 2,6-di-F, 4-MeO-Ph 6-CF3-3-pyridinyl Me Cl 404
733 2,6-di-F, 3-MeO-Ph 6-Cl-3-pyridinyl Me Cl 370
2,6-di-F, A-
734* (MeNHCH2CH2CH2)- 4-Me-Ph Cl Me 406 (Ex. 33) Ph
735 2,6-di-F, 3-MeO-Ph 6-Cl-3-pyridinyl Me Br 416
736 2,6-di-F, 4-MeO-Ph 6-MeO-3 -pyridinyl Me Br 412
737 2,6-di-F, 4-MeO-Ph 6-MeO-3 -pyridinyl Me Cl 366
738 2,6-di-F, 3-MeO-Ph 6-C1-3 -pyridinyl Cl Me 370
739 2,6-di-F, 4-MeO-Ph 6-C1-3 -pyridinyl Cl Me 370
740 (Ex. 6) 2,6-di-F-Ph 4-Cl-Ph Br Me
74UEx. 43) 2.6-di-F. 4-MeO-Ph 4-CNS-Ph Cl H
* HCl salt.
** See Index Table D for IH NMR data.
*** See synthesis example for ^H NMR data.
INDEX TABLE B
Figure imgf000232_0001
Cmpd. Q1 Q3 Rl R3 m.p. (0C) AP+ (M+ 1)
26 Ph 2,4-di-F-Ph Me Me ** **
31 Ph 2-Cl, 4-F-Ph Me Me ** **
60 (Ex. 40) 2,6-di-F-Ph 3-F-Ph Me Me 303
61 2-Cl, 6-F-Ph 4-Cl-Ph Me Me 335
62 2-Cl, 6-F-Ph 3-F-Ph Me Me 319
63 2-Cl, 6-F-Ph 4-Cl, 3-F-Ph Me Me 353
67 4-Cl, 3-F-Ph 2,6-di-F-Ph Me Me 337
68 2,6-di-F-Ph 4-Cl, 3-F-Ph Me Me 337
69 2,4,6-tri-F-Ph 4-Cl-Ph Me Me 337
70 2,4,6-tri-F-Ph 3-F-Ph Me Me 321
71 2,4,6-tri-F-Ph 4-Cl, 3-F-Ph Me Me 355
77 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Me Me 349
78 2,6-di-F, 4-MeO-Ph 3-F-Ph Me Me 333 Cmpd. ϊl Rl R3 m.p. (0C) AP+ (M+ 1)
79 2,6-di-F, 4-MeO-Ph 4-Cl, 3-F-Ph Me Me 367
87 2,6-di-Cl-Ph 4-Cl-Ph Me Me 351
2,6-di-Cl-Ph 3-F-Ph Me Me 335
2,6-di-Cl-Ph 4-Cl, 3-F-Ph Me Me 369
104 4-Cl, 3-F-Ph 2,4,6-tri-F-Ph Me Me 355
111 4-Cl, 3-MeO-Ph 2,6-di-F, 4-MeO-Ph Me Me 379
115 4-Cl, 3-F-Ph 2,6-di-F, 4-MeO-Ph Me Me 367 125 (Ex. 39) 4-Cl-Ph 2,6-di-F-Ph Me Br 385
165 4-Cl-Ph 2,6-di-F-Ph Et Br **
166 4-Cl-Ph 2,4,6-tri-F-Ph Me Br 403
311 3-F-Bn 2-Cl, 4-F-Ph Me Me 333
312 4-F-Bn 2-Cl, 4-F-Ph Me Me 333 313 (Ex. 41) 2,4-di-F-Bn 2-Cl, 4-F-Ph Me Me 351
344 4-Cl-Bn 2-Cl, 4-F-Ph Me Me 349
424 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Me Br 125-126
431 2,6-di-F, 4-MeO-Ph 4-I-Ph Me MeO 122-124
432 2-Cl, 4-F-Ph 4-I-Ph Me MeO 112-114
578 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Me MeO 365
579 2,6-di-F, 4-MeO-Ph 4-F-Ph Me MeO 349
580 2,6-di-F, 4-MeO-Ph 4-MeO-Ph Me MeO 361 ** See Index Table D for IH NMR data.
INDEX TABLE C
Figure imgf000233_0001
Cmpd. R2 AP+ (M+ 1)4 (Ex.42) 2,4-di-F-Ph 4-Cl-Ph Cl 326
30 2,4-di-F-Ph 4-Cl-Ph Me 306
474 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Br 402
478 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Cl 356
595 4-Cl-Ph 2,6-di-F, 4-MeO-Ph Me 336
626 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Cl 356
627 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Br 402
628 2,6-di-F, 4-MeO-Ph 4-Cl-Ph Me 336 Cmpd. Q1 Q2 R2 AP+ (M+!)
644 4,6-di-Me-2-pyrimidinyl 3,5-di-Cl-Ph H 320
INDEX TABLE D
Cmpd. ^H NMR Data (CDCI3 solution unless indicated otherwise)a
26 δ 7.38-7.32 (m, 3H), 122-1 Al (m, 2H), 7.05-6.92 (m, IH), 6.83-6.70 (m, 2H), 3.79 (s, 3H),
2.24 (s, 3H).
31 δ 7.30-7.25 (m, 3H), 7.20-7.11 (m, 3H), 7.08-7.00 (m, IH), 6.90-6.83 (m, IH), 3.82 (s, 3H),
2.17 (s, 3H).
32 δ 7.43 (t, IH), 7.03 (dd, IH), 6.95 (d, IH), 6.43 (d, 2H), 3.78 (s, 3H).
45 δ 7.36-7.30 (m, 2H), 7.08-7.01 (m, 2H), 6.66-6.57 (m, 2H), 2.30 (s, 3H), 2.14 (s, 3H).
165 δ 7.34 (d, 2H), 7.30-7.21 (m, IH), 7.17 (d, 2H), 7.93-7.82 (m, 2H), 4.08 (q, 2H), 1.43 (t, 3H).
266 δ 7.55 (s, IH), 7.29-7.20 (m, 4H), 6.90 ( d, 2H), 4.96 (s, 2H).
267 δ 7.12 (d, 2H), 7.12-7.01 (m, IH), 6.98 (s, IH), 6.81-6.72 (m, 3H), 4.99 (s, 2H), 2.82 (s, 6H).
268 δ 7.45 (s, IH), 7.23 (d, 2H), 6.92 (d, 2H), 6.55-6.48 (m, 2H), 4.92 (s, 2H), 3.82 (s, 3H).
269 δ 7.13 (d, 2H), 6.88 (s, IH), 6.75 (d, 2H), 6.44-6.38 (m, 2H), 4.94 (s, 2H), 3.77 (s, 3H), 2.77 (s,
6H).
270 δ 7.50 (s, IH), 7.25 (d, 2H), 7.04-6.95 (m, IH), 6.93-6.88 (m, 3H), 4.94 (s, 2H), 3.88 (s, 3H).
271 δ 7.11 (d, 2H), 6.86 (s, IH), 6.88-6.73 (m, 4H), 4.98 (s, 2H), 3.83 (s, 3H), 2.79 (s, 6H).
272 δ 7.48 (s, IH), 7.39 (d, 2H), 7.32-7.18 (m, 4H), 6.95 (s, IH), 6.83 (d. IH), 5.01 (s, 2H).
273 δ 7.26 (d, 2H), 7.20-7.15 (m, 4H), 6.91 (s, IH), 6.86 (s, IH), 6.73 (d, IH), 5.07 (s, 2H), 2.77 (s,
6H).
274 δ 7.44 (s, IH), 7.08 (d, 2H), 6.92 (d, 2H), 6.86-6.48 (m, 2H), 4.88 (s, 2H), 3.83 (s, 3H), 2.30 (s,
3H).
275 δ 6.97 (d, 2H), 6.87 (s, IH), 6.73 (d, 2H), 6.43-6.35 (m, 2H), 4.94 (s, 2H), 3.76 (s, 3H), 2.76 (s,
6H), 2.24 (s, 3H).
276 δ 9.71 (s, IH), 7.19-7.17 (m, 2H), 7.06 (t, J = 10.0 Hz, 2H), 6.44 (s, IH), 6.42 (s, IH), 3.78 (s,
3H).
285 δ 7.34-7.20 (m, 3H), 6.96-6.88 (m, IH), 6.80 (m, 2H), 5.00 (s, 2H).
288 δ 7.20 (d, 2H), 6.99-7.08 (m, IH), 6.93-6.80 (m, 3H), 4.99 (s, 2H), 3.88 (s, 3H).
298 δ 7.26-7.25 (m, 2 H), 7.07 (t, J = 10.0 Hz, 2H), 6.42 (s, IH), 6.39 (s, IH), 4.54 (d, J = 4.0 Hz,
2H), 4.13 (t, J= 8.0 Hz, IH), 3.77 (s, 3H).
320 δ 8.36 (d, IH), 8.15 (s, IH), 7.60 (dd, IH), 7.36 (m, IH), 6.94 (m, 2H), 6.86 (d, IH), 2.21 (2,
3H).
321 δ 8.34 (m, IH), 7.74 (d, IH), 7.29 (m, 2H), 6.84 (t, 2H), 2.17 (s, 3H).
322 δ 8.50 (d, IH), 8.45 (s, IH), 7.44 (t, IH), 7.30 (t, IH), 7.04 (dd, IH), 4.50 (s, 2H).
323 δ 8.45 (s, IH), 8.38 (d, IH), 7.42 (t, IH), 7.02 (m, 2H), 6.88 (d, IH), 2.23 (s, 3H).
330 δ 7.73 (s, IH), 7.36 (d, J = 8.0 Hz, 2H), 7.25-7.18 (m, IH), 7.10 (d, J = 8.0 Hz, 2H), 6.89-6.83
(m, IH). Cmpd. ^H NMR Data (CDCI3 solution unless indicated otherwise)81
331 δ 7.25-7.23 (m, 2H), 7.08 (t, J = 8.0 Hz, 2H), 6.43 (s, IH), 6.41 (s, IH), 5.25 (s, IH), 5.13 (s,
IH), 3.78 (s, 3H).
332 δ 7.22 (s, IH), 7.21-7.13 (m, 3H), 7.05-7.09 (t, 2H), 6.88-6.82 (t, IH).
