Patent ID: 6211222
Filing Date: 2001-04-03
Classification: A61P,C07D,Y02A

Abstract:
A compound of the formula ##STR16##and pharmaceutically acceptable salts thereof, wherein:R is hydrogen, C.sub.1 -C.sub.6 alkyl, --(CH.sub.2).sub.n (C.sub.3 -C.sub.7 cycloalkyl) wherein n is 0 to 2, (C.sub.1 -C.sub.6 alkoxy)C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, or --(Z').sub.b (Z"").sub.c (C.sub.6 -C.sub.10 aryl) wherein b and c are independently 0 or 1, Z' is C.sub.1 -C.sub.6 alkylene or C.sub.2 -C.sub.6 alkenylene, and Z"" is O, S, SO.sub.2, or NR.sub.9, and wherein said alkyl, alkenyl, alkoxalkyl, and aryl moieties of said R groups are optionally substituted by one or more substituents independently selected from halo, hydroxy, C.sub.1 -C.sub.5 alkyl, C.sub.2 -C.sub.5 alkenyl, C.sub.1 -C.sub.5 alkoxy, C.sub.3 -C.sub.6 cycloalkoxy, trifluoromethyl, nitro, CO.sub.2 R.sub.9, C(O)NR.sub.9 R.sub.10, NR.sub.9 R.sub.10 and SO.sub.2 NR.sub.9 R.sub.10 ;R.sub.1 is hydrogen, C.sub.1 -C.sub.7 alkyl, C.sub.2 -C.sub.3 alkenyl, phenyl, C.sub.3 -C.sub.7 cycloalkyl, or (C.sub.3 -C.sub.7 cycloalkyl)C.sub.1 -C.sub.2 alkyl, wherein said alkyl, alkenyl and phenyl R.sub.1 groups are optionally substituted with up to 3 substituents independently selected from the group consisting of methyl, ethyl, trifluoromethyl, and halo,R.sub.2.sup.a and R.sub.2.sup.b are independently selected from the group consisting essentially of hydrogen and hereinafter recited substituents, provided that one, but not both of R.sub.2.sup.a and R.sub.2.sup.b must be independently selected as hydrogen, wherein said substituents are selected from: ##STR17##wherein the dashed lines in formulas (Ia) and (Ib) independently and optionally represent a single or double bond, provided that in formula (Ia) both dashed lines cannot both represent double bonds at the same time;m is 0 to 4;R.sub.3 is H, halo, cyano, C.sub.2 -C.sub.4 alkynyl optionally mono substituted by phenyl; C.sub.1 -C.sub.4 alkyl optionally substituted by one or more halogens; --CH.sub.2 NHC(O)C(O)NH.sub.2, cyclopropyl optionally substituted by R.sub.11, R.sub.17, CH.sub.2 OR.sub.9, NR.sub.8 R.sub.10, CH.sub.2 NR.sub.9 R.sub.10, (CO.sub.2 R.sub.9, C(O)N.sub.8 R.sub.10, C(O)CR.sub.11, C(Z)H or CH.dbd.CR.sub.11 R.sub.11 ; provided that R.sub.3 is absent when the dashed line In formula (Ia) attached to the ring carbon atom to which R.sub.3 is attached represents a double bond;R.sub.4 