Patent ID: 6372743
Filing Date: 2002-04-16
Classification: A61P,C07D,G01N

Abstract:
A compound of the formula or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein:X is N or CR14; R1 is selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cyano, halo, C1-C6 haloalkyl, OR7, C1-C6 alkyl-OR7; C1-C6 cyanoalkyl, NR8R9, C1-C6 alkyl-NR8R9; R2 is H, C1-C6 alkyl which optionally forms a C3-C6 aminocarbocycle or a C2-C5 aminoheterocycle with A or B, each of which is optionally substituted with R7, C3-C10 cycloalkyl, or (C3-C10 cycloalkyl) C1-C6 alkyl; or R2 and R6 jointly with the 2 nitrogen atoms to which they are bound, form a C2-C5 aminoheterocycle optionally substituted with R7, or R2 and A jointly form a C3-C6 aminocarbocycle or a C2-C5 aminoheterocycle optionally substituted with R7; A represents an alkyl chain of 1, 2, or 3 carbon atoms which is optionally mono- or di-substituted at each carbon with substituents independently selected from C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, cyano, halo, C1-C6 haloalkyl, OR7, C1-C6 alkyl-OR7; C1-C6 cyanoalkyl, NR8R9, and C1-C6 alkyl-NR8R9; or A and B jointly form a C3-C6 carbocycle, optionally substituted at each atom with R7; B represents an alkyl chain of 1, 2 or 3 carbons atoms, which is optionally mono- or di-substituted at each carbon with substituents independently selected from C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cyano, halo, C1-C6 haloalkyl, OR7, C1-C6 alkyl-OR7; C1-C6 cyanoalkyl, NR8R9, and C1-C6 alkyl-NR8R9; or B and R2 jointly form a C3-C6 aminocarbocycle , which is optionally substituted at each atom with R7; or B and R6 jointly form a C3-C6 aminocarbocycle, which is optionally substituted at each atom with R7; R3 is selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cyano, halo, C1-C6 haloalkyl, OR7, C1-C6 alkyl-OR7, C1-C6 cyanoalkyl, NR8R9, C1-C6 alkyl-NR8R9; R4 is selected from aryl or heteroaryl, each of which is substituted with 1 to 5 substituents independently selected from C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, halogen, C1-C6 haloalkyl, OR7, C1-C6 alkyl-OR7, NR8R9, C1-C6 alkyl-NR8R9, CONR8R9, C1-C6 alkyl-CONR8R9, COOR7, C1-C6 alkyl-COOR7, CN, C1-C6 alkyl-CN, SO2NR8R9, SO2R7, aryl, heteroaryl, heterocycloalkyl, 3-, 4-, or 5-(2-oxo-1,3-oxazolidinyl), wherein at least one of the positions ortho or para to the point of attachment of the aryl or heteroaryl ring to the pyrazole is substituted; R5 is selected from: C1-C6 alkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, each of which is substituted with 1 to 5 groups independently selected at each occurrence from halo, C1-C2 haloalkyl, oxo, OR7, cyano, NR8R9, CONR8R9, COOR7, SO2NR8R9, SO2R7, NR11COR12, NR11SO2R7; or Aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, aryl(C5-C8)cycloalkyl, or heteroaryl(C5-C8)cycloalkyl, each of which is optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C6 alkenyl, halogen, C1-C6 haloalkyl, OR7, NR8R9, C1-C6 alkyl-OR7, C1-C6 alky-NR8R9, CONR8R9, COOR7, CN, SO2NR8R9, SO2R7, aryl, heteroaryl, heterocycloalkyl, 3-, 4-, or 5-(2-oxo-1,3-oxazolidinyl), wherein any 2 adjacent substituents may be take together to form a C3-C10 cycloalkyl ring, a C3-C10 cycloalkenyl ring or a heterocycloalkyl ring; or an unsubstituted C2-C9 heterocycloalkyl containing one, two or three O, S, or N atoms; or C3-C10 cycloalkyl or C2-C9 heterocycloalkyl containing one, two, or three O, S, or N atoms, each of which is substituted with 1 to 6 substituents independently selected from C1-C6 alkyl, C3-C10, cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C6 alkenyl, oxo, halogen, C1-C6 haloalkyl, OR7, NR8R9, (with the proviso that when two OR7 or NR8R9 substituents are geminally located on the same carbon R7 is not H and the geminally located OR7 or NR8R9 substituents can