342 δ7.75 (s, IH), 7.45-7.41 (t, J = 8.0 Hz, IH), 7.29-7.23 (m, IH), 7.01-6.98 (dd, J = 8.0 Hz,
4.0 Hz, IH,), 6.93-6.86 (m, 2H).
343 δ 7.73 (s, IH), 7.34 (d, J = 8.0 Hz, 2H), 7.23-7.20 (m, IH), 7.09 (d, J= 8.0 Hz, 2H), 7.02-6.97
(m, IH) 342 δ7.75 (s, IH), 7.45-7.41 (t, J = 8.0 Hz, IH), 7.29-7.23 (m, IH), 6.98-7.01 (dd, J= 8.0 Hz,
4.0 Hz, IH), 6.93-6.86 (m, 2 H). 347 δ 8.56 (d, IH), 7.80 (dd, IH), 7.63 (s, IH), 7.40 (t, IH), 7.10 (d, IH), 6.98 (dd, IH), 6.89 (m,
IH), 2.41 (s, 3H).
349 δ 11.0 (br s, IH), 7.42 (s, IH), 6.82-6.79 (m, 2H), 6.68 (t, J= 8.0 Hz, 2H), 6.07 (s, IH), 6.05 (s,
IH), 3.35 (s, 3H).
350 δ 7.46-7.42 (t, J= 8.0 Hz, IH), 7.24 (m, IH), 7.06-7.03 (dd, J= 8.0, 4.0 Hz, IH), 6.96-6.94 (d,
J= 8.0 Hz, IH), 6.85 (m, IH).
351 δ 7.38 (d, J= 8.0 Hz, 2H), 7.23-7.15 (m, IH), 7.13 (d, J= 8.0 Hz, 2H), 6.86-6.81 (m, IH).
352 δ 7.20-7.10 (m, 3H), 7.11-7.07 (t, J= 8.0 Hz, 2H), 6.85-6.80 (m, IH).
357 δ 8.54 (d, IH), 7.82 (dd, IH), 7.46 (t, IH), 7.21 (d, IH), 7.10 (dd, IH), 6.97 (m, IH), 4.70 (s,
2H).
363 δ 7.36-7.22 (m, IH), 7.08-6.87 (m, 4H), 6.63-6.55 (m, 2H), 2.67 (s, 6H).
374 δ 7.36 (d, J= 8.0 Hz, 2H), 7.17-7.13 (m, 3H), 6.97-6.93 (m, IH).
375 δ 7.61 (s, IH), 7.55 (t, IH), 7.36 (t, IH), 7.00 (m, 3H), 6.91 (m, IH), 2.42 (s, 3H), 2.39 (s, 3H).
376 δ 8.80 (s, IH), 7.74 (s, IH), 7.42 (t, IH), 6.98 (dd, IH), 6.90 (m, IH), 2.26 (s, 3H).
377 δ 7.72 (s, IH), 7.46 (t, IH), 7.01 (dd, IH), 6.92 (m, IH), 2.27 (s, 3H).
378 δ 7.51 (t, IH), 7.40 (t, IH), 7.08 (dd, IH), 6.96 (m, 3H), 2.39 (s, 3H), 2.33 (s, 3H).
379 δ 7.57 (t, IH), 7.44 (t, IH), 7.11 (m, 2H), 7.05 (d, IH), 7.00 (m, IH), 4.73 (s, 2H), 2.37 (s, 3H).
380 δ 8.75 (s, IH), 7.45 (t, IH), 7.03 (dd, IH), 6.93 (m, IH), 2.22 (s, 3H).
381 δ 7.50 (t, IH), 7.05 (dd, IH), 6.95 (m, IH), 2.24 (s, 3H).
382 δ 7.46-7.42 (t, J= 8.0 Hz, IH), 7.22 (m, IH), 7.06-7.03 (dd, J= 8.0, 4.0 Hz, IH), 6.97-6.94 (dd,
J= 8.0, 4.0 Hz, IH), 6.88-6.85 (m, IH).
389 δ 7.22-7.18 (m, 3H), 7.09-7.07 (t, J= 8.0 Hz, 2H), 6.84-6.79 (m, IH). 405 δ 7.19 (d, 2H), 7.06 (d, 2H), 7.04 (m, IH), 3.87 (s, 3H), 2.35 (s, 3H).
409 δ 7.74 (s, IH), 7.43-7.39 (t, J= 8.0 Hz, 3H), 7.23-7.22 (m, IH), 7.05-7.01 (m, IH), 7.00-6.97
(dd, J= 8.0, 4.0 Hz, IH), 6.92-6.89 (dd, J= 8.0, 4.0 Hz, IH).
410 δ 7.71 (s, IH), 7.20-7.16 (m, IH), 7.14 (d, J= 8.0 Hz, 2H), 7.02 (d, J= 8.0 Hz, 2H), 7.01-6.94
(m, IH), 2.34 (s, 3H).
411 δ 7.72 (s, IH), 7.26-7.15 (m, 3H), 7.02 (d, J= 8.0 Hz, 2H), 6.86-6.81 (m, IH), 2.35 (s, 3H).
412 δ 7.34 (d, J= 8.0 Hz, 2H), 7.18-7.13 (m, IH), 7.11 (d, J= 8.0 Hz, 2H), 6.82-6.77 (m, IH), 2.81 Cmpd. ^H NMR Data (CDCI3 solution unless indicated otherwise)81
(s, 3H).
413 δ 7.17-7.03 (m, 5H), 6.82-6.77 (m, IH), 2.18 (s, 3 H).
414 δ 7.32 (d, J = 8.0 Hz, 2H), 7.17-7.12 (m, IH), 7.10 (d, J = 8.0 Hz, 2H), 6.94-6.89 (m, IH), 2.13
(s, 3H).
415 δ 7.42-7.40 (t, J= 8.0 Hz, IH), 7.14-7.12 (m, IH), 6.97-6.95 (d, J= 8.0 Hz, IH), 6.89-6.87 (d, J
= 8.0 Hz, IH), 6.80 (m, IH), 2.33 (s, 3H), 2.16 (s, 3H).
416 δ 7.19 (d, J= 8.0 Hz, 2H), 7.02-6.97 (m, IH), 6.91 (d, J= 8.0 Hz, 2H), 6.67-6.63 (m, 1 H), 1.97
(s, 3H), 1.88 (s, 3H).
417 δ 7.11-7.03 (m, 5H), 6.79-6.76 (m, IH), 2.32 (s, 3H), 2.17 (s, 3H).
434 δ 8.00 (d, IH), 7.48 (t, IH), 7.34 (dd, IH), 7.03 (dd, IH), 6.95 (m, IH), 6.70 (d, IH), 3.92 (s,
3H).
437 δ 7.47 (t, IH), 7.10 (dd, IH), 7.01 (m, IH), 6.87 (s, 2H), 3.80 (s, 3H).
438 δ 7.39 (t, IH), 7.06 (d, IH), 7.02 (dd, IH), 6.92 (m, IH), 6.74 (d, IH), 3.70 (s, 3H). 450 δ 7.71 (s, 1 H), 7.15 (m, 2 H), 7.05 (m, 2 H), 6.95 (m, 1 H), 6.82 (m, 1 H), 3.85 (s, 3H). 453 δ 7.43-7.20 (m, 3H), 7.09 (d, IH), 6.42 (d, 2H), 3.78 (s, 3H).
459 δ 7.44-7.40 (t, J= 8.0 Hz, IH), 7.25-7.16 (m, IH), 7.05 (d, J= 8.0 Hz, IH), 6.97-6.95 (m, 2H).
487 δ 8.40 (m, IH), 7.85 (dd, IH), 7.61 (d, IH), 7.45 (t, IH), 7.08 (dd, IH), 6.97 (m, IH).
488 δ 8.57 (br s, IH), 7.77 (m, 2H), 6.44 (d, 2H), 3.79 (s, 3H).
460 δ 7.16 (d, J = 8.0 Hz, 2H), 7.15-7.12 (m, IH), 7.06 (d, J= 8.0 Hz, 2H), 6.93-6.92 (m, IH), 2.34
(s, 3H).
461 δ 7.17 (d, J= 8.0 Hz, 2H), 7.15-7.10 (m, IH), 7.05 (d, J= 8.0 Hz, 2H), 6.82-6.78 (m, IH), 2.36
(s, 3H).
462 δ 7.19-7.16 (m, 2H), 7.11-7.07 (t, J= 8.0 Hz, 2H), 6.67-6.63 (t, J= 8.0 Hz, 2H).
463 δ 7.45-7.40 (t, J= 8.0 Hz, IH), 7.21-7.06 (m, IH), 7.05 (d, J= 8.0 Hz, IH), 6.96-6.94 (m, 2H). 646 δ 7.16 (d, J = 8.0 Hz, 2 H,), 7.15-7.10 (m, IH), 7.06 (d, J = 8.0 Hz, 2H), 6.95-6.92 (m, IH),
2.34 (s, 3H). 465 δ 7.18 (d, J= 8.0 Hz, 2H), 7.15-7.10 (m, IH), 7.05 (d, J= 8.0 Hz, 2H), 6.81-6.78 (m, IH), 2.36
(s, 3H). 471 δ 7.35 (d, 2 H), 7.14 (d, 2 H), 6.95 (m, 1 H), 6.79 (m, 1 H), 3.83 (s, 3 H).
489 δ 7.39-7.35 (t, J= 8.0 Hz, IH), 7.12-7.08 (m, 2H), 6.95-6.91 (m, IH), 6.86-6.79 (d, J= 8.0 Hz,
IH), 2.33 (s, 3H), 2.11 (s, 3H).
490 δ 7.14-7.12 (d, J= 8.0 Hz, 2H), 7.11-7.02 (m, IH), 6.99-6.97 (d, J= 8.0 Hz, 2H), 6.77-6.72 (m,
2H), 2.34 (s, 3H), 2.16 (s, 3H).
491 δ 7.11-7.02 (m, 4 H), 6.62-6.50 (t, J= 8.0 Hz, 2H), 2.28 (s, 3H), 2.13 (s, 3H).
492 δ 7.15-7.13 (m, 2H), 7.05-7.03 (t, J= 8.0 Hz, 2H), 6.61-6.64 (t, J= 8.0 Hz, 2H), 2.15 (s, 3H).
493 δ 7.11-7.09 (d, J= 8.0 Hz, 2H), 7.14-7.01 (m, IH), 6.99-6.97 (d, J= 8.0 Hz, 2H), 6.88-6.83 (m,
IH), 2.32 (s, 3H), 2.12 (s, 3H).
494 δ 7.40-7.36 (t, J= 8.0 Hz, IH), 7.19 (m, 2H), 7.01 (d, J= 8.0 Hz, IH), 6.98-6.90 (m, 2H), 2.13 Cmpd. ^H NMR Data (CDCI3 solution unless indicated otherwise)81
(s, 3H).