is H, R.sub.6, C(Y)R.sub.14, CO.sub.2 R.sub.14, C(Y)NR.sub.17 R.sub.14, CN, C(NR.sub.17)NR.sub.17 R.sub.14, C(NOR.sub.9)R.sub.14, C(O)NR.sub.9 NR.sub.9 C(O)R.sub.9, C(O)NR.sub.8 NR.sub.17 R.sub.14, C(NOR.sub.14)R.sub.9, C(NR.sub.9)NR.sub.17 R.sub.14, C(NR.sub.14)NR.sub.9 R.sub.10, C(NCN)NR.sub.17 R.sub.14, C(NCN)S(C.sub.1 -C.sub.4 alkyl), CR.sub.9 R.sub.10 OR.sub.14, CR.sub.9 R.sub.10 SR.sub.14, CR.sub.9 R.sub.10 S(O).sub.n R.sub.15 wherein n is 0 to 2, CR.sub.8 R.sub.10 NR.sub.14 R.sub.17, CR.sub.9 R.sub.10 NR.sub.17 SO.sub.2 R.sub.15, CR.sub.9 R.sub.10 NR.sub.17 C(Y)R.sub.14, CR.sub.9 R.sub.10 NR.sub.17 CO.sub.2 R.sub.15, CR.sub.8 R.sub.10 NR.sub.17 C(Y)NR.sub.17 R.sub.14, CR.sub.9 R.sub.10 NR.sub.17 C(NCN)NR.sub.17 R.sub.14, CR.sub.9 R.sub.10 NR.sub.17 C(CR.sub.9 NO.sub.2)S(C.sub.1 -C.sub.4 alkyl), CR.sub.9 R.sub.10 CO.sub.2 R.sub.16 ; CR.sub.9 R.sub.10 C(Y)NR.sub.17 R.sub.14, CR.sub.9 R.sub.10 C(NR.sub.17)NR.sub.17 R.sub.14, CR.sub.9 R.sub.10 CN, CR.sub.9 R.sub.10 C(NOR.sub.10)R.sub.14, CR.sub.9 R.sub.10 C(NOR.sub.14)R.sub.10, CR.sub.8 R.sub.10 NR.sub.17 C(NR.sub.17)S(C.sub.1 -C.sub.4 alkyl), CR.sub.9 R.sub.10 NR.sub.17 C(NR.sub.17)NR.sub.17 R.sub.14, CR.sub.9 R.sub.10 NR.sub.17 C(O)C(O)NR.sub.17 R.sub.14, or CR.sub.9 R.sub.10 NR.sub.17 C(O)C(O)OR.sub.14 ;R.sub.5 is R.sub.8, OR.sub.8, CH.sub.2 OR.sub.9, cyano, C(O)R.sub.9, CO.sub.2 R.sub.9, C(O)NR.sub.9 R.sub.10, or NR.sub.9 R.sub.10, provided that R.sub.5 is absent when the dashed line in formula (Ia) represents a double bond;or R.sub.4 and R.sub.5 are taken together to form --O;or R.sub.5 is hydrogen and R.sub.4 is OR.sub.14, SR.sub.14, S(O).sub.n R.sub.16 wherein n is 0 to 2, SO.sub.2 NR.sub.17 R.sub.14, NR.sub.17 R.sub.14, NR.sub.14 C(O)R.sub.9, NR.sub.17 C(Y)R.sub.14, NR.sub.17 C(O)OR.sub.15, NR.sub.17 C(Y)NR.sub.17 R.sub.14, NR.sub.17 SO.sub.2 NR.sub.17 R.sub.14, NR.sub.17 C(NCN)NR.sub.17 R.sub.14, NR.sub.17 SO.sub.2 R.sub.15, NR.sub.17 C(CR.sub.9 NO.sub.2)NR.sub.17 R.sub.14, NR.sub.17 C(NCN)S(C.sub.1 -C.sub.4 alkyl), NR.sub.17 C(CR.sub.9 NO.sub.7)S(C.sub.1 -C.sub.4 alkyl), NR.sub.17 C(NR.sub.17)NR.sub.17 R.sub.14, NR.sub.17 C(O)C(O)NR.sub.17 R.sub.14, or NR.sub.17 C(O)C(O)OR.sub.14 ;R.sub.6 is independently selected from methyl and ethyl optionally substituted by one or more halogens;R.sub.11 is independently fluoro or R.sub.10 ;R.sub.12 is C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.3 alkenyl, C.sub.3 -C.sub.7 