US 2007/0167507 A1Published application

4-Carbox pyrazole derivatives useful as anti-viral agents

AssigneesGlaxo Group Limited, SmithKline Beecham Corporation

InventorsGianpaolo Bravi, John Corfield, Richard Grimes, Rossella Guidetti, Victoria Lucy Lovegrove, Jacqueline Mordaunt, Pritom Shah, Martin Slater

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Abstract

Novel antiviral compounds of Formula (I): wherein: A represents hydroxy; R1 represents aryl, heteroaryl bonded through a ring carbon atom, or heterocyclyl bonded through a ring carbon atom, C1-6alkyl or —C5-9cycloalkyl, each of which may be optionally substituted; R2 represents substituted phenyl, or —(CH2)nC5-7cycloalkyl optionally substituted on the cycloalkyl; R3 represents heterocyclyl or heteroaryl; optionally substituted phenyl or optionally substituted —C1-6alkyl; R4 represents hydrogen; and salts, solvates and esters thereof processes for their preparation, pharmaceutical compositions comprising them, and methods of using them in HCV treatment are provided.

Claims15

Dependent claims

A compound of Formula (I):

wherein:
A represents hydroxy;
R1 represents aryl, heteroaryl bonded through a ring carbon atom, or heterocyclyl bonded through a ring carbon atom, each of which may be optionally substituted by one or more substituents selected from —C1-6alkyl, halo, —ORA, SRA, —C(O)NRBRC, —C(O)RD, —CO2H, —CO2RD, —NRBRC, —NREC(O)RD, —NRECO2RD, —NREC(O)NRFRG, —SO2NRFRG, —SO2RD, nitro, cyano, —CF3, —OCF3, NRESO2RD, phenyl and heterocyclyl, wherein the —C1-6alkyl substituent itself may be optionally substituted by one or more substituents selected from —C5-9cycloalkyl, halo, —NRBRC, —C(O)NRBRC, —NREC(O)RD, —SRA, —SO2RD, ORA, oxo, phenyl, heteroaryl or heterocyclyl;
or R1 represents —C1-6alkyl or —C5-9cycloalkyl;
R2 represents phenyl substituted by one or more substituents selected from —C1-6alkyl, halo, —ORA, —SRA, —C(O)NRBRC, —C(O)RD, —CO2H, —CO2RD, —NRBRC, —NREC(O)RD, —NRECO2RD, —NREC(O)NRFRG, —SO2RD, nitro, cyano, and heterocyclyl;
or R2 represents —(CH2)nC5-7cycloalkyl optionally substituted on the cycloalkyl by one or more substitutents selected from —C1-6alkyl, ═CH(CH2)tH, —ORA, —SRA, —C(O)NRBRC, —C(O)RD, —CO2H, —CO2RD, —NRBRC, —NRCC(O)RD, —NRECO2RC, —NREC(O)NRFRG, —SO2NRFRG, —SO2RD, fluoro, nitro, cyano, oxo, and heterocyclyl, or wherein two substituents may together form a C1-2alkylene bridge substituent;
t represents 0, 11 2, 3 or 4;
n represents 0 or 1;
R3 represents heterocyclyl or heteroaryl;
or phenyl optionally substituted by one or more substituents selected from —C1-6alkyl, halo, —ORA, —SRA, —C(O)NRBRC, —C(O)RD, —CO2H, —CO2RD, —NRBRC, —NREC(O)RD, —NRECO2R, —NREC(O)NRFRG, —SO2NRFRG, —SO2RD, nitro, cyano, and heterocyclyl;
or R3 represents —C1-6alkyl optionally substituted by one or more substituents selected from —C1-6alkyl, —ORA, SRA, —C(O)NRBRC, —C(O)RB, —CO2H, —CO2RD, —NRBRC, —NREC(O)RD, —NRECO2RD, —NREC(O)NRFRG, —SO2NRFRG, —SO2RD, fluoro, nitro, cyano, oxo, phenyl, heteroaryl and heterocyclyl,
R4 represents hydrogen;
RA represents hydrogen, —C1-6alkyl, arylalkyl, heteroarylalkyl, aryl, heterocyclyl or heteroaryl;
RB and RC independently represent hydrogen, —C1-6alkyl, aryl, heterocyclyl or heteroaryl;
or RB and RC together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group;
RD is selected from the group consisting of —C1-6alkyl, aryl, heterocyclyl, heteroaryl, arylalkyl, and heteroarylalkyl;
RE represents hydrogen or —C1-6alkyl;
RF and RG are independently selected from the group consisting of hydrogen, —C1-6alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl;
or RF and RG together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group;
or a pharmaceutically acceptable salt, solvate or ester thereof.