495 δ 7.12 (d, J = 8.0 Hz, 2H), 7.10-7.05 (m, IH), 7.03 (d, J = 8.0 Hz, 2H), 6.91-6.87 (m, IH), 2.33
(s, 3H), 2.13 (s, 3H).
505 δ 7.15 (d, J = 8.0 Hz, 2H), 7.13-7.05 (m, IH), 7.03 (d, J= 8.0 Hz, 2H), 6.80-6.75 (m, IH), 2.35
(s, 3H), 2.17 (s, 3H).
506 δ 7.68 (s, IH), 7.15 (d, J= 8.0 Hz, 2H), 7.03 (d, J= 8.0 Hz, 2H), 6.43 (d, J= 12.0 Hz, 2H), 3.78
(s, 3H), 2.35 (s, 3H).
507 δ 7.70 (s, IH), 7.14 (d, J= 8.0 Hz, 2H), 7.01 (d, J= 8.0 Hz, 2H), 6.69-6.65 (t, J= 8.0 Hz, 2H),
2.38 (s, 3H).
508 δ 7.71 (s, IH), 7.24-7.13 (m, 3H), 7.07-7.03 (t, J= 8.0 Hz, IH), 6.98-6.96 (m, IH). 510 δ 7.35 (d, 2 H), 7.14 (d, 2 H), 6.95 (m, 1 H), 6.80 (m, 1 H), 3.84 (s, 3 H).
514 δ 7.46 (d, IH), 6.96 (d, IH), 6.41 (m, 2H), 3.85 (s, 3H), 3.78 (s, 3H).
521 δ 7.12 (d, J= 8.0 Hz, 2H), 6.98 (d, J= 8.0 Hz, 2H), 6.36 (d, J= 8.0 Hz, 2H), 3.74 (s, 3H), 2.27
(s, 3H), 2.13 (s, 3H).
522 δ 7.11-7.00 (m, 4H), 6.37 (d, J= 8.0 Hz, 2H), 3.75 (s, 3H), 2.28 (s, 3H), 2.13 (s, 3H).
523 δ 7.19-7.17 (m, 2H), 7.05-7.09 (t, J= 8.0 Hz, 2H), 6.40 (d, J= 8.0 Hz, 2H), 3.71 (s, 3H).
524 δ 7.16 (d, J= 8.0 Hz, 2H,), 7.05 (d, J= 8.0 Hz, 2H), 6.39 (d, J= 8.0 Hz, 2H), 3.76 (s, 3H), 2.36
(s, 3H).
574 δ 7.41 (t, IH), 7.11 (dd, IH), 7.01 (m, IH), 6.86 (s, 2H), 3.80 (s, 3H).
575 δ 7.42 (t, IH), 7.01 (m, 2H), 6.90 (m, 2H), 3.75 (s, 3H).
576 δ 8.46 (m, IH), 7.73 (m, IH), 7.39 (m, IH), 6.48 (m, IH), 6.34 (m, IH), 3.77 (s, 3H).
577 δ 8.25 (s, IH), 7.59 (d, IH), 7.32 (m, IH), 7.19 (d, IH), 6.86 (t, 2H), 2.36 (s, 3H). 581 δ 7.15-7.10 (m, 4H), 6.53-6.47 (m, 2H), 4.54 (s, 2H), 3.80 (s, 3H), 2.33 (s, 3H).
592 δ 8.24 (s, IH), 7.54 (d, IH), 7.39 (m, 2H), 6.91 (t, 2H).
593 δ 8.39 (s, 2H), 7.46 (t, IH), 7.07 (dd, IH), 6.94 (d, IH).
594 δ 8.42 (s, 2H), 7.76 (s, IH), 7.45 (t, IH), 7.01 (dd, IH), 6.90 (d, IH).
616 δ 8.20 (dd, IH), 7.54 (m, IH), 7.31 (m, IH), 6.93 (m, 2H), 6.81 (t, IH), 3.81 (s, 3H).
672 δ 7.35 (d, 2H), 7.04 (d, 2H), 6.40 (m, 2H), 6.50 (m, IH), 3.75 (s, 3H), 2.32 (s, 3H).
686 δ 7.35-7.29 (m, IH), 7.08-6.92 (m, 3H), 6.56-6.50 (m, 2H), 4.54 (s, 2H), 3.82 (s, 3H).
712 δ 7.36-7.28 (m, IH), 7.08-7.02 (m, 2H), 6.98-6.92 (m, IH), 6.53 (d, 2H), 4.54 (s, 2H), 3.82 (s,
3H).
BIOLOGICAL EXAMPLES OF THE INVENTION
General protocol for preparing test suspensions for Tests A-J: The test compounds were first dissolved in acetone in an amount equal to 3% of the final volume and then suspended at the desired concentration (in ppm) in acetone and purified water (50/50 mix) containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in tests A-J. Spraying a 200 ppm test suspension to the point of run-off on the test plants was the equivalent of a rate of 500 g/ha. (An asterisk "*" next to the rating value indicates a 40 ppm test suspension.)
TEST A
Grape seedlings were inoculated with a spore suspension of Plasmopara viticola (the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20 0C for 24 h. After a short drying period, the grape seedlings were sprayed with the test suspension to the point of run-off and then moved to a growth chamber at 20 0C for 5 days, after which time the grape seedlings were placed back into a saturated atmosphere at 20 0C for 24 h. Upon removal, visual disease ratings were made. TEST B
The test suspension was sprayed to the point of run-off on bentgrass (Agrostis sp.) seedlings. The following day the seedlings were inoculated with a bran and mycelial slurry of Rhizoctonia solani (the causal agent of turf brown patch) and incubated in a saturated atmosphere at 27 0C for 48 h, and then moved to a growth chamber at 27 0C for 6 days, after which time visual disease ratings were made.
TEST C
The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Botrytis cinerea (the causal agent of tomato Botrytis) and incubated in saturated atmosphere at 20 0C for 48 h, and then moved to a growth chamber at 24 0C for 3 days, after which time visual disease ratings were made.
TEST D
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Alternaria solani (the causal agent of tomato early blight) and incubated in a saturated atmosphere at 27 0C for
48 h, and then moved to a growth chamber at 20 0C for 5 days, after which time visual disease ratings were made.
TEST E
The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of tomato late blight) and incubated in a saturated atmosphere at
20 0C for 24 h, and then moved to a growth chamber at 20 0C for 5 days, after which time visual disease ratings were made.
TEST F The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Septoria nodorum (the causal agent of wheat glume blotch) and incubated in a saturated atmosphere at 24 0C for 48 h, and then moved to a growth chamber at 20 0C for 9 days, after which time visual disease ratings were made.
TEST G The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Septoria tritici (the causal agent of wheat leaf blotch) and incubated in saturated atmosphere at 24 0C for 48 h, and then moved to a growth chamber at 20 0C for 19 days, after which time visual disease ratings were made. TEST H
Wheat seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20 0C for 24 h, and then moved to a growth chamber at 20 0C for 2 days. At the end of this time the test suspension was sprayed to the point of run-off on the wheat seedlings, then the seedlings were moved to a growth chamber at 20 0C for 4 days, after which time visual disease ratings were made.
TEST I
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at
20 0C for 24 h, and then moved to a growth chamber at 20 0C for 6 days, after which time visual disease ratings were made
TEST J
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore dust of Erysiphe graminis f. sp. tritici, (the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20 0C for 7 days, after which time visual disease ratings were made.
Results for Tests A-J are given in Table A. In the Table, a rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control (relative to the controls). A dash (-) indicates no test results. All results are for 200 ppm except where followed by "*", which indicates 40 ppm.
