Patent ID: 6270768
Filing Date: 2001-08-07
Classification: A61K,A61P,C07H,Y02P

Abstract:
A compound of Formula 1: ##STR17##or a pharmaceutically acceptable salt or solvates thereof, wherein:X is --N(R.sup.a)CH.sub.2 --, wherein the first dash of each of the foregoing X 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, and R.sup.a 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), and --(CH.sub.2).sub.m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4;R.sup.1 is straight-chain or alpha-branched C.sub.1 -C.sub.8 alkyl, alkenyl, alkynyl, alkoxyalkyl or alkylthioalkyl group any of which may be substituted by one or more hydroxyl groups; a C.sub.3 -C.sub.8 cycloalkyl or C.sub.5 -C.sub.8 cycloalkenyl group, either of which may 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 be substituted by one or more C.sub.1 -C.sub.4 alkyl groups or halo atoms or a group of the formula SR.sup.b, wherein R.sup.b is C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.5 -C.sub.8 cycloalkenyl, phenyl or substituted phenyl wherein the substituent is C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy or halo or a 3 to 6 membered oxygen or sulfur containing heterocyclic ring which may be saturated, or fully or partially unsaturated and which may be substituted by one or more C.sub.1 -C.sub.4 alkyl groups or halo atoms;or R.sup.1 is phenyl which may be 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;or R.sup.1 is of the formula ##STR18##wherein Z.sup.1 is O, S or --CH.sub.2 --, and a, b, c, and d is each independently an integer ranging from0 to 2 and a+b+c+d#5;R.sup.2 is H or OH;R.sup.3 is H or --C(O)NR.sup.c R.sup.d, wherein each of R.sup.c and R.sup.d is independently H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.20 alkenyl, C.sub.2 -C.sub.10 alkynyl, --(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 each of the foregoing R.sup.c and R.sup.d groups, except H, may be substituted by 1 to 3 Q groups; or wherein R.sup.c and R.sup.d 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 may include 1 or 2 heteroatoms selected from O, S and N, in addition to the nitrogen to which R.sup.c and R.sup.d are attached, and said saturated ring may include 1 or 2 carbon-carbon double or triple bonds, and said saturated and heteroaryl rings may be substituted by 1 to 3 Q groups;or R.sup.2 and R.sup.3 taken together form a carbonate ring;R.sup.4 is H, OH, O(C.sub.1 -C.sub.10 alkyl);R.sup.5 is H, --C(O)R.sup.e, --C(O)OR.sup.e, --C(O)NR.sup.e R.sup.f, or a hydroxy protecting group, and R.sup.e and R.sup.f is each independently H or C.sub.1 -C.sub.6 alkyl;R.sup.6 is H or OH;R.sup.7 is H or OH;R.sup.8 is C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.20 alkenyl, C.sub.2 -C.sub.10 alkynyl, cyano, --CH.sub.2 S(O).sub.n R.sup.g wherein n is an integer ranging from 0 to 2, --CH.sub.2 OR.sup.g, --CH.sub.2 N(OR.sup.h)R.sup.g, --CH.sub.2 NR.sup.g R.sup.i, --(CH.sub.2).sub.m (C.sub.6 -C.sub.12 aryl), or --(CH.sub.2).sub.m (5-10 membered heteroalkyl), wherein m is an integer ranging from 0 to 4, and wherein the foregoing R.sup.8 groups may be substituted by 1 to 3 Q groups;each R.sup.g 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.q CR.sup.g(1) R.sup.g(2) (CH.sub.2).sub.r NR.sup.g(3) R.sup.g(4) wherein q and r is each independently an integer ranging from 0 to 3 except q and r are not both 0, --(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 foregoing R.sup.g groups, except H, may be substituted by 1 to 3 Q groups;each of R.sup.g(1), R.sup.g(2), R.sup.3(3) and R.sup.g(4) is independently selected from H, C.sub.1 -C.sub.10 alkyl, --(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 foregoing R.sup.g(1), R.sup.g(2), R.sup.g(3) and R.sup.g(4) groups, except H, may be substituted by 1 to 3 Q groups;or R.sup.g(1) and R.sup.g(3) are taken together to form --(CH.sub.2).sub.p -- wherein p is an integer ranging from 0 to 3 such that a 4-7 membered saturated ring is formed that may include 1 or 2 carbon-carbon double or triple bonds;or R.sup.g(3) and R.sup.g(4) are taken together to form a 4-10 membered monocyclic or polycyclic saturated ring or a 5-10 membered heteroaryl ring, wherein said saturated and heteroaryl rings may include 1 or 2 heteroatoms selected from O, S and N, in addition to the nitrogen to which R.sup.g(3) and R.sup.g(4) are attached, said saturated ring may include 1 or 2 carbon-carbon double or triple bonds, and said saturated and heteroaryl rings may be substituted by 1 to 3 Q groups;R.sup.h is H or C.sub.1 -C.sub.6 alkyl;R.sup.i is H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, or C.sub.2 -C.sub.10 alkynyl, wherein the foregoing R.sup.i group may be substituted by 1 to 3 substituents independently selected from halo, OH, and O(C.sub.1 -C.sub.6 alkyl);and if R.sup.8 is --CH.sub.2 NR.sup.g R.sup.i, then R.sup.g and R.sup.i may be taken together to form a 4-10 membered saturated monocyclic or polycycic saturated ring or a 5-10 membered heteroaryl ring, wherein said saturated and heteroaryl rings may include 1 or 2 heteroatoms selected from O, S and N, in addition to the nitrogen to which R.sup.g and R.sup.i are attached, said saturated ring may include 1 or 2 carbon-carbon double or triple bonds, and said saturated and heteroaryl rings may be substituted by 1 to 3 Q groups;or R.sup.7 and R.sup.8 are taken together to form an oxazolyl ring as shown below ##STR19##wherein Z.sup.2 is --SR.sup.g, --(CH.sub.2).sub.n C(O)R.sup.g wherein n is 0 or 1, 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), or --(CH.sub.2).sub.m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4, and wherein the foregoing Z.sup.2 groups may be substituted by 1 to 3 Q groups;each Q is independently selected from halo, cyano, nitro, trifluoromethyl, azido, --C(O)Q.sup.1, --OC(O)Q.sup.1, --C(O)OQ.sup.1, --OC(O)OQ.sup.1, --NQ.sup.2 C(O)Q.sup.3, --C(O)NQ.sup.2 Q.sup.3, --NQ.sup.2 Q.sup.3, hydoxy, C.sub.1 -C.sub.6 alkyl, 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, and wherein said aryl and heteroaryl substituents may be substituted by 1 or 2 subsfituents independently selected from halo, cyano, nitro, trifluoromethyl, azide, --C(O)Q.sup.1, --C(O)OQ.sup.1, --OC(O)OQ.sup.1, --NQ.sup.2 C(O)Q.sup.3, --C(O)NQ.sup.2 Q.sup.3, --NQ.sup.2 Q.sup.3, hydroxy, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;each Q.sup.1, Q.sup.2 and Q.sup.3 is independently selected from H, OH, C.sub.1 -C.sub.10 alkyl, C.sub.1 -C.sub.6 alkoxy, 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), and --(CH.sub.2).sub.m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4;R.sup.9 is H or CH.sub.3 ; andR.sup.10 is H or CH.sub.3.