Patent ID: 6262066
Filing Date: 2001-07-17
Classification: A61K,A61P

Abstract:
A compound represented by the formula ##STR764##or a pharmaceutically acceptable salt or solvate thereof, wherein:the dotted line represents an optional double bond formed by one of X.sup.1 or X.sup.2 with the carbon to which R.sup.3 is attached;X.sup.1 is R.sup.5 --(C.sub.1 -C.sub.12)alkyl, R.sup.6 --(C.sub.3 -C.sub.12)cycloalkyl, R.sup.7 -aryl, R.sup.8 -heteroaryl or R.sup.10 --(C.sub.3 -C.sub.7)heterocycloalkyl;X.sup.2 is --CHO, --CN, --NHC(.dbd.NR.sup.26)NHR.sup.26, --CH(.dbd.NOR.sup.26), --NHOR.sup.26, R.sup.7 -aryl, R.sup.7 -aryl(C.sub.1 -C.sub.6)alkyl, R.sup.7 -aryl(C.sub.1 -C.sub.6)alkenyl, R.sup.7 -aryl(C.sub.1 -C.sub.6)-alkynyl, --(CH.sub.2).sub.v OR.sup.13, --(CH.sub.2).sub.v COOR.sup.27, --(CH.sub.2).sub.v CONR.sup.14 R.sup.15, --(CH.sub.2).sub.v NR.sup.21 R.sup.22 or --(CH.sub.2).sub.v NHC(O)R.sup.21, wherein v is zero, 1, 2 or 3 and wherein q is 1 to 3 and a is 1 or 2;or X.sup.1 is ##STR765##and X.sup.2 is hydrogen;(R.sup.1 and R.sup.4) or (R.sup.2 and R.sup.3) or (R.sup.1 and R.sup.3) or (R.sup.2 and R.sup.4) together from an alkylene bridge of 1 to 3 carbon atoms with the proviso that R.sup.1, R.sup.2, R.sup.3, R.sup.4 that are not part of the alkylene bridge, are independently selected from hydrogen and (C.sub.1 -C.sub.6)alkyl;R.sup.5 is 1 to 3 substituents independently selected from the group consisting of H, R.sup.7 -aryl, R.sup.6 --(C.sub.3 -C.sub.12)cycloalkyl, R.sup.8 -heteroaryl, R.sup.10 --(C.sub.3 -C.sub.7)heterocycloalkyl, --NR.sup.19 R.sup.20, --OR.sup.13 and --S(O).sub.0-2 R.sup.13 ;R.sup.6 is 1 to 3 substituents independently selected from the group consisting of H, (C.sub.1 -C.sub.6)alkyl, R.sup.7 -aryl, --NR.sup.19 R.sup.20, --OR.sup.13 and --SR.sup.13 ;R.sup.7 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halo, (C.sub.1 -C.sub.6)alkyl, R.sup.25 -aryl, (C.sub.3 -C.sub.12)cycloalkyl, --CN, --CF.sub.3, --OR.sup.19, --(C.sub.1 -C.sub.6)alkyl-OR.sup.19, --OCF.sub.3, --NR.sup.19 R.sup.20, --(C.sub.1 -C.sub.6)alkyl-NR.sup.19 R.sup.20, --NHSO.sub.2 R.sup.19, --SO.sub.2 N(R.sup.26).sub.2, --SO.sub.2 R.sup.19, --SOR.sup.19, --SR.sup.19, --NO.sub.2, --CONR.sup.19 R.sup.20, --NR.sup.20 COR.sup.19, --COR.sup.19, --COCF.sub.3, --OCOR.sup.19, --OCO.sub.2 R.sup.19, --COOR.sup.19, --(C.sub.1 -C.sub.6)alkyl-NHCOOC(CH.sub.3).sub.3, --(C.sub.1 -C.sub.6)alkyl-NHCOCF.sub.3, --(C.sub.1 -C.sub.6)alkyl-NHSO.sub.2 --(C.sub.1 -C.sub.6)alkyl, --(C.sub.1 -C.sub.6)alkyl-NHCONH--(C.sub.1 -C.sub.6)-alkyl or ##STR766##wherein f is 0 to 6; or R.sup.7 substituents on adjacent ring carbon atoms may together form a methylenedioxy or ethylenedioxy ring;R.sup.8 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halo, (C.sub.1 -C.sub.6)alkyl, R.sup.25 -aryl, (C.sub.3 -C.sub.12)cycloalkyl, --CN, --CF.sub.3, --OR.sup.19, --(C.sub.1 -C.sub.6)alkyl-OR.sup.19, --OCF.sub.3, --NR.sup.19 R.sup.20, --(C.sub.1 -C.sub.6)alkyl-NR.sup.19 R.sup.20, --NHSO.sub.2 R.sup.19, --SO.sub.2 N(R.sup.26).sub.2, --NO.sub.2, --CONR.sup.19 R.sup.20, --NR.sup.20 COR.sup.19, --COR.sup.19, --OCOR.sup.19, --OCO.sub.2 R.sup.19 and --COOR.sup.19 ;R.sup.9 is hydrogen, (C.sub.1 -C.sub.6)alkyl, halo, --OR.sup.19, --NR.sup.19 R.sup.20, --NHCN, --SR.sup.19 or --(C.sub.1 -C.sub.6)alkyl-NR.sup.19 R.sup.20 ;R.sup.10 is H, (C.sub.1 -C.sub.6)alkyl, --OR.sup.19, --(C.sub.1 -C.sub.6)alkyl-OR.sup.19, --NR.sup.19 R.sup.20 or --(C.sub.1 -C.sub.6)alkyl-NR.sup.19 R.sup.20 ;R.sup.11 is independently selected from the group consisting of H, R.sup.5 --(C.sub.1 -C.sub.6)alkyl, R.sup.6 --(C.sub.3 -C.sub.12)cycloalkyl, --(C.sub.1 -C.sub.6)alkyl(C.sub.3 -C.sub.12)cycloalkyl, --(C.sub.1 -C.sub.6)alkyl-OR.sup.19, --(C.sub.1 -C.sub.6)alkyl-NR.sup.19 R.sup.20 and ##STR767##wherein q and a are as defined above;R.sup.12 is H, (C.sub.1 -C.sub.6)alkyl, halo, --NO.sub.2, --CF.sub.3, --OCF.sub.3, --OR.sup.19, --(C.sub.1 -C.sub.6)alkyl-OR.sup.19, --NR.sup.19 R.sup.20 or --(C.sub.1 -C.sub.6)alkyl-NR.sup.19 R.sup.20 ;R.sup.13 is H, (C.sub.1 -C.sub.6)alkyl, R.sup.7 -aryl, --(C.sub.1 -C.sub.6)alkyl-OR.sup.19, --(C.sub.1 -C.sub.6)alkyl-NR.sup.19 R.sup.20 or --(C.sub.1 -C.sub.6)alkyl-SR.sup.19 ;R.sup.14 and R.sup.15 are independently selected from the group consisting of H, R.sup.5 --(C.sub.1 -C.sub.6)alkyl, R.sup.7 -aryl and ##STR768##wherein q and a are as defined above;R.sup.19 and R.sup.20 are independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.3 -C.sub.12)cycloalkyl, aryl and aryl(C.sub.1 -C.sub.6)alkyl;R.sup.21 and R.sup.22 are independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.3 -C.sub.12)cycloalkyl, (C.sub.3 -C.sub.12)cycloalkyl(C.sub.1 -C.sub.6)alkyl, (C.sub.3 -C.sub.7)heterocycloalkyl, --(C.sub.1 -C.sub.6)alkyl(C.sub.3 -C.sub.7)-heterocycloalkyl, R.sup.7 -aryl, R.sup.7 -aryl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -heteroaryl(C.sub.1 -C.sub.12)alkyl, --(C.sub.1 -C.sub.6)alkyl-OR.sup.19, --(C.sub.1 -C.sub.6)alkyl-NR.sup.19 R.sup.20, --(C.sub.1 -C.sub.6)alkyl-SR.sup.19, --(C.sub.1 -C.sub.6)alkyl-NR.sup.18 --(C.sub.1 -C.sub.6)alkyl-O--(C.sub.1 -C.sub.6)alkyl and --(C.sub.1 -C.sub.6)alkyl-NR.sup.18 --(C.sub.1 -C.sub.6)alkyl-NR.sup.18 --(C.sub.1 -C.sub.6)alkyl;R.sup.18 is hydrogen or (C.sub.1 -C.sub.6)alkyl;Z.sup.1 is R.sup.7 -aryl;Z.sup.2 is R.sup.7 -aryl or (C.sub.2 -C.sub.6)alkyl;Z.sup.3 is hydrogen or (C.sub.1 -C.sub.6)alkyl;R.sup.25 is 1-3 substituents independently selected from the group consisting of H, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy and halo;R.sup.26 is independently selected from the group consisting of H, (C.sub.1 -C.sub.6)alkyl and R.sup.25 --C.sub.6 H.sub.4 --CH.sub.2 --;R.sup.27 is H, (C.sub.1 -C.sub.6)alkyl, R.sup.7 -aryl(C.sub.1 -C.sub.6)alkyl, or (C.sub.3 -C.sub.12)cycloalkyl; andprovided that when X.sup.1 is ##STR769##and Z.sup.1 is R.sup.7 -phenyl, Z.sup.2 is not (C.sub.2 -C.sub.3)alkyl.