TABLE A
Cmpd. Test A Test B Test C Test D Test E TTeesstt FF TTeesstt GG Test H Test I Test J
- 99* 94* 0* 93* 16* 99*
65 99 100 100 100 100 100
99 99 100 99 100 99 100 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
4 0 18 67 0 0 0 93 79 94
5 0 38 98 99 0 0 100 88 99
6 0 99 99 100 0 95 100 100 100
7 0 81 100 100 0 0 99 98 99
8 - - 99 8 - 0 68 74 97
9 - - 97* 100* - 0* 33* 68* 94*
10 - - 99* 99* - 0* 94* 97* 100*
11 6 99 100 100 0 99 99 100 100
12 - - 87* 100* - 94* 96* 99* 100*
13 - - 0 - 0 97 99 90
14 - - 99 - 0 53 96 75
15 - - 98* 100* - 0* 84* 97* 95*
16 - - 97 8 - 92 3 41 0
17 - - 100 - 0 96 98 100
18 - - 98 99 - 0 93 98 100
19 - - 99 99 - 0 88 100 95
20 0 0 100 100 0 0 100 98 100
21 13 100 99 100 0 100 100 99 100
22 - - 93 100 - 0 91 100 100
23 - - 99 100 - - 88 100 99
24 - - 90 0 - 0 67 28 95
25 - - 93 0 - 0 0 6 13
26 - - 96 8 - 0 0 34 0
27 - - 97 100 - 51 95 100 100
28 - - 99 100 - 74 91 100 100
29 - - 99* 100* - 0* 94* 100* 100*
30 - - 99 0 - 0 73 0 95
31 - - 92 15 - 0 27 13 73
32 - - 99 100 - 100 95 100 100
33 - - 99 100 - 0 93 99 98
34 - - 99* 100* - 99* 90* 91* 100* 100*
35 20 100 100 100 0 100 100 100 100
36 - - 99 100 - 99 92 100 100
37 - - 99* 100* - 100* 92* 100* 100*
38 - - 99* 100* - 0* 96* 86* 87*
39 - - 94* 100* - 0 89* 89* 96*
40 99* 100* 99* 95* 98* 100* Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
41 99 100 64 94 99 98 42 99* 100* 99* 93* 91* 100* 43 98* 100* 97* 96* 97* 99* 44 99* 100* 40* 92* 99* 98* 45 100 98 100 99 100 100 46 86* 97* 0* 83* 26* 78* 47 94 42 0 77 54 93 48 99 100 100 94 100 100 49 98 100 100 94 99 99 50 98 100 100 92 100 100 51 94 100 100 94 97 99 52 84 100 0 97 99 100 53 89 100 0 95 100 99 54 92 24 0 87 99 91 55 94* 100* 98* 93* 99* 100* 56 96* 100* 60* 96* 94* 99 57 84 99 0 87 96 100 58 98 100 51 79 99 100 59 93* 100* 82* 97* 86* 97* 60 81 0 0 2 0 0 61 40 0 0 60 92 99 62 94 0 0 5 0 81 63 0 0 0 33 41 100 64 99 100 95 95 100 96 65 0 100 0 95 41 95 66 99 100 99 94 99 99 67 98 44 99 0 80 0 99 68 0 0 0 40 9 99 69 74 99 0 25 0 97 70 71 0 0 0 0 0 71 47 33 0 2 9 56 72 96 100 92 97 99 100 73 100 100 60 87 100 100 74 98 96 31 98 99 99 75 98 93 0 95 77 98 76 37 99 60 97 99 100 77 98 100 82 97 99 100 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
78 91 100 0 92 99 100 79 53 97 0 95 92 100 80 90 100 100 98 100 100 81 81 100 69 93 98 100 82 90 100 100 91 99 100 83 97 100 99 98 100 100 84 0 99 0 88 91 99 85 73 100 11 98 96 100 86 0 0 0 93 27 99 87 0 0 0 84 27 99
75 0 0 0 68 99
89 0 0 0 3 85 98
90 0 0 0 0 54 0
91 98 100 100 99 96 100
92 76 100 0 98 89 100
93 97 100 100 99 98 100
94 56 53 0 95 99 100
95 96 97 95 95 100 100
96 98* 100* 97* 97* 97* 99*
97 94 97 0 95 91 99
98 0* 0* 0* 27* 0* 0*
99 0 0 0 25 91 0
100 97 93 99 97 98 99
101 88 0 0 97 100 99
102 98 0 55 97 99 99
103 79 92 90 98 100 99
104 92 98 0 32 0 95
105 98 99 94 94 99 100
106 100 99 64 93 99 95
107 96 100 100 96 100 100
108 100* 100* 0* 74* 98* 99*
109 94 57 0 94 68 63
110 94 99 100 95 97 96
111 81 99 99 100 100 89 99
112 99 100 89 98 99 99
113 98 99 97 95 97 97
114 93 0 0 95 41 72 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
115 99 99 99 0 98 99 98 100 116 0* 0* 0* 0* 0* 0* 117 96 100 99 97 99 100 118 99 100 60 94 99 100 119 96 80 40 91 80 0 120 98 0 0 96 90 92 121 99 100 0 85 89 97 122 98 100 100 96 100 100 123 99 99 0 48 90 94 124 98 97 0 90 95 98 125 98 100 0 92 91 100 126 97 99 69 96 99 99 127 99 100 98 95 100 100 128 97 96 96 93 97 100 129 99 100 0 89 74 95 130 98 100 0 85 99 96 131 90* 99* 0* 85* 0* 48* 132 94 98 0 92 74 97 133 0 0 0 0 0 0 134 97 100 99 93 99 100 135 99 100 0 93 100 100 136 99 100 99 96 100 100 137 94 100 0 98 55 97 138 98 100 92 99 100 100 139 99 100 0 75 98 98 140 0 0 0 93 55 39 141 99 100 0 91 99 100 142 99 100 97 94 100 100 143 99 100 100 100 100 100 144 100 100 100 100 100 100 145 99 100 100 100 100 100 146 99 100 100 100 100 100 147 91 100 82 100 100 99 148 99 100 99 100 100 100 149 53 0 98 96 95 95 150 99 100 60 98 97 100 151 97* 100* 69* 99* 89* 96* Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
152 - - 99 99 69 96 89 99
153 - - 98 100 69 96 99 100
154 - - 99 100 0 93 86 99
155 - - 99 100 87 95 99 100
156 - - 98* 100* 99* 97* 97* 99*
157 - - 97 99 98 97 100 100
158 - - 99 100 96 97 100 100
159 - - 99 100 99 97 100 100
160 - - 91 93 0 93 28 98
161 - - 99 71 0 1 80 100
162 - - 88* 97* 0* 93* 23* 94*
163 - - 0* 0* 0* 10* 0* 0*
164 - - 91* 88* 0* 96* 19* 94*
165 - - 0 0 0 93 27 93
166 - - 96 97 40 96 91 100
167 - - 99* 100* 0* 95* 0* 98*
168 - - 97 99 84 98 100 100
169 - - 99 100 40 96 88 99
170 - - 97 98 0 95 99 99
171 - - 99 100 100 98 98 99
172 - - 99 99 100 98 99 99
173 - - 98* 0* 0* 90* 41* 0*
174 - - 98 99 82 98 100 100
175 - - 97 97 82 98 100 99
176 - - 96 91 0 87 99 99
177 - - 88 0 0 79 99 99
178 9 0 99 99 0 100 74 100
179 0 0 99 9 0 98 99 99
180 0 88 99 99 0 98 99 100
181 - 24 99 0 0 94 98 99
182 - - 99 100 73 96 97 99
183 - - 99* 91* 0* 85* 66* 48*
184 - - 99 100 0 97 100 100
185 - - 99 100 78 94 100 99
186 - - 98 88 0 97 100 100
187 - - 99 100 94 97 100 100
188 98 100 0 97 100 99 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
189 98 100 51 97 100 99
190 97 100 0 93 100 100
191 0 0 99 26 29 0 97 80 93
192 0 21 99 16 0 0 94 84 99
193 99 100 0 98 97 98
194 99 95 73 97 100 96
195 99 100 64 94 100 94
196 99 100 0 92 100 97
197 99 99 0 93 100 100
198 98 99 0 90 100 95
199 92 100 100 96 98 95
200 0 0 0 45 0 21
201 99 100 100 98 96 100
202 91 61 98 97 98 100
203 87 98 87 97 100 99
204 90* 91* 0* 90* 18* 26*
205 99 100 100 98 100 100
206 95 99 0 98 100 99
207 93 99 80 98 100 99
208 92 39 0 98 98 99
209 88 99 0 96 99 99
210 97 66 0 91 98 99
211 74 0 0 0 37 86
212 40* 20* 0* 0* 0* 0*
213 63 0 0 96 100 42
214 100* 99* 97* 94* 97* 98*
215 98 85 0 96 68 91
216 99* 100* 0* 96* 93* 94*
217 33* 57* 0* 13* 0* 0*
218 99* 99* 0* 91* 80* 73*
219 98 97 51 96 99 99
220 98 99 0 97 99 100
221 99 99 0 95 97 98
222 99 99 0 99 97 98
223 99 100 60 98 99 100
224 93 51 0 90 80 98
225 96 100 0 98 99 100 Cmpd. Test A Test B Teesstt CC Test D Test E Test F Test G Test H Test I Test J
226 76 67 0 88 0 95 227 98 96 0 94 99 99 228 96 99 0 98 94 99 229 98 99 0 98 89 91 230 99 97 0 99 94 99 231 87 61 100 99 96 98 232 0 0 0 95 9 0 233 96* 88* 0* 95* 41* 94* 234 95 99 0 98 55 98 235 99 99 92 99 97 99 236 100 100 99 96 100 100 237 100 100 100 98 100 100 238 99 99 0 93 96 100 239 100 100 100 96 99 100 240 100 100 100 97 100 100 241 100 100 100 96 96 93 242 99* 95* 51* 95* 89* 92* 243 99 100 98 99 100 98 244 100 100 99 96 99 100 245 100 99 100 97 95 99 246 100 100 95 93 100 99 247 100 100 100 97 100 100 248 99* 47* 0* 92* 68* 92* 249 100* 99* 73* 93* 74* 81* 250 99 100 0 83 99 94 251 99 0 0 81 9 0 252 15 0 0 13 0 0 253 94 0 0 91 74 0 254 100 100 0 95 99 98 255 99 0 0 95 86 91 256 100 100 100 97 100 99 257 100 100 99 95 100 100 258 99 0 42 87 97 78 259 99 16 0 63 82 93 260 100 95 0 92 94 99 261 99 100 100 95 100 100 262 99 99 69 96 100 100 Cmpd. Test A Test B Teesstt CC Test D Test E Test F Test G Test H Test I Test J
263 99 100 100 95 - 100 100 264 99 88 0 95 - 98 99 265 97 0 60 86 32 61 0 266 100 100 97 94 98 99 99 267 98 0 0 91 9 86 97 268 99 100 98 87 63 99 75 269 100 0 87 83 9 9 0 270 100 100 98 86 0 99 96 271 99 9 0 82 0 83 0 272 64 0 0 91 17 55 0 273 63 0 0 13 46 41 0 274 100 100 51 94 48 99 77 275 100 82 0 85 9 74 0 276 100 100 0 92 9 98 100 277 99* 0* 0* 89* - 88* 94* 278 99 100 100 95 - 100 100 279 100 100 100 93 - 100 100 280 100 100 100 95 - 100 100 281 100 100 97 96 - 100 100 282 99 99 0 93 65 99 100 283 100 98 0 93 0 93 99 284 100 99 92 95 6 99 100 285 99 85 83 94 98 100 100 286 99 96 79 95 64 99 100 287 100 100 99 95 17 100 99 288 100 91 73 94 32 96 99 289 100 96 0 94 11 94 97 290 95 0 0 85 11 19 0 291 99 80 0 94 6 98 94 292 99 98 69 93 11 99 99 293 99 91 0 95 6 99 100 294 99 100 98 96 11 98 97 295 99 0 0 94 0 80 0 296 100 96 86 96 17 99 97 297 99* 100* 99* 94* - 99* 100* 298 100 100 0 96 0 98 0 299 99 99 90 97 0 99 99 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