17 more elements

A compound selected from the group consisting of:

3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-(4-methylphenyl)-1H-pyrazole-4-carboxylic acid;
1-(1-Cyclohexen-1-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(4-Chloro-3-methylphenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(4-Fluorophenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(6-Indolyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(4-Hydroxyphenyl)-3-[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-carboxylic acid;
1-[4-(Acetylamino)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(4-Biphenylyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[4-(Dimethylamino)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-[4-(methyloxy)phenyl]-1H-pyrazole-4-carboxylic acid;
1-(4-Acetylphenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(trifluoromethyl)oxy]phenyl]-1H-pyrazole-4-carboxylic acid;
1-(4-Cyanophenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-{4-[(Dimethylamino)carbonyl]phenyl}-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-11H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-(3-thienyl)-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole-4-carboxylic acid;
1-(3,5-Dimethylphenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(3-Chloro-5fluorophenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[3,5-Bis(trifluoromethyl)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino)-1H-pyrazole-4-carboxylic acid;
1-(1,3-Benzodioxol-5-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(2,3-Dihydro-1-benzofuran-5-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(2,3-Dihydro-1,4-benzodioxin-6-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-(3,4,5-trifluorophenyl)-1H-pyrazole-4-carboxylic acid;
1-(4-Chlorophenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-[3-(methyloxy)phenyl]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-[4-(methylsulfonyl)phenyl]-1H-pyrazole-4-carboxylic acid;
1-(2-Fluorophenyl)-3-[[((trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(3-Hydroxyphenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-(3-methylphenyl)-1H-pyrazole-4-carboxylic acid;
1-(3-Fluorophenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(4-Aminophenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(3-Chlorophenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{3-[(trifluoromethyl)oxy]phenyl}-1H-pyrazole-4-carboxylic acid;
1-(4-Chloro-3-fluorophenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(3-Amino-4-methylphenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(3-Fluoro-4-methylphenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(3,4-Difluorophenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[(E)-1-Hexen-1-yl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[(E)-2-Cyclohexylethenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-[(E)-4-methyl-1-penten-1-yl]-1H-pyrazole-4-carboxylic acid;
1-[(E)-2-(4-Fluorophenyl)ethenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(4-Ethenylphenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[4-(Hydroxymethyl)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(4-Ethylphenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-[4-(1-methylethyl)phenyl]-1H-pyrazole-4-carboxylic acid;
1-(5-Acetyl-2-thienyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(5-Chloro-2-thienyl)-3-{[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-(5-methyl-2-thienyl)-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-(5-phenyl-2-thienyl)-1H-pyrazole-4-carboxylic acid;
1-((4-Methyl)cyclohexen-1-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](tetrahydro-2H-pyran-4-yl)amino]-1H-pyrazole-4-carboxylic acid;
1-(6-Benzofuranyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(Cyclohepten-1-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](tetrahydro-2H-pyran-4-yl)amino]-1H-pyrazole-4-carboxylic acid;
1-((4-Methyl)cyclohexen-1-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-(methylsulfonyl)-4-piperidinyl]amino]-1H-pyrazole-4-carboxylic acid;
1-((4,4-Dimethyl)cyclohexen-1-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](tetrahydro-2H-pyran-4-yl)amino]-1H-pyrazole-4-carboxylic acid;
1-(3-Chloro-4-benzyloxyphenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(4-Benzyloxy-cyclohexen-1-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1)-1H-pyrazole-4-carboxylic acid;
1-(4,4-Dimethyl)cyclohexen-1-yl)-3-{[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](tetrahydro-2H-pyran-4-yl)amino]-1-{4-[(E)-2-phenylethenyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](tetrahydro-2H-pyran-4-yl)amino]-1-{4-[(Z)-2-phenylethenyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(Z)-2-(3-pyrazolyl)ethenyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(E)-2-(3-pyrazolyl)ethenyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-1-[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(E)-2-(tetrahydro-2H-pyran-4-ylethenyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](tetrahydro-2H-pyran-4-yl)amino]-1-{4-[(E)-2-(4-thiazolyl)-ethenyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](tetrahydro-2H-pyran-4-yl)amino]-1-{4-[(Z)-2-(4-thiazolyl)-ethenyl]phenyl}-1H-pyrazole-4-carboxylic acid;
1-((E)-2-tert-Butyl-ethenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino)-1H-pyrazole-4-carboxylic acid;
