Patent ID: 6043226
Filing Date: 2000-03-28
Classification: A61P,C07H

Abstract:
A compound of the formula 1 or 2 ##STR115## or a pharmaceutically acceptable salt or solvate thereof, wherein: X is --CH(--NR.sup.9 R.sup.10)--, --CH(OR.sup.3)--, --C(O)--, --CH.sub.2 NR.sup.6 --, --NR.sup.6 CH.sub.2 --, or --C(.dbd.NR.sup.5)--, wherein the first dash of each of the foregoing X groups is attached to the C-10 carbon of the compounds of formulas 1 and 2 and the last dash of each group is attached to the C-8 carbon of the compounds of formulas 1 and 2; ##STR116## R.sup.1 and R.sup.2 are each OH; or R.sup.2 is O and R.sup.1 is X.sup.2, and they are taken together as follows: ##STR117## wherein X.sup.2 is O, --N(R.sup.7)--, or --N(NR.sup.7 R.sup.8)--; each R.sup.3 and R.sup.3' is independently selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl, --(CH.sub.2).sub.m (C.sub.6 -C.sub.10 aryl), and --(CH.sub.2).sub.m (4-10 membered heterocyclic), wherein m is an integer ranging from 0 to 4 and the foregoing R.sup.3 groups are optionally substituted by 1 to 3 R.sup.13 groups;R.sup.4 is selected from the group of substituents provided in the definition of R.sup.3 or R.sup.4 is --OR.sup.7 ;or R.sup.3 and R.sup.4 are taken together with the carbon to which each is attached to form a ring defined by X.sup.3, X.sup.4 and X.sup.5 as follows ##STR118## wherein X.sup.3 and X.sup.4 are each independently --(CHR.sup.16).sub.n -- wherein n is an integer ranging from 1to 4;X.sup.5 is S, O, --CHR.sup.6 --) or --N(R.sup.6)--;R.sup.5 is hydroxy, C.sub.1 -C.sub.6, alkyl, C.sub.1 -.sub.6 alkoxy, --(CH.sub.2).sub.m (C.sub.6 -C.sub.10 aryl), --(CH.sub.2).sub.m (4-10 membered heterocyclic), or (C.sub.2).sub.m O(CH.sub.2).sub.z OR.sup.7, wherein m is an integer ranging from 0 to 4 and z is an integer ranging from 2 to 6, and the foregoing R.sup.5 groups, except hydroxy, are optionally substituted by 1 to 3 R.sup.13 groups;R.sup.6 is H, hydroxy, formyl, C.sub.1 -C.sub.10 alkoxy, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, --SO.sub.2 (C.sub.1 -C.sub.10 alkyl), --(C.sub.2).sub.m C(O)CH.sub.2 OC(O)(C.sub.1 -C.sub.10 akyl), --(CH.sub.2).sub.m C(O)(CH.sub.2).sub.t NR.sup.11 R.sup.12, --(CH.sub.2).sub.t C(O)(C.sub.1 -C.sub.10 alkyl), --(CH.sub.2).sub.m C(O)(CH.sub.2).sub.t C(O)(C.sub.1 -C.sub.10 alkyl), --(CH.sub.2).sub.m C(O)(CH.sub.2).sub.t O(C.sub.1 -C.sub.10 alkyl), --(CH.sub.2).sub.m C(O)(CH.sub.2).sub.t O(C.sub.2 -C.sub.10 alkenyl), --(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.m C(O)(CH.sub.2).sub.q (C.sub.6 -C.sub.10 aryl), --C(O)(CH.sub.2).sub.m C(O)(CH.sub.2).sub.q (4-10 membered heterocylic), --(CH.sub.2).sub.m C(O)(CH.sub.2).sub.q (C.sub.6 -C.sub.10 aryl), --(CH.sub.2).sub.m C(O)(CH.sub.2).sub.q (4-10 membered heterocyclic), --(CH.sub.2).sub.q C(O)(CH.sub.2).sub.m O(CH.sub.2).sub.t (C.sub.6 -C.sub.10 aryl), --(CH.sub.2).sub.q C(O)(CH.sub.2).sub.m O(CH.sub.2).sub.t (4-10 membered heterocyclic), --(CH.sub.2).sub.t O(CH.sub.2).sub.m (C.sub.6 -C.sub.10 aryl), --(CH.sub.2).sub.t O(CH.sub.2).sub.m (4-10 membered heterocyclic), --(CH.sub.2).sub.m P(O)R.sup.3 R.sup.16, --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), --(CH.sub.2).sub.m C(S)(CH.sub.2).sub.t NR.sup.11 R.sup.12, wherein m is an integer ranging from 0 to 4, q and t are each independently an integer ranging from 0 to 5, the --(CH.sub.2).sub.q -- moiety of the above R.sup.6 groups optionally includes a carbon-carbon double bond where