IP Library › Granted Patent US 7,968,584

Granted Patent B2

US 7,968,584 · App. 12/407,365 · Granted Jun 28, 2011

Substituted arylpyrazoles

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Quick Facts

Patent No.: US 7,968,584
App. No.: 12/407,365
Granted: Jun 28, 2011
Kind: B2

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Abstract

This invention relates to a range of 1-aryl-4-cyclopropylpyrazoles in which the cyclopropyl ring is substituted at the angular position, and pharmaceutically acceptable salts and solvates thereof, to compositions comprising such compounds, processes to their synthesis and their use as parasiticides.

Claims (165)

1. A pharmaceutical composition comprising a compound of Formula (I)

wherein:

X is CR 10 ;

R 1 is C 1-6 haloalkyl, C 1-6 haloalkoxy, or SF 5 ;

R 2 is cyano, C(O)OH, het, S(O) n R 11 , C(O)NR a R b , C(S)NR a R b , or C(O)OC 1-6 alkyl;

R a and R b are each independently hydrogen or S(O) n R 11 ;

or either one or both of R a and R b are independently C 1-6 alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, alkanoyl, or C(O)OC 1-6 alkyl, each of which R a or R b may be optionally and independently further substituted by one or more substituents selected from the group consisting of, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR c R d , NR c C(O)R d , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, C 3-8 cycloalkylC 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkanoyl, —C(O)OC 1-6 alkyl, C 1-6 haloalkyl, C 3-8 halocycloalkyl, C 1-6 haloalkoxy, C 1-6 haloalkanoyl, —C(O)OC 1-6 haloalkyl, amino, NR c R d , het, phenyl and S(O) n R 11 ;

R 3 , R 4 , R 5 and R 6 are each independently selected from hydrogen, halo, cyano, hydroxy, C(O)OH, nitro, phenyl, or S(O) n R 11 ;

R 7 is fluoro or chloro;

R 6 is cyano;

R 9 is hydrogen, halo, —S(O) n R 11 , NR e R f , C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, or —C 3-8 cycloalkylC 1-6 alkoxy;

R e and R f are each independently hydrogen, het, phenyl or S(O) n R 11 ;

or either one or both of R e and R f are independently C 1-6 alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, C 1-6 alkanoyl, C(O)OC 1-6 alkyl, —C(O)OC 1-6 alkylC 3-8 cycloalkyl, or —C(O)OC 3-8 cycloalkyl, each of which R e or R f may be optionally and independently further substituted by one or more substituents selected from the group consisting of, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, —C(O)NR c R d , NR c C(O)R d , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, C 3-8 cycloalkylC 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkanoyl, —C(O)OC 1-6 alkyl, C 1-6 haloalkyl, C 3-8 halocycloalkyl, C 1-6 haloalkoxy, C 1-6 haloalkanoyl, —C(O)OC 1-6 haloalkyl, amino, NR c R d , het, phenyl, and S(O) n R 11 ;

R 10 is halo, C 1-6 alkyl, or C 1-6 alkoxy and when R 10 is C 1-6 alkyl or C 1-6 alkoxy it may optionally be substituted with one or more halo substituents;

each of R c and R d are independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkylC 1-6 haloalkyl, C 1-6 alkanoyl, C 1-6 haloalkanoyl, C(O)OC 1-6 alkyl, het, phenyl or S(O) n R 11 ;

n is independently 0, 1 or 2;

R 11 is independently hydrogen, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, amino, C 1-6 alkyl amino, or di C 1-6 alkyl amino;

each phenyl may be optionally substituted by one or more further substitutents selected from the group consisting of halo, cyano, nitro, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, amino, C 1-6 alkyl amino, di C 1-6 alkyl amino, —NHS(O) n R 11 , and S(O) n R 11 ;