cycloalkyl, (C.sub.3 -C.sub.7 cycloalkyl)C.sub.1 -C.sub.2 alkyl, C.sub.6 -C.sub.10 aryl, or C.sub.3 -C.sub.9 heterocyclyl, wherein said R.sub.12 groups are optionally substituted with up to 3 substituents independently selected from the group consisting of methyl, ethyl, trifluoromethyl, and halo;R.sub.13 is hydrogen or R.sub.12 ;R.sub.14 is hydrogen or R.sub.15 ;R.sub.15 is C.sub.1 -C.sub.6 alkyl or --(CR.sub.9 R.sub.10).sub.n R.sub.16 wherein n is 0 to 2 and R.sub.10 and said C.sub.1 -C.sub.9 alkyl are optionally substituted by one or more substituents independently selected from halo, nitro, cyano, NR.sub.10 R.sub.17, C(O)R.sub.9, OR.sub.9, C(O)NR.sub.10 R.sub.17, OC(O)NR.sub.10 N.sub.17, NR.sub.17 C(O)NR.sub.17 R.sub.10, NR.sub.17 C(O)R.sub.10, NR.sub.17 C(O)O(C.sub.1 -C.sub.4 alkyl), C(NR.sub.17)NR.sub.17 R.sub.10, C(NCN)NR.sub.17 R.sub.10, C(NCN)S(C.sub.1 -C.sub.4 alkyl), NR.sub.17 C(NCN)S(C.sub.1 -C.sub.4 alkyl), NR.sub.17 C(NON)NR.sub.17 R.sub.10, NR.sub.17 SO.sub.2 (C.sub.1 -C.sub.4 alkyl), S(O).sub.n (C.sub.1 -C.sub.4 alkyl) wherein n is 0 to 2, NR.sub.17 C(O)C(O)NR.sub.17 R.sub.10, NR.sub.17 C(O)C(o)R.sub.17, or C.sub.1 -C.sub.2 alkyl optionally substituted with one to three flourines;R.sub.16 is C.sub.3 -C.sub.7 cycloalkyl;R.sub.17 is OR.sub.8 or R.sub.10 ;R.sub.18 is H, C(Y)R.sub.14, CO.sub.2 R.sub.14, C(Y)NR.sub.17 R.sub.14, CN, C(NR.sub.17)NR.sub.17 R.sub.14, C(NOR.sub.9)R.sub.14, C(O)NR.sub.9 NR.sub.9 C(O)R.sub.8, C(O)NR.sub.8 NR.sub.17 R.sub.14, C(NOR.sub.14)R.sub.9, C(NR.sub.9)NR.sub.17 R.sub.14, C(NR.sub.14)NR.sub.9 R.sub.10, C(NCN)NR.sub.17 R.sub.14, C(NCN)S(C.sub.1 -C.sub.4 alkyl), CR.sub.8 R.sub.10 OR.sub.14, CR.sub.9 R.sub.10 SR.sub.14, CR.sub.9 R.sub.10 S(O).sub.n R.sub.15 wherein n is 0 to 2, CR.sub.9 R.sub.10 NR.sub.14 R.sub.17, CR.sub.9 R.sub.10 NR.sub.17 SO.sub.2 R.sub.15, CR.sub.9 R.sub.10 NR.sub.17 C(Y)R.sub.14, CR.sub.9 R.sub.10 NR.sub.17 CO.sub.2 R.sub.15, CR.sub.9 R.sub.10 NR.sub.17 C(Y)NR.sub.17 R.sub.14, or CR.sub.9 R.sub.10 NR.sub.17 C(NCN)NR.sub.17 R.sub.14, or CR.sub.9 R.sub.10 NR.sub.17 C(CR.sub.5 NO.sub.2)S(C.sub.1 -C.sub.4 alkyl);R.sub.19 is --C(O)R.sub.14, --C(O)NR.sub.9 R.sub.14, --S(O).sub.2 R.sub.15, or --S(O).sub.2 NR.sub.9 R.sub.14,Y is O or S; and,Z is O, NR.sub.17, NCN, C(--CN).sub.2, CR.sub.9 CN, CR.sub.9 NO.sub.2, CR.sub.9 CO.sub.2 R.sub.9, CR.sub.9 C(O)NR.sub.9 R.sub.10, C(--CN)CO.sub.2 (C.sub.1 -C.sub.4 alkyl) or C(CN)C(O)NR.sub.9 R.sub.10.