Patent ID: 6300316
Filing Date: 2001-10-09
Classification: A61P,C07D,C07H

Abstract:
A compound of the formula ##STR89##and pharmaceutically acceptable salts thereof, wherein:X.sup.1 is --CH(--NR.sup.18 R.sup.19)--, --C(O)-- or --C(.dbd.NR.sup.5)--, wherein the first dash of each of the foregoing X.sup.1 groups is attached to the 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 and R.sup.2 are each independently OH;or R.sup.2 is O and R.sup.1 is X.sup.2, and they are taken together as follows: ##STR90##wherein X.sup.2 is O, --N(R.sup.9)--, or --N(NR.sup.9 R.sup.10)--;or R.sup.1 is oxo, OH, or --NR.sup.9 R.sup.10, R.sup.2 is O and X.sup.1 is --CH(--O)--, and R.sup.2 and X.sup.1 are taken together as follows: ##STR91##or R.sup.1 is N, R.sup.2 is O, X.sup.1 is --C(.dbd.N)-- or --CH(--NR.sup.9)--, and R.sup.1 is taken together with both R.sup.2 and X.sup.1 as follows: ##STR92##or R.sup.1 is O and X.sup.1 is --C(--NR.sup.9)--, and they are taken together as follows: ##STR93##wherein X.sup.3 is H, C.sub.1 -C.sub.6 alkyl, or --(CH.sub.2).sub.m O(C.sub.1 -C.sub.6 alkyl) wherein m is an integer ranging from 1 to 4 and the alkyl moieties of the foregoing X.sup.3 groups are optionally substituted by 1 or 2 substituents independently selected from halo, --NR.sup.9 R.sup.10 and --OR.sup.9 ;R.sup.3 is hydroxy or methoxy;R.sup.4 is --(CH.sub.2).sub.n NR.sup.8 R.sup.15 wherein n is an integer ranging from 0 to 6 and said R.sup.4 group is optionally substituted by 1 to 3 R.sup.16 groups, with the proviso that n is not 0 when R.sup.8 is --C(O)(C.sub.1 -C.sub.10 alkyl), --C(O)(CH.sub.2).sub.t (C.sub.6 -C.sub.10 aryl), or --C(O)(CH.sub.2).sub.t (4-10 membered heterocyclic);R.sup.5 is hydroxy, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, --(CH.sub.2).sub.m (C.sub.6 -aryl), --(CH.sub.2).sub.m (4-10 membered heterocyclic), or --(CH.sub.2).sub.m O(CH.sub.2).sub.z OR.sup.9, wherein mn is an integer ranging from 0 to 4 and z is an integer ranging from 1 to 6, and the foregoing R.sup.5 groups, except hydroxy, are optionally substituted by 1 to 3 R.sup.16 groups;each R.sup.6 and R.sup.7 is independently H, --OR.sup.9, C.sub.1 -C.sub.6 alkyl, --(CH.sub.2).sub.m (C.sub.6 -C.sub.10 aryl), or --(CH.sub.2).sub.m (4-10 membered heterocyclic), wherein mn is an integer ranging from 0 to 4, with the proviso that when R.sup.6 and R.sup.7 are both attached to the same nitrogen as --NR.sup.6 R.sup.7, then R.sup.6 and R.sup.7 are not both --OR.sup.9 ;R.sup.8 is C.sub.1 alkyl, --C(O)(C.sub.1 -C.sub.10 alkyl), --(CH.sub.2).sub.q CR.sup.11 R.sup.12 (CH.sub.2).sub.r NR.sup.13 R.sup.14 wherein q and r are each independently an integer ranging from 0 to 4 except that q and r are not both 0, --(CH.sub.2).sub.t (C.sub.6 -C.sub.10 aryl), --(CH.sub.2).sub.t (4-10 membered heterocyclic), --C(O)(CH.sub.2).sub.t (C.sub.6 -C.sub.10 aryl), --(CH.sub.2).sub.t O(CH.sub.2).sub.j (C.sub.6 -C.sub.10 aryl), --C(O)(CH.sub.2).sub.t (4-10 membered heterocyclic), --SO.sub.2 (CH.sub.2).sub.t (C.sub.6 -C.sub.10 aryl), or --SO.sub.2 (CH.sub.2).sub.t (4-10 membered heterocyclic), wherein j is an integer ranging from 0 to 2, t is an integer ranging from 0 to 5, the --(CH.sub.2).sub.t -- moieties of the foregoing R.sup.8 groups optionally include a carbon-carbon double or triple bond when t is an integer between 2 and 5, and the foregoing R.sup.8 groups are optionally substituted by 1 to 3 R.sup.16 groups, with the proviso that when X.sup.1 is C.dbd.O, R.sup.8 cannot be C.sub.1 -C.sub.10 alkyl or --C(O)(CH.sub.2).sub.t (C.sub.6 -C.sub.10 aryl);or R.sup.15 and R.sup.8 may be taken together with the nitrogen to which each is attached to form a 4-10 membered saturated monocyclic or polycyclic 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(R.sup.6)-- in addition to the nitrogen to which R.sup.15 and R.sup.8 are attached, said --N(R.sup.6)-- is optionally .dbd.N-- or --N.dbd. when R.sup.15 and R.sup.8 are taken together as said heteroaryl group, said saturated ring optionally may be partially unsaturated by including 1 or 2 carbon-carbon double bonds, and said saturated and heteroaryl rings, including the R.sup.6 group of said --N(R.sup.6)--, are optionally substituted by 1 to 3 R.sup.16 groups;or R.sup.15 and R.sup.8 may be