and each het independently represents a four to seven membered heterocyclic ring, which is aromatic or non-aromatic, unsaturated, partially saturated or saturated and which contains one or more heteroatoms selected from nitrogen, N-oxide, oxygen, and sulphur and wherein said heterocyclic ring is optionally substituted, where the valence allows, with one or more substituents selected from the group consisting of halo, cyano, nitro, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, OC(O)C 1-6 alkyl, C 1-6 alkanoyl, C(O)OC 1-6 alkyl and NR g R h , where R g and R h are each independently selected from hydrogen, C 1-6 alkyl or C 2-6 alkenyl, and where each of the above groups may include one or more optional substituents where chemically possible independently selected from the group consisting of cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR c R d , NR c C(O)R d , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, C 3-8 cycloalkylC 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkanoyl, —C(O)OC 1-6 alkyl, C 1-6 haloalkyl, C 3-8 halocycloalkyl, C 1-6 haloalkoxy, C 1-6 haloalkanoyl, —C(O)OC 1-6 haloalkyl, amino, C 1-6 alkyl amino, di C 1-6 alkyl amino, phenyl and S(O) n R 11 ; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

2. The composition of claim 1 wherein the compound of Formula (I) is selected from:

5-amino-1-[2,6-dichloro-4-pentafluorothiophenyl]-4-[1-(methylsulfonyl)cyclopropyl]-1H-pyrazole-3-carbonitrile;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

methyl 1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}cyclopropane-carboxylate;

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[2,2-difluoro-1-(methylsulfonyl)cyclopropyl]-1H-pyrazole-3-carbonitrile;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-N,N-dimethylcyclopropanecarboxamide;

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[1-(methylsulfonyl)cyclopropyl]-1H-pyrazole-3-carbonitrile;

methyl 1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}cyclopropane-carboxylate;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-2,2-difluoro-N,N-dimethyl-cyclopropanesulfonamide;

5-amino-4-(1-cyanocyclopropyl)-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile;

5-amino-4-(1-cyanocyclopropyl)-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazole-3-carbonitrile;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-2,2-difluorocyclopropanesulfonamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(isobutylamino)-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-isopropylcyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(2-fluoroethyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{5-[(2-amino-2-oxoethyl)amino]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-cyclopropanecarboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-2,2-dichlorocyclopropane-carboxamide;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-(pyridin-4-ylmethyl)cyclopropanecarboxamide;

isopropyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}carbamate;

1-(3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-{[2-(1H-1,2,4-triazol-1-yl)ethyl]amino}-1H-pyrazol-4-yl)cyclopropanecarboxamide;

1-{3-cyano-5-[(2-cyanoethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-(5-amino-3-cyano-1-{2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl}-1H-pyrazol-4-yl)cyclopropanecarboxamide;

1-(3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-{[3-(methylthio)propyl]amino}-1H-pyrazol-4-yl)-cyclopropanecarboxamide;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-[(5-methyl-4H-1,2,4-triazol-3-yl)methyl]cyclopropanecarboxamide;

1-{3-cyano-5-[(cyclopropylmethyl)(methyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

[1-(fluoromethyl)cyclopropyl]methyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}carbamate;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(methylamino)-1H-pyrazol-4-yl}-2,2-difluorocyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(3,3,3-trifluoropropyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-(5-{[(2-chloro-1,3-thiazol-5-yl)methyl]amino}-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl)cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(isoxazol-5-ylmethyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

N-3-{4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}-beta-alaninamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(5,5,5-trifluoropentyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(propylamino)-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-5-[(cyclobutylmethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(dimethylamino)-1H-pyrazol-4-yl}cyclopropanecarboxamide;

ethyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-1H-pyrazol-5-yl}carbamate;

2,2-dichloro-1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(methylamino)-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-1H-pyrazol-4-yl}-2,2-dichlorocyclopropanecarboxamide;

1-{3-cyano-5-({2-[(cyclopropylmethyl)amino]-2-oxoethyl}amino)-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{5-[(4-amino-4-oxobutyl)amino]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(1,3-thiazol-2-ylmethyl)amino]-1H-pyrazol-4-yl}-cyclopropanecarboxamide;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-(2-methoxyethyl)cyclopropanecarboxamide;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-(2-hydroxyethyl)cyclopropanecarboxamide;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-(pyridin-2-ylmethyl)cyclopropanecarboxamide;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-(pyridin-3-ylmethyl)cyclopropanecarboxamide;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-(2-hydroxy-2-methylpropyl)cyclopropanecarboxamide;