300 99 98 0 91 48 97 99 301 100 94 0 95 6 91 96 302 100 100 0 94 17 98 100 303 100* 99* 98* 96* 0* 74* 81* 304 0* O* 0* 27* 0* 0* 0* 305 63* O* 0* 23* 11* 0* 0* 306 99 96 0 94 6 91 99 307 100 99 0 97 11 97 99 308 99* 100* 0* 88* 11* 41* 0* 309 100 100 100 97 11 100 100 310 99 100 99 96 61 100 100 311 n 9oo 9 0 - 100 99 95 312 99 82 0 - 9 99 92 313 99 100 0 - 95 100 99 314 99 100 100 93 32 100 100 315 99 100 100 95 86 100 100 316 99 99 95 93 6 99 100 317 100 100 100 95 17 99 100 318 100 16 0 91 0 9 87 319 99 24 0 98 6 28 81 320 99 67 0 100 0 28 99 321 100 100 100 100 83 100 100 322 62* 0* 0* 0* 63* 28* 0* 323 100 99 0 100 70 100 99 324 99 99 82 93 9 97 99 325 94 91 51 96 0 97 99 326 100 100 51 96 67 98 100 327 99* 98* 0* 94* 0* 86* 0* 328 100 98 0 95 9 94 98 329 99 99 0 94 0 90 99 330 100 100 0 96 9 98 99 331 100 100 99 95 85 100 100 332 100 99 60 95 9 96 99 333 100* 100* 99* 91* 0* 100* 100* 334 100* 100* 90* 93* 0* 100* 100* 335 100* 100* 82* 91* 0* 99* 99* 336 99* 88* 99* 96* 0* 74* 87* Cmpd. Test A Test B Teesstt CC Test D Test E Test F Test G Test H Test I Test J
337 19* 0* 0* 23* 0* 0* 0* 338 100 100 80 93 0 99 99 339 100 99 78 95 0 96 96 340 99 98 0 92 0 94 95 341 91* 24* 0* 0* Q* 0* 0* 342 100 99 0 95 0 98 99 343 100 97 64 94 0 93 98 344 100 0 0 95 17 89 99 345 64 0 0 27 0 0 0 346 99 0 0 38 9 9 0 347 93 0 0 70 26 9 0 348 0 0 0 8 0 0 27 349 100 99 99 88 0 99 95 350 99 100 82 91 0 99 100 351 100 100 99 93 54 100 100 352 100 100 87 92 18 97 77 353 0 0 0 8 0 41 0 354 100 99 0 93 0 98 97 355 0 0 0 i 0 28 0 356 98 57 0 72 17 0 0 357 63 0 100 50 0 55 0 358 99 0 0 90 0 41 0 359 98 0 0 35 0 80 0 360 100 99 0 95 9 99 98 361 99 0 0 93 9 74 80 362 100 99 0 86 0 83 49 363 99 0 0 53 9 0 0 364 100 100 0 58 0 98 83 365 100 100 40 91 54 99 96 366 100 100 64 91 41 99 97 367 99 100 89 90 9 98 97 368 99 100 0 92 0 99 96 369 99 100 98 92 74 99 99 370 99 100 87 89 100 100 100 371 31* 0* 0* 48* 0* 0* 0* 372 99 0 0 91 0 74 0 373 99* 98* 60* 92* 0* 95* 99* Cmpd. Test A Test B Teesstt CC Test D Test E Test F Test G Test H Test I Test J 374 99 99 0 94 0 90 98 375 99 26 0 92 32 68 62 376 90 0 0 78 0 54 67 377 0 0 0 3 0 27 33 378 100 0 0 93 0 74 75 379 99 0 0 86 0 27 0 380 100 91 0 91 0 99 99 381 94 0 0 78 0 0 0 382 100* 99* 0* 96* 0* 95* 97* 383 100* 99* 35* 96* 0* 91* 98* 384 100* 99* 0* 95* 0* 67* 95* 385 99* 99* 0* 95* 0* 95* 99* 386 99 100 0 96 0 98 95 387 0 0 0 0 0 0 0 388 99 100 60 99 - 100 100 389 98 100 0 91 99 98 390 100 100 99 95 18 100 100 391 100 99 0 94 0 99 100 392 100 100 100 97 60 99 100 393 99 100 99 95 79 99 100 394 3* 0* 0* 28* 0* 45* 0* 395 30 0 0 67 0 0 0 396 100* 100* 99* 93* 0* 100* 99* 397 100* 98* 0* 94* 0* 88* 13* 398 100 80 79 96 0 79 100 399 100 99 82 96 0 82 100 400 100 100 99 94 0 99 100 401 99 100 0 96 0 73 100 402 100 100 99 96 0 94 99 403 99 0 0 97 0 77 86 404 100 0 0 99 0 97 98 405 99 98 0 100 0 98 99 406 100 100 100 93 100 100 100 407 100 0 92 96 0 97 98 408 0* 0* 0* 3* 0* 0* 0* 409 100 9 0 100 0 96 98 410 98 99 0 100 0 99 100 Cmpd. Test A Test B T^eesstt CC Test D Test E Test F Test G Test H Test I Test J
411 100 100 0 99 0 99 100 412 100* 100* 0* 99* 0* 74* 99* 413 100* 99* 0* 14* Q* 0* 0* 414 99* 99* 0* 96* 0* 93* 100* 415 100* 100* 0* 99* 0* 94* 98* 416 100* 100* 0* 97* 0* 26* 99* 417 100* 99* 0* 89* Q* Q* 94* 418 100 100 99 100 0 97 100 419 100 100 100 100 0 97 99 420 100 100 99 100 0 100 100 421 100 98 0 100 0 100 100 422 100 100 60 100 0 99 100 423 100* 0* 69* 94* 0* 91* 99* 424 100 100 99 100 0 94 100 425 100 100 100 100 0 96 100 426 100 100 100 100 27 100 100 427 100 100 99 100 0 93 100 428 100 100 0 99 0 100 100 429 99 77 0 99 0 98 98 430 100 100 100 100 0 100 100 431 9 9 0 98 9 0 0 432 33 0 0 25 0 0 0 433 50 0 0 92 0 0 0 434 96 9 0 99 0 68 76 435 99 24 0 99 0 68 0 436 87 98 0 81 0 0 0 437 99 80 60 100 0 98 98 438 0 0 0 86* 0 0 0 439 97 100 95 94 - 100 100 440 99 100 98 95 - 98 99 441 97 99 0 97 - 97 99 442 99 99 0 95 - 99 100 443 99 99 99 97 - 89 100 444 99 100 100 98 - 95 99 445 97* 100* 92* 95 - 97* 98* 446 96* 100* 0* 95* - 68* 91* 447 94 80 0 30 0 81 Cmpd. Test A Test B Teesstt CC Test D Test E Test F Test G Test H Test I Test J
448 97 100 89 98 - 95 98 449 99 100 99 97 - 99 100 450 97 100 99 97 - 100 100 451 0 0 0 82 - 19 0 452 55 0 0 86 - 86 76 453 99 100 90* 93 - 100 100 454 77 100 33 93 - 100 100 455 99 95 0 95 - 99 68 456 0 0 0 88 - 0 43 457 85 0 0 91 - 97 97 458 96 16 0 92 - 95 89 459 99* 63* 0* 95* 9* 98* 98* 460 99* 85* 0* 97* 0* 93* 96* 461 99* 99* 0* 94* 0* 97* 98* 462 100* 100* 0* 96* 0* 78* 99* 463 99* 99* 0* 95* 0* 100* 99* 464 99* 89* 0* 72* 0* 99* 100* 465 100* 99* 0* 88* 0* 99* 99* 466 99* 100* 0* 82* 0* 93* 100* 467 94* 0* 0* 32* 0* 71* 96* 468 99* 99* 0* 96* 0* 91* 58* 469 65* 0* 0* 79* 0* 81* 0* 470 99* 99* 0* 92* 0* 99* 87* 471 100 100 100 97 0 98 100 472 100 100 100 96 80 100 100 473 99 100 0 97 0 100 100 474 99 57 0 90 0 36 95 475 98 26 0 92 0 87 42 476 0 0 0 59 0 78 47 477 9 0 0 0 0 75 0 478 100 93 0 93 0 96 97 479 100 100 95 94 0 99 100 480 100 100 95 96 0 99 100 481 100 100 99 95 0 97 100 482 99 99 69 95 0 91 99 483 100 99 0 94 32 98 100 484 100 100 89 95 28 100 100 Cmpd. Test A Test B Teesstt CC Test D Test E Test F Test G Test H Test I Test J
485 96 88 0 95 0 98 98 486 66 0 0 0 0 14 0 487 96 0 0 88 0 78 0 488 99 100 100 93 41 100 100 489 96* 98* 0* 93* 0* 100* 100* 490 97* 99* 0* 87* 0* 76* 100* 491 92* 99* 0* 91* 0* 0* 0* 492 94* 100* 0* 82* 0* 0* 0* 493 96* 99* 0* 93* 0* 97* 99* 494 89* 99* 0* 89* 0* 99* 99* 495 97* 99* 0* 31* 0* 99* 100* 496 93* 99* 0* 6* 0* 0* 97* 497 97 99 100 97 0 100 100 498 99 100 95 95 0 100 100 499 99 100 100 93 100 100 100 500 98 100 100 94 98 100 100 501 98 99 98 95 0 67 99 502 90* 92* 60* 93* 0* 98* 100* 503 99 99 99 96 0 100 100 504 99 100 100 97 0 99 100 505 99 100 98 97 78 100 100 506 100 100 92 99 78 100 99 507 100 95 0 88 0 100 98 508 100 100 0 94 78 99 99 509 98 77 0 92 9 85 78 510 99 100 100 99 9 98 100 511 99 99 99 99 0 99 100 512 97 98 0 98 40 79 99 513 99 100 100 100 100 100 100 514 99 99 73 100 0 93 99 515 97 99 0 100 100 100 100 516 97 100 100 100 100 100 100 517 100 100 96 98 0 99 100 518 100 99 99 98 0 98 100 519 100 100 100 97 0 100 100 520 100 100 0 97 0 99 100 521 99* 99* 0* 98* 0* 98* 90* Cmpd. Test A Test B Teesstt CC Test D Test E Test F Test G Test H Test I Test J
522 100* 100* 0* 98* 0* 99* 96* 523 100* 100* 0* 98* 0* 99* 97* 524 99* 100* 60* 98* 85* 99* 97 525 100* 100* 80* 98* 68* 100* 98* 526 100 100 100 99 0 100 100 527 100 99 0 95 37 91 88 528 100 100 99 99 15 96 100 529 0 0 0 82 9 48 0 530 0 0 0 58 0 88 71 531 100 0 0 99 41 99 95 532 97 0 0 99 0 99 91 533 0 0 0 49 15 92 82 534 38 0 0 2 0 0 0 535 0 0 0 2 0 0 0 536 89 68 0 90 37 98 98 537 99 76 60 97 9 100 99 538 99 0 0 99 27 100 100 539 36 0 0 7 0 93 95 540 15 0 0 i 0 0 21 541 0 0 0 0 0 0 0 542 99* 96* 0* 97* 0* 98* 89* 543 99* 60* 0* 97* 0* 95* 0* 544 84 98 0 82 9 91 86 545 100 100 98 99 27 100 99 546 100 100 99 98 0 100 100 547 99 88 60 97 0 99 100 548 98 100 94 96 0 99 100 549 100 100 99 98 0 100 100 550 100 100 100 97 0 99 100 551 100 100 96 98 0 100 100 552 99 100 0 96 0 46 98 553 100 100 100 99 100 100 100 554 100 100 100 99 100 100 100 555 100 99 69 98 0 100 98 556 100 99 98 95 87 100 97 557 100 99 78 96 43 99 87 558 100 0 0 94 15 99 100 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
559 94 41 0 95 29 88 98
560 99* 0* 0* 65* 33* 79* 93*
561 99 100 97 100 9 100 100
562 100 100 99 100 0 99 100
563 100 100 100 100 0 94 100
564 99* 100* 64* 99* 66* 100* 100*
565 100 100 100 96 97 100 100
566 100 100 100 97 97 100 100
567 99 67 0 94 7 99 100
568 99 100 98 94 72 100 100
569 100 100 100 97 84 100 99
570 0 0 0 97 0 13 69
571 33 0 0 82 0 90 0
572 100* 99* 92* 95* 0* 99* 71*
573 100 100 0 96 22 100 99
574 100 0 60 100 0 98 97
575 96 0 0 73 0 76 72
576 100 99 100 100 100 100 99
577 100 100 87 100 97 100 100
578 0 58 98 37 0 0 100 - 74 98
579 0 92 99 97 0 0 100 - 93 100