taken together with the nitrogen to which each is attached to form a polycyclic moiety of the formula ##STR94##wherein v is 0 or 1, X.sup.4 is --C(O)--, --CH(OH)--, --(CH.sub.2).sub.m --, --N(R.sup.6)(CH.sub.2).sub.m --, (CH.sub.2).sub.m N(R.sup.6)-- or --(CH.sub.2).sub.m O-- wherein m is an integer ranging from 0 to 2, and X.sup.6 is --(CH.sub.2).sub.w -- wherein w is 1 or 2, --CH.sub.2 O--, --OCH.sub.2 --, --CH.sub.2 N(R.sup.9)--, or --N(R.sup.9)CH.sub.2 --; ##STR95##wherein X.sup.5 is --CH.dbd.CH--, --S--, or --N(R.sup.6)--, and the above groups of formulas 2, 3, and 4, including the Z portions of said groups, are optionally substituted by 1 to 3 R.sup.16 groups; each R.sup.9 and R.sup.10 is independently H or C.sub.1 -C.sub.6 alkyl;each R.sup.11, R.sup.12, R.sup.13 and R.sup.14 is independently selected from H, C.sub.1 -C.sub.10 alkyl, C.sub.1 -C.sub.10 alkanoyl, --(CH.sub.2).sub.m (C.sub.6 -C.sub.10 aryl), --C(O)(CH.sub.2).sub.m (C.sub.6 -C.sub.10 aryl), --(CH.sub.2).sub.m (4-10 membered heterocyclic), and --C(O)(CH.sub.2).sub.m (4-10 membered heterocyclic), wherein m is an integer ranging from 0 to 4, and wherein the foregoing R.sup.11, R.sup.12, R.sup.13 and R.sup.14 groups, except H, are optionally substituted by 1 to 3 R.sup.16 groups;or R.sup.11 and R.sup.13 are taken together to form --(CH.sub.2).sub.p -- wherein p is an integer ranging from 0 to 3 and r+p equals at least 2, such that a 4-9 membered saturated ring is formed that optionally may be partially unsaturated by including 1 or 2 carbon-carbon double bonds;or R.sup.13 and R.sup.14 are taken together with the nitrogen to which each is attached to form a 4-10 membered monocyclic or polycyclic 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(R.sup.6)--, in addition to the nitrogen to which R.sup.13 and R.sup.14 are attached, said --N(R.sup.6)-- is optionally .dbd.N-- or --N.dbd. when R.sup.13 and R.sup.14 are taken together as said heteroaryl group, said saturated ring optionally may be partially unsaturated by including 1 or 2 carbon-carbon double bonds, and said saturated and heteroaryl rings, including the R.sup.6 group of said --N(R.sup.6)--, are optionally substituted by 1 to 3 R.sup.16 groups;or R.sup.13 and R.sup.14 are taken together to form .dbd.C(--NR.sup.9 R.sup.6)NR.sup.10 R.sup.7 ;or R.sup.13 is H and R.sup.14 is --C(.dbd.NR.sup.6)NR.sup.9 R.sup.7 ;R.sup.15 is H or C.sub.1 -C.sub.10 alkyl, wherein the alkyl is optionally substituted by 1 to 3 R.sup.16 groups;each R.sup.16 is independently selected from halo, cyano, nitro, trifluoromethyl, azido, --C(O)R.sup.17, --C(O)OR.sup.17, --OC(O)R.sup.17, --OC(O)OR.sup.17, --NR.sup.6 C(O)R.sup.7, --C(O)NR.sup.6 R.sup.7, --NR.sup.6 R.sup.7, hydroxy, C.sub.1 -C.sub.6 alkyl, --S(O).sub.j (C.sub.1 -C.sub.6 alkyl) wherein j is an integer ranging from 0 to 2, C.sub.1 -C.sub.6 alkoxy, --(CH.sub.2).sub.m (C.sub.6 -C.sub.10 aryl), and --(CH.sub.2).sub.m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4, said alkoxy group is optionally substituted by 1 to 3 groups selected from --NR.sup.9 R.sup.10, halo, and --OR.sup.9, and said aryl and heteroaryl substituents are optionally substituted by 1 to 5 substituents independently selected from halo, cyano, nitro, trifluoromethyl, azido, --C(O)R.sup.17, --C(O)OR.sup.17, --CO(O)R.sup.17, --OC(O)OR.sup.17, --NR.sup.6 C(O)R.sup.7, --C(O)NR.sup.6 R.sup.7, --NR.sup.6 R.sup.7, hydroxy, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;each R.sup.17 is independently selected from H, C.sub.1 -C.sub.10 alkyl, --(CH.sub.2).sub.m (C.sub.6 -C.sub.10 aryl), and --(CH.sub.2).sub.m (4-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4;R.sup.18 and R.sup.19 are each independently selected from H, C.sub.1 -C.sub.6 alkyl, --C(.dbd.NR.sup.5)NR.sup.9 R.sup.10, and --C(O)R.sup.9, or R.sup.18 and R.sup.19 are taken together to form .dbd.CH(CR.sup.9 R.sup.10).sub.m (C.sub.6 -C.sub.10 aryl), .dbd.CH(CR.sup.9 R.sup.10).sub.m (4-10 membered heterocyclic), .dbd.CR.sup.9 R.sup.10, or .dbd.C(R.sup.9)C(O)OR.sup.9, wherein m is an integer ranging from 0 to 4, and wherein the alkyl, aryl and heterocyclic moieties of the foregoing R.sup.18 and R.sup.19 groups are optionally substituted by 1 to 3 R.sup.16 groups;R.sup.20 is H or --C(O)R.sup.9.