1-(3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-{[2-(1-methyl-1H-pyrazol-4-yl)ethyl]amino}-1H-pyrazol-4-yl)cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(dimethylamino)-1H-pyrazol-4-yl}-2,2-difluorocyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(methylthio)-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(2-methoxyethyl)(methyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-(5-{[(5-chloro-1,3-dimethyl-1H-pyrazol-4-yl)methyl]amino}-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl)cyclopropanecarboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-2,2-difluorocyclopropanecarboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-2,2-difluorocyclopropanecarboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-methylcyclopropane-carboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-N-cyclopropylcyclopropane-carboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-N-(cyclopropylmethyl)-cyclopropanecarboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-N-pyridin-2-ylcyclopropane-carboxamide;

1-(3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-{[(1E)-(dimethylamino)methylene]amino}-1H-pyrazol-4-yl)cyclopropanecarboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-(2,2,2-trifluoroethyl)-cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-5-(methylamino)-1H-pyrazol-4-yl}-2,2-difluoro-cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-5-(methylamino)-1H-pyrazol-4-yl}cyclopropane-carboxamide;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-N-methylcyclopropanecarboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-2,2-dimethylcyclopropane-carboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(4H-1,2,4-triazol-3-ylmethyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-(3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-{[(1-methylcyclopropyl)methyl]amino}-1H-pyrazol-4-yl)cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-({4-[(methylamino)sulfonyl]benzyl}amino)-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-({4-[(methylsulfonyl)amino]benzyl}amino-1H-pyrazol-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(tetrahydro-2H-pyran-4-ylmethyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-(3-isopropoxypropyl)cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-({2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl}amino)-1H-pyrazol-4-yl}cyclopropanecarboxamide;

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[2,2-difluoro-1-(methylthio)cyclopropyl]-1H-pyrazole-3-carbonitrile;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{5-(benzylamino)-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(pyridin-2-ylmethyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(2,2-dimethylpropyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-(3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-{[4-(methylsulfonyl)benzyl]amino}-1H-pyrazol-4-yl)cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(pyridin-4-ylmethyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(2,2,2-trifluoroethyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(1H-imidazol-2-ylmethyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-2,2-difluorocyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{5-chloro-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{5-chloro-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-2,2-difluorocyclopropane-carboxamide;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-2,2-dimethylcyclopropane-carboxylic acid;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(methylamino)-1H-pyrazol-4-yl}cyclopropane-carboxamide;

cyclopropylmethyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}carbamate;

ethyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}methylcarbamate;

1-[({4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}amino)methyl]cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-methyl-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1--[2,6-dichloro-4-(trifluoromethoxy)phenyl]-1H-pyrazol-4-yl}-cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(2-fluoro-2-methylpropyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

methyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}carbamate;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-1H-pyrazol-4-yl}-2,2-difluorocyclopropane-carboxamide;

ethyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}carbamate;

cyclopropylmethyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}methylcarbamate;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(4,4,4-trifluorobutyl)amino]-1H-pyrazol-4-yl}-cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(ethylamino)-1H-pyrazol-4-yl}cyclopropanecarboxamide;

tert-butyl {1-[({4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}amino)methyl]cyclopropyl}carbamate;

1-(3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-{[4-(trifluoromethyl)benzyl]amino}-1H-pyrazol-4-yl)cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(2-isopropoxyethyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-vinyl-1H-pyrazol-4-yl}cyclopropanecarboxamide;

cyclobutyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}carbamate;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(4-fluorobenzyl)amino]-1H-pyrazol-4-yl}cyclopropane-carboxamide;

ethyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-5-yl}carbamate;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

methyl 1-{5-(benzylamino)-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}cyclopropanecarboxylate;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-2,2-difluorocyclopropanecarboxamide;

1-{3-cyano-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-2,2-difluorocyclopropanecarboxamide;

4-(1-cyanocyclopropyl)-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(methylamino)-1H-pyrazole-3-carbonitrile;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}cyclopropanecarbothioamide;

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[1-(1,3-thiazol-2-yl)cyclopropyl]-1H-pyrazole-3-carbonitrile;

1-{5-amino-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-(methylsulfonyl)-cyclopropanecarboxamide;

1-{3-cyano-5-[(2-cyclopropylethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

5 amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[2,2-difluoro-1-(methylsulfinyl)cyclopropyl]-1H-pyrazole-3-carbonitrile;