580 0 88 98 0 0 0 100 - 84 90
581 99* 33* 0* 96* 84* 98* 21*
582 100 100 99 97 15 99 100
583 99 97 0 94 0 85 83
584 99 99 0 98 0 100 99
585 100 99 0 100 0 100 99
586 0 0 0 3 0 0 21
587 25 80 0 97 7 0 97
588 100 100 100 97 100 100 100
589 100 99 98 98 97 100 100
590 100* 100* 94* 96* 7* 100* 100*
591 100 100 0 97 96 98 98
592 100 100 100 96 100 100 100
593 100 100 99 96 99 100 100
594 100 99 0 94 78 99 100
595 100 80 0 96 22 74 98 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
596 94 73 0 98 0 74 97
597 100 100 97 98 99 100
598 100 100 100 99 99 100 100
599 26 0 0 9 0 0 0
600 86 100 0 94 7 0 99
601 99* 98* 87* 99* 7* 97* 97*
602 99* 91* 0* 99* 0* 98* 81*
603 99 100 99 99 98 100 100
604 99 100 100 99 97 100 100
605 19 0 0 73 0 0 94
606 99 100 0 99 0 28 100
607 100* 96* 31* 99* 7* 86* 82*
608 17* 0* 0* 4* 7* 41* 0*
609 99 100 100 99 100 100 100
610 99 100 99 99 100 100 100
611 91 66 0 81 0 16 57
612 99 100 60 96 0 8 100
613 99* 100* 64* 99* 15* 97* 21*
614 89* 0* 0* 92* 0* 28* 0*
615 100 100 0 100 0 99 100
616 100 0 0 99 0 98 99
617 99 99 0 100 100 100 99
618 98 85 0 98 99 99 97
619 99 53 0 96 51 98 99
620 100 99 90 98 100 100 99
621 100 100 99 98 100 100 100
622 100 100 99 99 100 100 100
623 98 33 0 97 0 98 100
624 99 64 0 94 0 99 90
625 98 0 0 97 0 0 94
626 99 99 0 100 17 79 97
627 99 99 0 99 40 95 98
628 99 100 0 100 0 99 99
629 0 0 0 0 0 0 0 - 0 0
630 0 0 0 0 0 69 0 - 95 0
631 99 99 0 100 40 99 100
632 99 100 0 98 99 100 97 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
633 - 0* 0* - 0* 0* 0* 44* 0*
634 - 0* 0* - 0* 0* 0* 0* 0*
635 - 99* 0* - 0* 81* 0* 39* 0*
636 - 90* 24* - 0* 95* 0* 52* 0*
637 - 97* 0* - 0* 92* 0* 65* 0*
638 - 99 99 - 55 99 0 95 56
639 0 0 0 0 0 0 0 - 0 0
640 0 0 0 0 0 0 0 - 0 0
641 - 95 96 - 94 99 100 100 83
642 - 97* 0* - 0* 94* 0* 98* 56*
643 - 0* 0* - 0* 87* 0* 52* 0*
644 0 94 0 0 0 0 - 0 0
645 - 99* 17* - 0* 95* 0* 83* 35*
646 - 93* 47* - 0* 97* 0* 92* 35*
647 - 0* 0* - 0* 95 0* 0* 69*
648 9 0 0 0 0 0 0 - 0 0
649 - 0* 0* - 0* 97* 0* 61* 0*
650 - 0* 0* - 0* 0* 9* 0* 0*
651 - 97 0 - 60 97 0 95 79
652 - 0* 0* - 0* 0* 6* 0* 0*
653 - 99* 99* - 78* 100* 99* 100* 99*
654 - 100* 99* - 91* 98* 100* 99* 100*
655 - 8* 0* - 0* 97* 49* Q* 0*
656 - 100 100 - 20 99 9 100 100
657 - 99* 99* - 99* 99* 100* 100* 96*
658 - 0 0 - 0 55 0 61 61
659 - - - - - - - - -
660 - 100 98 - 82 100 9 92 100
661 - 99 99 - 87 99 0 100 100
662 - 100 99 - 100 99 0 98 100
663 - 100 99 - 99 99 54 99 100
664 - 100 99 - 96 99 46 97 100
665 - 100 99 - 99 99 54 99 100
666 - 100 100 - 99 99 100 100 100
667 - 100 100 - 100 99 8 97 76
668 - 100 99 - 91 99 0 85 96
669 100 100 99 99 73 98 0 Cmpd. Test A Test B Teesstt CC Test D Test E Test F Test G Test H Test I Test J 670 100 100 100 98 0 98 94 671 99 100 92 95 17 78 0 672 96 0 0 87 0 0 0 673 99 100 99 99 9 100 90 674 99 93 98 99 98 100 94 675 100 100 99 98 100 100 100 676 100 99 99 99 99 100 98 677 100 100 100 99 100 100 100 678 100 100 100 99 100 100 100 679 100 100 99 99 18 100 100 680 99 100 98 100 0 100 100 681 99 100 98 99 0 99 100 682 100 100 99 100 97 100 100 683 100* 97* 0* 67* 8* 0* 98* 684 100 100 100 99 53 99 100 685 100* 99* 0* 87* 0* 68* 64* 686 100* 100* 82* 98* 98* 99* 98* 687 100* 100* 99* 98* 100* 100* 100* 688 100* 33* 0* 97* 8* 0* 78* 689 0 0 0 0 0 0 0 690 78 0 0 98 0 74 81 691 99* 99* 51* 95* 39* 82* 64* 692 100 70 0 99 8 0 79 693 100 100 99 99 100 100 100 694 100* 100* 99* 98* 0* 99* 98* 695 100 99 97 99 97 99 96 696 100* 100* 100* 99* 99* 99* 100* 697 100 91 0 98 8 19 93 698 99 0 0 99 0 83 56 699 100 99 0 99 0 41 99 700 93* 0* 0* 53* 0* 0* 0* 701 100 100 91 99 7 100 95 702 100 100 99 99 59 86 99 703 100 100 100 99 39 98 97 704 64 80 0 0 0 9 0 705 99 100 99 99 100 100 100 706 57 100 0 99 25 86 100 Cmpd. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J
707 - - 100 100 - 100 99 67 100 100
708 - - 100 0 - 82 99 7 80 89
709 - - 100 100 - 100 99 100 100 100
710 - - 100 100 - 100 98 99 100 98
711 - - 100 100 - 99 99 98 99 99
712 - - 100* 57* - 0* 95 7* 86* 61*
713 - - 100 100 - 100 100 78 100 100
714 - - 100 100 - 100 99 100 100 100
715 - - 100 100 - 78 99 100 99 73
716 - - 100 100 - 95 100 100 99 99
717 - - 100 100 - 0 99 0 96 79
718 - - 100 100 - 97 100 99 100 100
719 - - 99 100 - 98 99 99 100 100
720 0 0 0 0 0 0 0 - 0 94
721 0 0 0 0 0 0 0 - 0 0
722 9 0 0 0 0 0 0 - 0 0
723 - - 100 99 - 0 97 66 68 95
724 - - 100 100 - 97 98 0 100 99
725 - - 100 99 - 73 99 15 91 98
726 - - 99 99 - 0 99 0 80 89
727 - - 98 0 - 0 89 15 74 21
728 - - 100 100 - 100 99 100 100 100
729 - - 100 100 - 99 99 - 100 100
730 - - 100 100 - 99 100 9 99 100
731 - - 99 100 - 99 100 0 99 100
732 - - 100 100 - 100 99 0 99 100
733 - - 100 100 - 100 100 41 100 100
734 - - 100 99 - 99 99 41 100 95
735 - - 100 100 - 99 100 9 100 100
736 - - 99 100 - 97 100 99 100 100
737 - - 100 100 - 100 100 100 100 100
738 - - 100 100 - 100 100 96 100 100
739 - - 100 100 - 100 100 100 100 100
740 37 99 100 100 0 100 100 - 100 100
741 100 99 92 0 99 72

Claims

CLAIMSWhat is claimed is:
1. A compound selected from Formula 1, JV-oxides, and salts thereof,
Figure imgf000260_0001
J iS Q2 Or R1;
X is N, CR2 Or CQ3; Y is N or CR3; Z is N or CR4;
Q1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5a; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R78R7^)W1; W1 is a phenyl ring optionally substituted with up to 5 substituents independently selected from R5a; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from
S(=O)p(=NR6)f, the ring optionally substituted with up to 5 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members;
Q2 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5b; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5^ on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W2; W2 is a phenyl ring optionally substituted with up to 5 substituents independently selected from R5^; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from
S(=O)p(=NR6)f, the ring optionally substituted with up to 5 substituents independently selected from R5^ on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members;
Q3 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5c; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(=0) and C(=S), and the sulfur atom ring members are independently selected from S(=O)p(=NR6)f, each ring or ring system optionally substituted with up to 5 substituents independently selected from R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7 aR715) W3; W3 is a phenyl ring optionally substituted with up to 5 substituents independently selected from R5c; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from
S(=O)p(=NR6)f, the ring optionally substituted with up to 5 substituents independently selected from R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2 C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; R1 is C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C1-C7 haloalkyl, C2-C7 haloalkenyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C1-C7 alkoxy, C { -C7 haloalkoxy, C2-C7 alkoxyalkyl, C { -C7 alkylthio,
C1-C7 haloalkylthio, C2-C7 alkylthioalkyl, C1-C7 alkylsulfmyl, C1-C7 alkylsulfonyl, C1-C7 haloalkylsulfinyl, C1-C7 haloalkylsulfonyl, C1-C7 alkylamino, C2-C7 dialkylamino, C2-C7 alkylcarbonylamino or C1-C7 hydroxyalkyl; each R2, R3 and R4 is independently H, halogen, cyano, amino, nitro, -CHO,