q is 2 or greater, the heterocyclic moieties of the above R.sup.6 groups optionally include an oxo (.dbd.O) group on the ring system, and the foregoing R.sup.6 groups, except H, formyl and hydroxy, are optionally substituted by 1 to 3 R.sup.13 groups;each R.sup.7 and R.sup.8 is independently H or C.sub.1 -C.sub.6 alkyl;R.sup.9 and R.sup.10 are each independently selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl, --C(.dbd.NR.sup.5)NR.sup.7 R.sup.8, and --C(O)R.sup.7, or R.sup.9 and R.sup.10 are taken together to form .dbd.CH(CH.sub.2).sub.m (C.sub.6 -C.sub.10 aryl, .dbd.CH(CH.sub.2).sub.m (4-10 membered heterocyclic), .dbd.CR.sup.7 R.sup.8, or .dbd.C(R.sup.7)C(O)OR.sup.8, wherein m is an integer ranging from 0 to 4, and the alkyl, aryl and heterocyclic moieties of the foregoing R.sup.9 and R.sup.10 groups are optionally substituted by 1 to 3 R.sup.13 groups;R.sup.11 and R.sup.12 are each independently selected from the group consisting of H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, --C(O)(C.sub.1 -C.sub.10 alkyl), --(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 the foregoing R.sup.11 and R.sup.12 groups, except H, are optionally substituted by 1 to 3 R.sup.13 groups;each R.sup.13 is independently selected from the group consisting of halo, cyano, nitro, trifluoromethyl, azido, --C(O)R.sup.16, --C(O)OR.sup.16, --OC(O)R.sup.16, --OC(O)OR.sup.16, --NR.sup.14 C(O)R.sup.15, --C(O)NR.sup.14 R.sup.15, --NR.sup.14 R.sup.15, hydroxy, C.sub.1 -C.sub.6 alkyl, --N(SO.sub.2 R.sup.16).sub.2, --NR.sup.14 SO.sub.2 R.sup.16, --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 (4-10 membered heterocyclic), wherein m is an integer ranging from 0 to 4, and the alkyl, alkoxy, aryl and heterocyclic moieties of the above R.sup.13 subsituents are optionally substituted by 1 to 3 substituents independently selected from the group consisting of halo, cyano, nitro, trifluoromethyl, azido, --C(O)R.sup.16, --C(O)OR.sup.16, --CO(O)R.sup.16, --OC(O)OR.sup.16, --NR.sup.14 C(O)R.sup.15, --C (O)NR.sup.14 R.sup.15,--NR.sup.14 R.sup.15, hydroxy C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;each R.sup.14 and R.sup.15 is independently H, --OR.sup.7, 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 m is an integer ranging from 0 to 4, with the proviso that where R.sup.14 and R.sup.15 are both attached to the same nitrogen, then R.sup.14 and R.sup.15 are not both --OR.sup.7 ;each R.sup.16 is independently selected from the group consisting of 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 heterocyclic), wherein m is an integer ranging from 0 to 4; and,R.sup.17 is selected from the group of substituents provided in the definition of R.sup.18 or R.sup.17 is a group of the formula ##STR119## R.sup.18 is --CR.sup.3 .dbd.CR.sup.3' R.sup.4 or a group of the formula ##STR120## wherein the dashed line represents an optional double bond; and R.sup.19 is ethyl, an alpha-branched C.sub.3 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, (C.sub.1 -C.sub.6 alkoxy)C.sub.1 -C.sub.6 alkyl, (C.sub.1 -C.sub.6 alkylthio)C.sub.1 -C.sub.6 alkyl, (C.sub.5 -C.sub.8 cycloalkyl)(C.sub.2 -C.sub.5 alpha branched a alkyl)-, C.sub.3 -C.sub.8 cycloalkyl, C.sub.5 -C.sub.8 cycloalkenyl, 3-6 membered O or S containing heterocyclic group, or phenyl, wherein each of the foregoing R.sup.19 groups may be substituted by 1 to 3 substituents independently selected from hydroxy, halo and C.sub.1 -C.sub.4 alkyl.