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[2,2-difluoro-1-(methylsulfinyl)cyclopropyl]-1H-pyrazole-3-carbonitrile;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(isopropylamino)-1H-pyrazol-4-yl}cyclopropane-carboxamide;

1-{3-cyano-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-5-(isopropylamino)-1H-pyrazol-4-yl}-2,2-difluorocyclopropanecarboxamide;

4-(1-cyanocyclopropyl)-5-[(cyclopropylmethyl)amino]-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazole-3-carbonitrile;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[({1-[(methylsulfonyl)amino]cyclopropyl}methyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-(5-{[(1-aminocyclopropyl)methyl]amino}-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl)cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(methylsulfinyl)-1H-pyrazol-4-yl}cyclopropanecarboxamide;

1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(methylsulfonyl)-1H-pyrazol-4-yl}cyclopropanecarboxamide; and

4-({4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}amino)butanoic acid;

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

3. A method of treating a parasitic infection comprising treating an animal with an effective amount of a compound of Formula (I)

wherein

X is CR 10 ;

R 1 is C 1-6 haloalkyl, C 1-6 haloalkoxy, or SF 5 ;

R 2 is cyano, C(O)OH, het, S(O) n R 11 , C(O)NR a R b , C(S)NR a R b , or C(O)OC 1-6 alkyl;

R a and R b are each independently hydrogen or S(O) n R 11 ;

or either one or both of R a and R b are independently C 1-6 alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, C 1-6 alkanoyl, or C(O)OC 1-6 alkyl, each of which R a or R b may be optionally and independently further substituted by one or more substituents selected from the group consisting of, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR c R d , NR c C(O)R d , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, C 3-8 cycloalkylC 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkanoyl, —C(O)OC 1-6 alkyl, C 1-6 haloalkyl, C 3-8 halocycloalkyl, C 1-6 haloalkoxy, C 1-6 haloalkanoyl, —C(O)OC 1-6 haloalkyl, amino, NR c R d , het, phenyl, and S(O) n R 11 ;

R 3 , R 4 , R 5 and R 6 are each independently selected from hydrogen, halo, cyano, hydroxy, C(O)OH, nitro, phenyl, or S(O) n R 11 ;

R 7 is fluoro or chloro;

R 8 is cyano;

R 9 is hydrogen, halo, —S(O) n R 11 , NR e R f , C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, or —C 3-8 cycloalkylC 1-6 alkoxy;

R e and R f are each independently hydrogen, het, phenyl or S(O) n R 11 ;

or either one or both of R e and R f are independently C 1-6 alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, C 1-6 alkanoyl, C(O)OC 1-6 alkyl, —C(O)OC 1-6 alkylC 3-8 cycloalkyl, or —C(O)OC 3-8 cycloalkyl, each of which R e or R f may be optionally and independently further substituted by one or more substituents selected from the group consisting of, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, —C(O)NR c R d , NR c (O)R d , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, C 3-8 cycloalkylC 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkanoyl, —C(O)OC 1-6 alkyl, C 1-6 haloalkyl, C 3-8 halocycloalkyl, C 1-6 haloalkoxy, C 1-6 haloalkanoyl, —C(O)OC 1-6 haloalkyl, amino, NR c R d , het, phenyl, and S(O) n R 11 ;

R 10 is halo, C 1-6 alkyl, or C 1-6 alkoxy and when R 10 is C 1-6 alkyl or C 1-6 alkoxy it may optionally be substituted with one or more halo substituents;

each of R c and R d are independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, haloalkyl, C 3-8 cycloalkylC 1-6 haloalkyl, C 1-6 alkanoyl, C 1-6 haloalkanoyl, C(O)OC 1-6 alkyl, het, phenyl or S(O) n R 11 ;

n is independently 0, 1 or 2;

R 11 is independently hydrogen, hydroxy, C 1-6 alkyl, C 1-6 haloalkyl, amino, C 1-6 alkyl amino, or di C 1-6 alkyl amino;

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 11, 2013

From: PFIZER INC.

To: AH USA 42 LLC

Reel/Frame 029609/0336 →

CONSENT OF PFIZER LTD Recorded Sep 26, 2012

From: PFIZER LTD

To: PFIZER INC.

Reel/Frame 029042/0660 →