C2-C7 alkenyl, C2-C7 alkynyl, C2-C7 haloalkenyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C1-C7 alkoxy, C1-C7 haloalkoxy, C2-C7 alkoxyalkyl, C1-C7 alkylthio, C1-C7 haloalkylthio, C2-C7 alkylthioalkyl, C1-C7 alkylsulfmyl, C1-C7 alkylsulfonyl, C1-C7 haloalkylsulfinyl, C1-C7 haloalkylsulfonyl, C1-C7 alkylamino, C2-C7 dialkylamino, C1-C7 hydroxyalkyl, -SCN or CH=NOR11; or C1-C7 alkyl or C1-C7 haloalkyl, each optionally substituted with up to 3 substituents independently selected from hydroxy, cyano, C(=O)OR8, C(=O)NR9aR9b, C(=O)R10 and CH=NOR11; each R5a, R5b and R5c is independently halogen, cyano, hydroxy, nitro, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C1-C7 haloalkyl, C2-C7 haloalkenyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, Cg-C14 cycloalkylcycloalkyl, C3-C7 cycloalkoxy, C3-C7 halocycloalkoxy, C1-C7 alkoxy, C1-C7 haloalkoxy, C1-Cg alkylthio, C1-C7 halo alky lthio, C1-C7 alkylsulfmyl, C1-C7 alkylsulfonyl, C1-C7 haloalkylsulfinyl, C1-C7 haloalkylsulfonyl, C1-C7 alkylamino, C2-C7 dialkylamino, C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl, C2-C7 alkylcarbonylamino, C3-C10 trialkylsilyl, SF5, -SCN, C(=S)NH2 or -U-V-T; each U is independently O, S(=O)n, NR12 or a direct bond; each V is independently C1-Cg alkylene, C2-Cg alkenylene, C3-Cg alkynylene, C3-C6 cycloalkylene or C3-C6 cycloalkenylene, wherein up to 3 carbon atoms are independently selected from C(=O), each optionally substituted with up to 5 substituents independently selected from halogen, cyano, nitro, hydroxy, C1-C6 alkyl, C1-C6 haloalky, C1-C6 alkoxy and C1-C6 haloalkoxy; each T is independently NR13aR13b, OR14 or S(=O)nR14; each R7a is independently H, cyano or C1-C4 alkyl; each R7b is independently H or C1-C4 alkyl; or a pair of R7a and R7b attached to the same carbon atom are taken together with the carbon atom to form a 3- to 6-membered saturated carbocyclic ring; each R6 is independently H, cyano, C1-C3 alkyl or C1-C3 haloalkyl; each R8, R9a, R9b? RlO and Rll is independently H, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C1-C7 haloalkyl, C2-C7 haloalkenyl, C3-C7 cycloalkyl or C3-C7 halocycloalkyl; each R12 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-Cg cycloalkylcarbonyl, C4-Cg cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); each R13a and R13b is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); or a pair of R13a and R13^ attached to the same nitrogen atom are taken together with the nitrogen atom to form a 3- to 6-membered heterocyclic ring, the ring optionally substituted with up to 5 substituents independently selected from R15; each R14 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl,
C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); each R15 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy; each n is independently 0, 1 or 2; and each p and f are independently 0, 1 or 2 in each instance of S(=O)p(=NR6)f, provided that the sum of p and f is 0, 1 or 2; provided that:
(a) when J is R1, then X is CQ3; (b) when J is Q2, then X is N or CR2, and if X is N or CH, then Z is other than
CH;
(c) for compounds other than l-(4-chlorophenyl)-5-(4-fluorophenyl)-2- methyl-lH-imidazole or 4-chloro-l-(4-chlorophenyl)-5-(4- fluorophenyl)-2-methyl-lH-imidazole, when Q1 is a phenyl ring which is unsubstituted by R5a at both ortho positions, then when X is N or CR2 and Q2 is a phenyl ring, the Q2 phenyl ring is substituted by at least one R5b at an ortho position; and when X is CQ3 and Q3 is a phenyl ring, the Q3 phenyl ring is substituted by at least one R5c at an ortho position;
(d) at least one and no more than two of X, Y and Z is nitrogen; (e) the compound is not a compound of formula F-I through F-4, as shown below
Figure imgf000265_0001
F-4
(g) the compound is not 4-[2-ethyl-l-(4-methoxyphenyl)-lH-imidazol-5-yl]- pyridine, 4-[l-(4-methoxyphenyl)-2-methyl-lH-imidazol-5-yl]pyridine or 3,5-dichloro-2-(4-iodo-5-phenyl-lH-l,
2,3-triazol-l-yl)pyridine; and
(e) when J is Q2, X is CR2, Y is N and Z is N, then R2 is other than Η.
A compound of Claim 1 wherein:
Q1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5a; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from up to 2 O, up to 2 S and up to 3 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)s(=NR6)f, the ring optionally substituted with up to 3 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W!;
W1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members;
Q2 is is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5b; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from up to 2 O, up to 2 S and up to 3 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)s(=NR6)f, the ring optionally substituted with up to 3 substituents independently selected from R5b on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W2;
W2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R5b on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy,
C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; Q3 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5c; or a 5- to 6-membered fully unsaturated heterocyclic ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from up to 2 O, up to 2 S and up to 3 N atoms, wherein up to 2 carbon atom ring members are independently selected from C(=O) and C(=S), and the sulfur atom ring members are independently selected from S(=O)s(=NR6)f, the ring optionally substituted with up to 3 substituents independently selected from R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W3; W3 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring optionally substituted with up to 3 substituents independently selected from R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; each R7a is independently H, cyano or methyl; each R7b is independently H or methyl; or a pair of R7a and R7b attached to the same carbon atom are taken together with the carbon atom to form a cyclopropyl ring.
3. A compound of Claim 2 wherein:
Q1 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5a on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W!;
W1 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5a; Q2 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5b on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W2;
W2 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5b; Q3 is a phenyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazolyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 3 substituents independently selected from R5c on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C(R7aR7b)W3;
W3 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5c; each R2, R3 and R4 is independently H, halogen, C2-C3 alkenyl, C2-C3 alkynyl, C2-C3 haloalkenyl, C3-Cg cycloalkyl, C1-C3 alkoxy, C1-C3 alkylthio, C1-C3 alkylamino, C2-C4 dialkylamino or C1-C3 hydroxyalkyl; or C1-C3 alkyl or C1-C3 haloalkyl, each optionally substituted with up to 1 substituent independently selected from hydroxy, cyano, C(=O)OR8, C(=O)NR9aR9b, Q=O)R1 ° and
CH=NOR11; each R5a, R5b and R5c is independently halogen, cyano, C1-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, C1-C3 haloalkyl, C3 cycloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylamino, C2-C4 dialkylamino C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonylamino or -U-V-T;
U is O or NH;
V is C2-C4 alkylene;
T is NR13aR13b or OR14; each R7a and R7b is independently H or methyl; each R8, R9a, R9b, R10 and R11 is independently H or methyl; each R13a and R13b is independently H, C1-C6 alkyl or C1-C6 haloalkyl; and each R14 is independently H, C1-C6 alkyl or C1-C6 haloalkyl.
4. A compound of Claim 3 wherein: Q1 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5a; Q2 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5b; and Q3 is a phenyl or pyridinyl ring optionally substituted with up to 3 substituents independently selected from R5c.
5. A compound of Claim 4 wherein: each R2, R3 and R4 is independently H, halogen, cyano or C1-C3 alkyl; and each R5a, R5b and R5c is independently halogen, cyano, C1-C3 alkyl, C2-C3 alkenyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 alkylthio or C1-C3 alkylamino.
6. A compound of Claim 5 wherein:
J is Q2; X is CR2;
Y is N;
Z is CR4; each R2 and R4 is independently Cl, Br, I or C1-C2 alkyl; each R5a and R5b is independently F, Cl, Br, cyano, C1-C2 alkyl, C1-C2 haloalkyl or C1-C2 alkoxy; and one of the Q1 and Q2 rings is substituted with 2 to 3 substituents and the other of the Q1 and Q2 rings is substituted with 1 to 2 substituents.
