Patent ID: 6410562
Filing Date: 2002-06-25
Classification: C07D

Abstract:
A compound of Formula (I): whereinX is â€”Oâ€”, â€”Sâ€”, or â€”NR5â€”; R5 is hydrogen, C1-8 alkyl, or an amino protecting group; R1, R1â€², R2, and R3 are independently hydrogen or C1-8 alkyl; R1 and R2 optionally together form a bond and R1â€² and R3 are independently hydrogen or C1-8 alkyl; R1 and R2 optionally combine together with the carbon atoms to which they are attached form a C3-7 carbocyclic ring and R1â€² and R3 are independently hydrogen or C1-8 alkyl; R1 and R1â€² together with the carbon atom to which they are attached optionally combine to form a C3-7 spirocarbocyclic ring and R2 and R3 are independently hydrogen or C1-8 alkyl; R2 and R3 together with the carbon atom to which they are attached optionally combine to form a C3-7 spirocarbocyclic and R1 and R1â€² are independently hydrogen or C1-8 alkyl; n is 0, 1, or 2; m is 0, 1 or 2; mâ€² is 0, 1, or 2; qâ€² is 0,1,2,3,4, or 5; R4 is Y is â€”Oâ€”, â€”Sâ€”, or â€”NR8â€”; Yâ€² is â€”Oâ€” or â€”Sâ€”; R6 and R7 are independently hydrogen, C1-8 alkyl, C3-7 cycloalkyl, C1-8 alkoxy, C1-8 alkylthio, halo C1-8 alkylthio, C1-8 alkylsulfinyl, C1-8 alkylsulfonyl, C3-7 cycloalkoxy, aryl-C1-8 alkoxy, halo, halo-C1-8 alkyl, halo-C1-8 alkoxy, nitro, â€”NR10R11, â€”CONR10R11, aryl C1-8 alkyl, optionally substituted heterocyclyl, optionally substituted phenyl, optionally substituted naphthyl, optionally halo substituted acylamino, cyano, hydroxy, COR12, halo C1-8 alkylsulfinyl, or halo C1-8 alkylsulfonyl, or alkoxyalkyl of the formula CH3(CH2)pâ€”Oâ€”(CH2)qâ€”Oâ€”; â€ƒwhere p is 0, 1, 2, 3, or 4; and q is 1, 2, 3, 4, or 5; R12 is C1-8 alkyl or optionally substituted phenyl; R8 is hydrogen, C1-8 alkyl, halo-C1-8 alkyl, optionally substituted phenyl, optionally substituted heterocyclyl, COO C1-8 alkyl, optionally substituted COaryl, COC1-8 alkyl, SO2C1-8 alkyl, optionally substituted SO2 aryl, optionally substituted phenyl-C1-8 alkyl, CH3(CH2)pâ€”Oâ€”(CH2)qâ€”Oâ€”; R9 is hydrogen, halo, C1-8 alkyl, halo C1-8 alkyl, C1-8 alkylthio, halo C1-8 alkylthio, C3-7 cycloalkylthio, optionally substituted arylthio or heteroarylthio, C1-8 alkoxy, C3-7 cycloalkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, or optionally substituted aryl or heteroaryl, C3-7 cycloalkyl, halo C3-7 cycloalkyl, C3-7 cycloalkenyl, cyano, COOR10,CONR10R11 or NR10R11, C2-6 alkenyl, optionally substituted heterocyclyl, optionally substituted aryl C1-8 alkyl, optionally substituted heteroaryl C1-8 alkyl in which the alkyl group can be substituted by hydroxy, or C1-8 alkyl substituted by hydroxy, R10 and R11 are independently hydrogen, C1-8 alkyl, optionally substituted aryl C1-8 alkyl, optionally substituted phenyl, or R10 and R11 together with the nitrogen atom to which they are attached may combine to form a ring with up to six carbon atoms which optionally may be substituted with up to two C1-8 alkyl groups or one carbon atom may be replaced by oxygen or sulfur; R14 and R16 are independently hydrogen, halo, C1-8 alkyl, C3-7 cycloalkyl, C3-7 cycloalkoxy, C3-7 cycloalkylC1-8 alkoxy, halo-C1-8 alkyl, halo-C1-8 alkoxy, C1-8 alkoxy, carbo(C1-8)alkoxy, optionally substituted aryl, or optionally substituted heteroaryl; R15 and R17 are independently hydrogen, halo, C1-8 alkoxy, C3-7-cycloalkyl, C3-7 cycloalkylC1-8 alkoxy, C1-8 alkyl, C3-7 cycloalkoxy, hydroxy, halo C1-8 alkoxy, carbo(C1-8)alkoxy, optionally substituted phenyl, optionally substituted phenyl-C1-8 alkyl, optionally substituted phenyloxy, optionally substituted phenyl-C1-8 alkoxy, (tetrahydropyran-2-yl)methoxy, C1-8 alkyl-S(O)mâ€”, optionally substituted aryl-C1-8 alkyl-S(O)mâ€²â€”, CH3(CH2)pâ€”Z1â€”(CH2)qâ€”Z2â€”, or Z3â€”(CH2)qâ€²â€”Z2â€”; Z1 and Z2 are independently a bond, O, S, SO, SO2, sulphoximino, or NR10; and Z3 is hydroxy, protected hydroxy, NR10R11, protected amino, SH or protected SH; provided that when R4 is and Y is O or S, then R7 is hydrogen, R6 is hydrogen, halo, C1-6 alkyl, or halo C1-6 alkyl; andR9 is C1-6 alkyl or optionally substituted phenyl; further provided that when R4 is and Y is â€”NR8â€” then R1, R1â€², R2 and R3 are hydrogen or methyl;X is â€”NHâ€”; n is 0, 1 or 2; R4 is R6 is chloro, fluoro, methyl, trifluoromethyl, or pentafluoroethyl; R7 is hydrogen or chloro, and most preferably hydrogen; R8 is hydrogen; and R9 is hydrogen, methyl, benzyl, 3-chlorobenzyl, 4-chlorophenyl, 3-chlorophenyl, 2-chlorophenyl, 3-methylphenyl, 4-chloro-3-methylphenyl, 4-methoxyphenyl, or 2-methoxyphenyl; further provided that when R4 is and Yâ€² is O, then R7 is hydrogen, R9 is hydrogen, and R6 is hydrogen, halo, C1-6 alkyl, or optionally substituted phenyl, naphthyl, or thienyl;further provided that when R4 is and Yâ€² is S then R7 is hydrogen, R6is hydrogen halo, C1-6 alkyl, halo C1-6 alkyl, C1-6 alkoxy; andR9 is hydrogen, halo, C1-4 alkoxy, C1-4 alkyl, optionally substituted phenyl, naphthyl, or thienyl, or an optionally substituted phenylmethyl, optionally substituted naphthylmethyl, optionally substituted thienylmethyl, or optionally substituted pyridylmethyl group in which the methyl group is substituted by hydroxy; Further provided that when R4 is then R4 is R14 is hydrogen, halo, C1-4 alkyl, C1-4 alkoxy, or halo C1-4 alkyl; and R16 is C1-4 alkyl, halo C1-4 alkyl, or optionally substituted phenyl; or a pharmaceutically acceptable salt or ester thereof.