1-((E)-2-Phenyl-ethenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(4-Methyl-1-cyclohexen-1-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(3-cyclophenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-(1-Methylethyl)[(4-methylidenecyclohexyl)carbonyl]amino}-1-phenyl-1H-pyrazole-4-carboxylic acid;
1-(4-Trifluoromethyl-cyclohexen-1-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-(4-[(phenyloxy)methyl]phenyl}-1H-pyrazole-4-carboxylic acid;
1-[4-(Phenylsulfonylmethyl)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[4-(Phenylthiomethyl)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-4-(Phenoxy)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[4-{(1,3-Thiazol-4-ylmethyl)oxy)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[4-([E]-Phenylethenyl)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[4-[Z]-Phenylethenyl))phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[4-([E,Z]-(1,3-Thiazol-2-yl)ethenyl)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[4-([E]-Phenyl-2-methylethenyl)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[4-[E]-(Pyridin-4-yl)ethenyl))phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[4-([E]-(1,3-Thiazol-4-yl)ethenyl)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[4-([E]-(Furan-2-yl)ethenyl))phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-[4-([E]-(2-Methyl-1,3-thiazol-4-yl)ethenyl)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[(Cyclohexylacetyl)(1-methylethyl)amino]-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-((1-Methylethyl)[(4-methylphenyl)carbonyl]amino}-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-[[(4-Bromo-2-chlorophenyl)carbonyl](1-methylethyl)amino]-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](phenyl)amino]-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-{[2-(Dimethylamino)-2-oxoethyl][(trans-4-methylcyclohexyl)carbonyl-]amino}-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-([(trans-4-Methylcyclohexyl)carbonyl]{1-[(methyloxy)carbonyl]-4-piperidinyl}amino)-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-{[(trans-4-Methylcyclohexyl)carbonyl][1-(methylsulfonyl)-4-piperidinyl]amino}-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-(methyl-4-piperidinyl)amino]-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-{{1-[(Ethylamino)carbonyl]-4-piperidinyl}[(trans-4-methylcyclohexyl)carbonyl]amino}-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](2-pyrazinylmethyl)amino]-1-phenyl-1H-pyrazole-4-carboxylic acid;
rel-3-[{[(1S,2R,4S)-2-Hydroxy-4-methylcyclohexyl]carbonyl}(1-methylethyl)amino]-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(3-methoxyphenylcarbonyl)amino]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(phenylmethyl)oxy]phenyl}-1H-pyrazole-4-carboxylic acid;
1-(1H-indol-5-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(E/Z)-2-phenylethenyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-[4-(2-phenylethyl)phenyl]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexylcarbonyl](tetrahydro-2H-pyran-1-yl)amino]-1-{4-[2phenylethyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[((trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-[4-[(1,3-thiazol-4-yl)ethyl]phenyl]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](tetrahydro-2H-pyran-4-yl)amino]-1-{4-[(1,3-thiazol-4-yl)-ethyl]phenyl}-1H-pyrazole-4-carboxylic acid;
1-Cyclohexyl-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-[1-(methylsulfonyl)-1,2,3,6-tetrahydro-4-pyridinyl)-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](phenylmethyl)amino]-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-{Cyclopentyl[(trans-4-methylcyclohexyl)carbonyl]amino}-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl]-(tetrahydro-2H-pyran-4-yl)amino]-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-{(1-Acetyl-4-piperidinyl)[(trans-4-methylcyclohexyl)carbonyl]amino}-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](4-piperidinyl)amino]-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(E)-2-cyclohexylethenyl]phenyl}-1H-pyrazole-4-carboxylic acid;
1-[4-(2-Cyclohexylethyl)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[2-pyridinylethenyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[2-pyridinylethyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[1,3-thiazol-2-ylethyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[2-(1H-pyrazol-3-yl)ethyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(phenylamino)carbonyl]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(phenylcarbonyl)amino]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(3-methylphenylcarbonyl)amino]phenyl}-1H-pyrazole-4-carboxylic acid;
3-([(trans-4-Methylcyclohexyl)carbonyl]{1-[(tert-butyloxy)carbonyl]-4-piperidinyl}amino)-1-phenyl-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(4-fluorophenylcarbonyl)amino]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(cyclohexylcarbonyl)amino]phenyl}-1H-pyrazole-4-carboxylic acid;
1-(4-{[(4-Fluorophenyl)amino]carbonyl}phenyl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{3-[(chlorophenylcarbonyl)amino]phenyl}-1H-pyrazole-4-carboxylic acid;
3-[[(trans-4-Methylcyclohexyl)carbonyl](1-methylethyl)amino]-1-{4-[(phenylsulfonyl)amino]phenyl}-1H-pyrazole-4-carboxylic acid;
1-(4-Methyl-1-cyclohexen-1-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylic acid;
1-(4,4-Dimethyl-1-cyclohexen-1-yl)-3-[[(trans-4-methylcyclohexyl)carbonyl](tetrahydro-3-furanyl)amino]-1H-pyrazole-4-carboxylic acid
and salts, solvates and esters, and individual enantiomers thereof.