7. A compound of Claim 1 which is selected from the group consisting of:
4-chloro- 1 -(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)- lH-imidazole;
4-chloro- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl- lH-imidazole;
2,4-dichloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2,4-dimethyl-lH-imidazole;
4-chloro- 1 -(4-chlorophenyl)-2-methyl-5-(2,4,6-trifluorophenyl)- lH-imidazole; l-(4-chlorophenyl)-2,4-dimethyl-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-2,4-dichloro-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl-lH- imidazole; l-(4-chlorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazole;
4-chloro- l-(4-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH- imidazole;
4-chloro- 1 -(4-chloro-3-fluorophenyl)-2-methyl-5-(2,4,6-trifluorophenyl)- IH- imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dimethyl-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chloro-3-fluorophenyl)-5-(2,6-difluorophenyl)-2,4-dimethyl-lH-imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,6-difluorophenyl)-lH-imidazole;
4-chloro- l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2- methyl- lH-imidazole; l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl-lH- imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH- imidazole;
4-chloro- 1 -(3-fluorophenyl)-2-methyl-5-(2,4,6-trifluorophenyl)- lH-imidazole;
2,4-dichloro- 1 -(3-fluorophenyl)-5-(2,4,6-trifluorophenyl)- lH-imidazole;
4-chloro- 1 -(3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl- IH- imidazole; l-(3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl-lH- imidazole; l-(3-fluorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazole;
4-chloro-l-(4-chlorophenyl)-2-methyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-2,4-dimethyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-2,4-dichloro-5-(2,3,6-trifluorophenyl)-lH-imidazole;
4-chloro-l-(3-fluorophenyl)-2-methyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(3-fluorophenyl)-2,4-dimethyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(3-fluorophenyl)-2,4-dichloro-5-(2,3,6-trifluorophenyl)-lH-imidazole;
4-chloro-5-(2-chloro-4-fluorophenyl)- 1 -(4-chlorophenyl)-2-methyl- lH-imidazole;
5-(2-chloro-4-fluorophenyl)-l-(4-chlorophenyl)-2,4-dimethyl-lH-imidazole;
5-(2-chloro-4-fluorophenyl)-l-(4-chlorophenyl)-2,4-dichloro-lH-imidazole;
4-chloro-l-(4-chlorophenyl)-5-(2,6-difluoro-3-methoxyphenyl)-2-methyl-lH- imidazole;
4-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(4-fluorophenyl)-2-methyl- IH- imidazole;
4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-l-(4-methylphenyl)-lH- imidazole;
4-[4-chloro-l-(4-chlorophenyl)-2-methyl-lH-imidazol-5-yl]-3,5- difluorobenzonitrile;
2-bromo-4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3-fluorophenyl)-lH- imidazole;
2-chloro-l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-4- methyl- lH-imidazole;
2-chloro-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol-l- yl]pyridine;
2-bromo-4-chloro-5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluorophenyl)-lH- imidazole;
4-chloro-5-(2,6-difluoro-3-methoxyphenyl)-2-methyl-l-(4-methylphenyl)-lH- imidazole;
4-chloro-5-(2,6-difluro-3-methoxyphenyl)- 1 -(4-fluorophenyl)-2 -methyl- IH- imidazole;
2,4-dichloro-5-(2,6-difluoro-3-methoxyphenyl)-l-(4-fluorophenyl)-lH-imidazole;
2,4-dichloro-l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-3-methoxyphenyl)-lH- imidazole;
4-chloro-l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-3-methoxyphenyl)-2- methyl- lH-imidazole;
2-chloro-5-[2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 - yl]pyridine; 4-chloro-l-[3-(difluoromethoxy)phenyl]-5-(2,6-difluoro-3-methoxyphenyl)-2- methyl- lH-imidazole;
3-[4-chloro-l-(4-chlorophenyl)-2-methyl-lH-imidazol-5-yl]-2,4- difluorobenzonitrile;
4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3,4-difluorophenyl)-2-methyl-lH- imidazole;
4-chloro-l-(3-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH- imidazole;
4-bromo-2-chloro-l-(4-chlorophenyl)-5-(2,6-difluoro-3-methoxyphenyl)-lH- imidazole;
5-[2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazol-yl]-2- methylpyridine;
5-[2,4-dibromo-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 -yl]-2- methylpyridine;
2-chloro-5-(4-chlorophenyl)-l-(2,6-difluoro-4-methoxyphenyl)-4-methyl- imidazole;
4-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(4-fluorophenyl)-lH-imidazole-2- carboxaldehyde oxime;
4-chloro-l-(2,6-dichlorophenyl)-2-methyl-5-[(2,4,6-trifluorophenyl)methyl]-lH- imidazole;
2-chloro-5-[2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)- lH-imidazol- 1 -yl-4- methyljpyridine;
4-(2-chloro-4-fluorophenyl)-5-[(2,4-difluorophenyl)methyl]-l,3-dimethyl-lH- pyrazole; and
2-chloro- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)-4-methyl- lH-imidazole;
2-chloro- 1 -(4-chlorophenyl)-4-methyl-5-(2,4,6-trifluorophenyl)- lH-imidazole;
2-chloro- l-(4-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH- imidazole;
2-chloro- 1 -(4-chloro-3-fluorophenyl)-4-methyl-5-(2,4,6-trifluorophenyl)- IH- imidazole;
2-chloro- l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-4- methyl- lH-imidazole;
2-chloro- 1 -(3-fluorophenyl)-4-methyl-5-(2,4,6-trifluorophenyl)- lH-imidazole;
2-chloro- 1 -(3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl- IH- imidazole;
2-chloro- l-(4-chlorophenyl)-4-methyl-5-(2,3,6-trifluorophenyl)-lH-imidazole;
2-chloro- l-(3-fluorophenyl)-4-methyl-5-(2,3,6-trifluorophenyl)-lH-imidazole;
2-chloro- l-(4-chlorophenyl)-5-(2,6-difluoro-3-methyoxyphenyl)-4-methyl-lH- imidazole;
2-chloro-5-(2,6-difluoro-4-methoxyphenyl)- 1 -(4-fluorolphenyl)-4-methyl- IH- imidazole;
2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-l-(4-methylphenyl)-lH- imidazole;
4-[2-chloro-l-(4-chlorophenyl)-4-methyl-lH-imidazol-5-yl]-3,5- difluorobenzonitrile;
2-chloro-5-(2,6-difluoro-3-methoxyphenyl)-4-methyl-l-(4-methylphenyl)-lH- imidazole;
2-chloro-5-(2,6-difluoro-3-methoxyphenyl)- 1 -(4-fluorophenyl)-4-methyl- IH- imidazole;
2-chloro-l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-3-methoxyphenyl)-lH- imidazole;
2-chloro-l-[3-(difluoromethoxy)phenyl]-5-(2,6-difluoro-3-methoxyphenyl)-4- methyl- lH-imidazole;
3-[2-chloro-l-(4-chlorophenyl)-4-methyl-lH-imidazol-5-yl]-2,4- difluorobenzonitrile;
2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-l-(3,4-difluorophenyl)-4-methyl-lH- imidazole;
2-chloro-l-(3-chlorophenyl)-5-(2,6-difluoro-4-methoxphenyl)-4-methyl-lH- imidazole;
2-fluoro-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol-l- yl]pyridine;
2-bromo-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl- lH-imidazol- 1 - yl]pyridine;
2-methoxy-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol- l-yl]pyridine;
2-trifluoromethoxy-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH- imidazol- 1 -yl]pyridine;
2-trifluoromethyl-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH- imidazol- 1 -yl]pyridine;
2-cyano-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol-l- yl]pyridine;
3-fluoro-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol-l- yl]pyridine;
3-bromo-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl- lH-imidazol- 1 - yl]pyridine;
3-chloro-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol-l- yl]pyridine;
3-methoxy-5-[2-chloro-5-(2,6-difluoro-4-methoxyphenyl)-4-methyl-lH-imidazol- l-yl]pyridine; l-(4-chlorophenyl)-5-(2,6-difluoro-4-ethoxyphenyl)-2,4-dimethyl-lH-imidazole; l-(4-fluorophenyl)-5-(2,6-difluoro-4-ethoxyphenyl)-2,4-dimethyl-lH-imidazole; l-(3-chlorophenyl)-5-(2,6-difluoro-4-ethoxyphenyl)-2,4-dimethyl-lH-imidazole; l-(3-fluorophenyl)-5-(2,6-difluoro-4-ethoxyphenyl)-2,4-dimethyl-lH-imidazole; 1 -(4-methylphenyl)-5-(2,6-difluoro-4-ethoxyphenyl)-2,4-dimethyl- lH-imidazole; and l-(3-methylphenyl)-5-(2,6-difluoro-4-ethoxyphenyl)-2,4-dimethyl-lH-imidazole.
8. A compound of Claim 1 which is selected from the group consisting of: 4-chloro-l-(4-chlorophenyl)-5-(2,4,6-trifluorophenyl)-lH-imidazole; 4-chloro-l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2-methyl-lH-imidazole; 2,4-dichloro- 1 -(4-chlorophenyl)-5-(2,6-difluorophenyl)- lH-imidazole; l-(4-chlorophenyl)-2,4-dichloro-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-5-(2,6-difluorophenyl)-2,4-dimethyl-lH-imidazole; 4-chloro-l-(4-chlorophenyl)-2-methyl-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-2,4-dimethyl-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-2,4-dichloro-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl-lH- imidazole; l-(4-chlorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH- imidazole;
4-chloro-l-(4-chlorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH- imidazole;
4-chloro-l-(4-chloro-3-fluorophenyl)-2-methyl-5-(2,4,6-trifluorophenyl)-lH- imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,4,6-trifluorophenyl)-lH-imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dimethyl-5-(2,4,6-trifluorophenyl)-lH- imidazole; l-(4-chloro-3-fluorophenyl)-5-(2,6-difluorophenyl)-2,4-dimethyl-lH-imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,6-difluorophenyl)-lH-imidazole; l-(4-chloro-3-fluorophenyl)-5-(2,6-difluorophenyl)-2,4-dimethyl-lH-imidazole; 4-chloro-l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2- methyl- lH-imidazole; l-(4-chloro-3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl-lH- imidazole; l-(4-chloro-3-fluorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH- imidazole;
4-chloro-l-(3-fluorophenyl)-2-methyl-5-(2,4,6-trifluorophenyl)-lH-imidazole;
2,4-dichloro- 1 -(3-fluorophenyl)-5-(2,4,6-trifluorophenyl)- lH-imidazole; l-(3-fluorophenyl)-5-(2,4,6-trifluorophenyl)-2,4-dimethyl-lH-imidazole;
4-chloro-l-(3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH- imidazole; l-(4-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2,4-dimethyl-lH- imidazole; l-(3-fluorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazole; l-(3-fluorophenyl)-2,4-dichloro-5-(2,6-difluoro-4-methoxyphenyl)-lH-imidazole; l-(3-fluorophenyl)-2,4-dimethyl-5-(2,6-difluoro-4-methoxyphenyl)-lH- imidazole;
4-chloro-l-(3-fluorophenyl)-5-(2,6-difluoro-4-methoxyphenyl)-2-methyl-lH- imidazole;
4-chloro-l-(4-chlorophenyl)-2-methyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(4-chlorophenyl)-2,4-dimethyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; and l-(4-chlorophenyl)-2,4-dichloro-5-(2,3,6-trifluorophenyl)-lH-imidazole;
4-chloro-l-(3-fluorophenyl)-2-methyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(3-fluorophenyl)-2,4-dimethyl-5-(2,3,6-trifluorophenyl)-lH-imidazole; l-(3-fluorophenyl)-2,4-dichloro-5-(2,3,6-trifluorophenyl)-lH-imidazole;
4-chloro-5-(2-chloro-4-fluorophenyl)- 1 -(4-chlorophenyl)-2-methyl- lH-imidazole;
5-(2-chloro-4-fluorophenyl)- 1 -(4-chlorophenyl)-2,4-dimethyl- lH-imidazole; and
5-(2-chloro-4-fluorophenyl)-l-(4-chlorophenyl)-2,4-dichloro-lH-imidazole.
9. A fungicidal composition comprising (a) a compound of Claim 1; and (b) at least one other fungicide.
10. A fungicidal composition comprising (a) a fungicidally effective amount of a compound of Claim 1; and (b) at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
11. A method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Claim 1.
PCT/US2009/043096 2008-05-08 2009-05-07 Fungicidal substituted azoles WO2009137651A2 (en)

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