Patent ID: 6043227
Filing Date: 2000-03-28
Classification: A61P,C07H,Y02P

Abstract:
A compound of the formula ##STR23## or a pharmaceutically acceptable salts thereof, wherein: X is --CH.sub.2 NR.sup.7 --, or --NR.sup.7 CH.sub.2 -- wherein the first dash of each of the foregoing X groups is attached to C-10 carbon of the compound of formula 1 and the last dash of each group is attached to the C-8 carbon of the compound of formula 1;R.sup.1 is hydroxy;R.sup.2 is H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 -alkenyl, C.sub.2 -C.sub.10 alkynyl, cyano, --CH.sub.2 S(O).sub.n R.sup.8 wherein n is an integer ranging from 0 to 2, --CH.sub.2 R.sup.8, --CH.sub.2 ONR.sup.8 R.sup.9, --(CH.sub.2).sub.m (C.sub.6 -C.sub.10 aryl), or --(CH.sub.2).sub.m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4, and wherein the alkyl, alkenyl, alkynyl, aryl and heteroaryl moieties of the foregoing R.sup.1 groups are optionally substituted by 1 to 3 substituents independently selected from the groups consisting of halo, cyano, nitro, trifluoromethyl, azido, --C(O)R.sup.8, --OC(O)R.sup.8, --NR.sup.8 C(O)R.sup.9, --C(O)NR.sup.8 R.sup.9, --NR.sup.8 R.sup.9, hydroxy C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.6 -C.sub.10 aryl, and 5-10 membered heteroaryl;R.sup.3 is an C.sub.2 -C.sub.8 alkyl, alkenyl, alkynyl, alkoxyalkyl or alkylthioalkyl group any of which may optionally be substituted by one or more hydroxyl groups; a C.sub.5 -C.sub.8 cycloalkylalkyl group wherein the alkyl group is an alpha-branched C.sub.2 -C.sub.5 alkyl group; a C.sub.3 -C.sub.8 cycloalkyl or C.sub.5 -C.sub.8 cycloalkenyl group, either of which may optionally be substituted by methyl or one or more hydroxyl or one or more C.sub.1 -C.sub.4 alkyl groups or halo atoms; or a 3 to 6 membered oxygen or sulphur containing heterocyclic ring which may be saturated, or fully or partially unsaturated and which may optionally be substituted by one or more C.sub.1 -C.sub.4 alkyl groups or halo atoms;Or R.sup.3 is phenyl which may be optionally substituted with at least one substituent selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy and C.sub.1 -C.sub.4 alkylthio groups, halogen atoms, hydroxyl groups, trifluoromethyl, and cyano;R.sup.4 is H or a hydroxy protecting group;each R.sup.5 and R.sup.6 is independently H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl, --(CH.sub.2).sub.m C.sub.6 -C.sub.10 aryl, --(CH.sub.2).sub.m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4, and wherein the alkyl, alkenyl, aryl, heteroaryl and alkynyl moieties of the foregoing R.sup.5 and R.sup.6 groups are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, cyano, nitro, trifluoromethyl, azido, --C(O)R.sup.8, --OC(O)R.sup.8, --NR.sup.8 C(O)R.sup.9, --C(O)NR.sup.8 R.sup.9, --NR.sup.8 R.sup.9, hydroxy, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.6 -C.sub.10 aryl, and 5-10 membered heteroaryl; or R.sup.5 and R.sup.6 may be taken together to form a 4-7 membered saturated ring or a 5-10 membered heteroaryl ring, wherein said saturated and heteroaryl rings optionally include 1 or 2 heteroatoms selected from O, S, and N, in addition to the nitrogen to which R.sup.5 and R.sup.6 are attached, said saturated ring optionally includes 1 or 2 carbon-carbon double or triple bonds, and said saturated and heteroaryl rings are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, cyano, nitro, trifluoromethyl, azido, --C(O)R.sup.8, --OC(O)R.sup.8, --NR.sup.8 C(O)R.sup.9, --C(O)NR.sup.8 R.sup.9, --NR.sup.8 R.sup.9, hydroxy, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.6 -C.sub.10 aryl, and 5-10 membered heteroaryl;R.sup.7 is H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl, --(CH.sub.2).sub.m C.sub.6 -C.sub.10 aryl, --(CH.sub.2).sub.m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4, and wherein the alkyl, alkenyl, aryl, heteroaryl and alkynyl moieties of the foregoing R.sup.5 and R.sup.6 groups are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, cyano, nitro, trifluoromethyl, azido, --C(O)R.sup.8, --OC(O)R.sup.8, --NR.sup.8 C(O)R.sup.9, --C(O)NR.sup.8 R.sup.9, --NR.sup.8 R.sup.9, hydroxy, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.6 -C.sub.10 aryl, and 5-10 membered heteroaryl;each R.sup.8 and R.sup.9 is independently H, hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, (CH.sub.2).sub.m (C.sub.6 -C.sub.10 ) aryl, (CH.sub.2).sub.m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4, or C.sub.2 -C.sub.10 alkylyl; and Me is methyl.