126 more elements

A method of treating or preventing viral infection which comprises administering to a subject in need thereof, an effective amount of a compound of Formula (I)

wherein:
A represents hydroxy;
R1 represents aryl, heteroaryl bonded through a ring carbon atom, or heterocyclyl bonded through a ring carbon atom, each of which may be optionally substituted by one or more substituents selected from —C1-6alkyl, halo, ORA, SRA, —C(O)NRBRC, —C(O)RD, —CO2H, —CO2RD, —NRBRC, —NREC(O)RD, —NRECO2RD, —NREC(O)NRFRG, —SO2NRFRG, —SO2RD, nitro, cyano, —CF3, —OCF3, NRESO2RD, phenyl and heterocyclyl, wherein the —C1-6alkyl substituent itself may be optionally substituted by one or more substituents selected from —C5-9cycloalkyl, halo, —NRBRC, —C(O)NRBRC, —NRE—C(O)RD, —SRA, —SO2RD, ORA, oxo, phenyl, heteroaryl or heterocyclyl;
or R1 represents —C1-6alkyl or —C5-9cycloalkyl;
R2 represents phenyl substituted by one or more substituents selected from —C1-6alkyl, halo, —ORA, —SRA, —C(O)NRBRC, —C(O)RD, —CO2H, —CO2RD, —NRBRC, —NREC(O)RD, —NRECO2RD, —NREC(O)NRFRG, —SO2NRFRG, —SO2RD, nitro, cyano, and heterocyclyl;
or R2 represents —(CH2)nC5-7cycloalkyl optionally substituted on the cycloalkyl by one or more substitutents selected from —C1-6alkyl, —CH(CH2)tH, —ORA, —SRA, —C(O)NRBRC, —C(O)RD, —CO2H, —CO2RD, —NRBRC, —NREC(O)RD, —NR5CO2RD, —NREC(O)NRFRG, —SO2NRFRG, —SO2RD, fluoro, nitro, cyano, oxo, and heterocyclyl, or wherein two substituents may together form a C1-2alkylene bridge substituent;
t represents 0, 1, 2, 3 or 4;
n represents 0 or 1;
R3 represents heterocyclyl or heteroaryl;
or phenyl optionally substituted by one or more substituents selected from —C1-6alkyl, halo, —ORA, —SRA, —C(O)NRBRC, —C(O)RD, —CO2H, —CO2RD, —NRBRC, —NREC(O)RD, —NRECO2RD, —NREC(O)NRFRG, —SO2NRFRG, —SO2RD, nitro, cyano, and heterocyclyl;
or R3 represents —C1-6alkyl optionally substituted by one or more substituents selected from —C1-6alkyl, —ORA, —SRA, —C(O)NRBRC, —C(O)RD, —CO2H, —CO2RD, —NRBRC, —NREC(O)RD, —NRECO2RD, —NREC(O)NRFRG, —SO2NRFRG, —SO2RD, fluoro, nitro, cyano, oxo, phenyl, heteroaryl and heterocyclyl;
R4 represents hydrogen;
RA represents hydrogen, —C1-6alkyl, arylalkyl, heteroarylalkyl, aryl, heterocyclyl or heteroaryl;
RB and RC independently represent hydrogen, —C1-6alkyl, aryl, heterocyclyl or heteroaryl;
or RB and RC together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group;
RD is selected from the group consisting of —C1-6alkyl, aryl, heterocyclyl, heteroaryl, arylalkyl, and heteroarylalkyl;
RE represents hydrogen or —C1-6alkyl;
RF and RG are independently selected from the group consisting of hydrogen, —C1-6alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl;
or RF and RG together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group;
or a pharmaceutically acceptable salt, solvate, or ester thereof.

17 more elements

Dependencies are inferred from the claim text.