be taken together to form a C2-C4 ketal, oxazoline, oxazolidine, imidazoline, or imidazolidine heterocycle), C1-C6 alkyl-OR7, C1-C6 alkyl-NR8R9, CONR8R9, COOR7, CN, oxo, hydroximino, C1-C6 alkoximino, SO2NR8R9, SO2R7, heterocycloalkyl, aryl, heteroaryl, where aryl or heteroaryl is optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C6 alkenyl, halogen, C1-C6 haloalkyl, OR7, NR8R9, C1-C6 alkyl-OR7, C1-C6 alkyl-NR8R9, COOR7, CN, SO2NR8R9, SO2R7, aryl, heteroaryl, heterocycloalkyl, 3-, 4-, or 5-(2-oxo-1,3-oxazolidinyl), with the proviso that 2 adjacent substituents can optionally form together a C3-C10 cycloalkyl ring, a C3-C10 cycloalkenyl ring or a heterocycloalkyl ring; or aryl or heteroaryl, optionally substituted with 1 to 5 substituents independently selected at each occurrence from halogen, C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C6 alkenyl, halogen, C1-C6 haloalkyl, OR7, NR8R9, C1-C6 alkyl-OR7, C1-C6 alkyl-NR8R9, CONR8R9, COOR7, CN, SO2NR8R9, SO2R7, aryl, heteroaryl, heterocycloalkyl, 3-, 4-, or 5-(2-oxo-1,3-oxazolidinyl), wherein any 2 adjacent substituents may be taken together to form a C3-C10 cycloalkyl ring, a C3-C10 cycloalkenyl ring or a heterocycloalkyl ring; or 3- or 4-piperidinyl, 3-pyrrolidinyl, 3- or 4- tetrahydropyranyl, 3-tetrahydrofuranyl, 3- or 4- tetrahydropyranyl, 3-tetrahydrofuranyl, 3- or 4-tetrahydrothiopyranyl, 3- or 4-(1,1-dioxo) tetrahydrothiopyranyl, 1-azabicyclo[4.4.0]decyl, 8-azabicyclo[3.2.1]octanyl, norbornyl, quinuclidinyl, indolin-2-one-3-yl, 2-(methoximino)-perhydroazepin-6-yl, each optionally substituted with 1 to 5 substituents independently selected at each occurrence from R7, C1-C6 alkyl-OR7, C1-C6 alkyl-NR8R9, CONR8R9, CN, COOR7 SO2NR8R9, and SO2R7; R6 is selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C4 alkenyl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl each of which is optionally substituted with 1 to 5 substituents independently from halogen, C1-C6 haloalkyl, OR13, NR8R9, C1-C6 alkyl-OR13, C1-C6 alkyl-NR8R9, CONR8R9, COOR7, CN, SO2NR8R9, and SO2R7; R7 is independently selected at each occurrence from H, C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C3 haloalkyl, or heterocycloalkyl, C1-C8 alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, C1-C8 alkanoyl, aroyl, heteroaroyl, aryl, heteroaryl, C1-C6 arylalkyl or C1-C6 heteroarylalkyl each optionally substituted with 1 to 5 substituents independently selected from halogen, C1-C6 haloalkyl, OR13, NR8R9, C1-C6 alkyl-OR13, C1-C6 alkyl-NR8R9, CONR8R9, COOR13, CN, SO2NR8R9, and SO2R13, with the proviso that when R7 is SO2R13 cannot be H; R8 and R9 are independently selected at each occurrence from H, C1-C6 alkyl, C3-C10 cycloalkyl, C2-C6 alkenyl, C3-C10 cycloalkenyl, C2-C6 alkynyl, heterocyclkyl C1-C8 alkanoyl, aryl, heteroaroyl, aryl, heteroaryl, C1-C6 arylalkyl or C1-C6 heteroarylalkyl, or R8 and R9, taken together, can form a C3-C6 aminocarbocycle or a C2-C5 aminoheterocycle each of which is optionally substituted with C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C1-C3 haloalkyl, or heterocycloalkyl, C1-C8 alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, C1-C8 alkanoyl, aryl, heteroaroyl, aroyl, heteroaryl, C1-C6 arylalkyl or C1-C6 heteroarylalkyl; R11 is selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl; R12 is selected from H, aryl, heteroaryl, C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, optionally substituted with OR7, NR8R9, C3-C6 aminocarbocycle, or C2-C5 aminoheterocycle; R13 is independently selected at each occurrence from H, C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, with the proviso that when R7 is SO2R13, R13 cannot be H; and R14 is H, C1-C6 alkyl, C3-C10 cycloalkyl, (C3-C10 cycloalkyl) C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, halo, or CN.