Patent ID: 6083980
Filing Date: 2000-07-04
Classification: A61K,C07D

Abstract:
A compound of structural Formula I: ##STR99## or a pharmaceutically acceptable salt, crystal form, or hydrate, wherein: a and b are independently a single bond or a double bond, and represented by ----- in the structure above;n is: 0, 1 or 2;r is: 0 or 1;s is: 0 or 1;R.sup.1 and R.sup.10a are independently:(1) H,(2) .dbd.O, when R.sup.2 is absent or R.sup.10b is absent respectively,(3) (C.sub.1 -C.sub.10)-alkyl, wherein alkyl is unsubstituted or substituted with one or two substituents selected from the group consisting of:(a) halo, wherein halo is fluoro, chloro, bromo, or iodo,(b) hydroxy,(c) oxo,(d) (C.sub.1 -C.sub.6)-alkyloxy,(e) (C.sub.1 -C.sub.6)-S(O).sub.n --,(f) aryl-(C.sub.1 -C.sub.6)-alkyloxy,(g) cyano,(h) nitro,(i) vinyl,(j) NR.sup.4 R.sup.5,(k) NR.sup.4 COC.sub.1 -C.sub.6 -alkyl,(l) CHO,(m) CO.sub.2 H,(n) COC.sub.1 -C.sub.6 -alkyl,(o) CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(p) CONR.sup.4 R.sup.5,(q) aryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted or substituted with one, two or three of the substituents selected from the group consisting of:(a') halo, as defined above,(b') hydroxy,(c') (C.sub.1 -C.sub.6)-alkyl,(d') (C.sub.1 -C.sub.4)-perfluoroalkyl,(e') (C.sub.1 -C.sub.6)-alkenyl,(f') (C.sub.1 -C.sub.6)-alkynyl,(g') (C.sub.1 -C.sub.6)-alkyloxy,(h') (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --,(i') phenyl,(j') phenoxy,(k') cyano,(l') nitro,(m') CO.sub.2 H,(n') COC.sub.1 -C.sub.6 -alkyl,(o') CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(p') CONR.sup.4 R.sup.5,(q') NR.sup.4 R.sup.5,(r') NR.sup.4 COC.sub.1 -C.sub.6 -alkyl,(s') (C.sub.1 -C.sub.6)-alkenyloxy, and(t') benzyloxy;(r) heteroaryl, wherein heteroaryl is defined as an unsubstituted, monosubstituted, or disubstituted five or six membered aromatic heterocycle containing from 1 to 3 heteroatoms selected from the group consisting of O, N and S and wherein the substituents are selected from the group consisting of:(a') halo, as defined above,(b') hydroxy,(c') (C.sub.1 -C.sub.6)-alkyl,(d') (C.sub.1 -C.sub.4)-perfluoroalkyl,(e') (C.sub.1 -C.sub.6)-alkenyl,(f') (C.sub.1 -C.sub.6)-alkynyl,(g') (C.sub.1 -C.sub.6)-alkyloxy,(h') (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --,(i') phenyl,(j') phenoxy,(k') cyano,(l') nitro,(m') CO.sub.2 H,(n') COC.sub.1 -C.sub.6 -alkyl,(o') CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(p') CONR.sup.4 R.sup.5,(q') NR.sup.4 R.sup.5,(r') NR.sup.4 COC.sub.1 -C.sub.6 -alkyl,(s') fused benzo, and(t') fused pyridyl group,(s) heterocyclyl, wherein heterocyclyl is defined as a cyclic, non-aromatic moiety containing from 1 to 3 heteroatoms selected from the group consisting of O, N, and S, said heterocycle being unsubstituted or substituted with one, two or three substituents selected from the group consisting of:(a') halo, as defined above,(b') hydroxy,(c') (C.sub.1 -C.sub.6)-alkyl,(d') (C.sub.1 -C.sub.4)-perfluoroalkyl,(e') (C.sub.1 -C.sub.6)-alkenyl,(f') (C.sub.1 -C.sub.6)-alkynyl,(g') (C.sub.1 -C.sub.6)-alkyloxy,(h') (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --,(i') phenyl,(j') phenoxy,(k') cyano,(l') nitro,(m') CO.sub.2 H,(n') COC.sub.1 -C.sub.6 -alkyl,(o') CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(p') CONR.sup.4 R.sup.5,(q') NR.sup.4 R.sup.5,(r') NR.sup.4 COC.sub.1 -C.sub.6 -alkyl, and(s') oxo,(t') fused benzo, and(u') fused pyridyl group;(4) (C.sub.2 -C.sub.10)-alkenyl, wherein alkenyl is unsubstituted or substituted with one or two substituents selected from the group consisting of:(a) halo, wherein halo is fluoro, chloro, bromo, or iodo,(b) hydroxy,(c) oxo,(d) (C.sub.1 -C.sub.6)-alkyloxy,(e) (C.sub.1 -C.sub.6)-S(O).sub.n --,(f) phenyl-(C.sub.1 -C.sub.6)-alkyloxy,(g) cyano,(h) nitro,(i) vinyl,(j) NR.sup.4 R.sup.5,(k) NR.sup.4 COC.sub.1 -C.sub.6 -alkyl,(l) CHO,(m) CO.sub.2 H,(n) COC.sub.1 -C.sub.6 -alkyl,(o) CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(p) CONR.sup.4 R.sup.5,(q) aryl, wherein aryl is as defined above,(r) heteroaryl, wherein heteroaryl is as defined above, and(s) heterocycle, wherein the heterocycle is as defined above,(5) (C.sub.2 -C.sub.10)-alkynyl, wherein alkynyl is unsubstituted or substituted with one or two substituents selected from the group consisting of:(a) halo, wherein halo is fluoro, chloro, bromo, or iodo,(b) hydroxy,(c) oxo,(d) (C.sub.1 -C.sub.6)-alkyloxy,(e) (C.sub.1 -C.sub.6)-S(O).sub.n --,(f) phenyl-(C.sub.1 -C.sub.6)-alkyloxy,(g) cyano,(h) nitro,(i) vinyl,(j) NR.sup.4 R.sup.5,(k) NR.sup.4 COC.sub.1 -C.sub.6 -alkyl,(l) CHO,(m) CO.sub.2 H,(n) COC.sub.1 -C.sub.6 -alkyl,(o) CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(p) CONR.sup.4 R.sup.5,(q) aryl, wherein aryl is as defined above,(r) heteroaryl, wherein heteroaryl is as defined above,(s) heterocyclyl, wherein heterocyclyl is as defined above, and(t) Si(R.sup.4).sub.3,(6) an exo-methylene group, when R.sup.2 is absent or R.sup.10b is absent respectively; or(7) aryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted or substituted with one, two or three substituents selected from the group consisting of:(a') halo, as defined above,(b') hydroxy,(c') (C.sub.1 -C.sub.6)-alkyl,(d') (C.sub.1 -C.sub.4)-perfluoroalkyl,(e') (C.sub.1 -C.sub.6)-alkenyl,(f') (C.sub.1 -C.sub.6)-alkynyl,(g') (C.sub.1 -C.sub.6)-alkyloxy,(h') (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --,(i') phenyl,(j') phenoxy,(k') cyano,(l') nitro,(m') CO.sub.2 H,(n') COC.sub.1 -C.sub.6 -alkyl,(o') CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(p') CONR.sup.4 R.sup.5,(q') NR.sup.4 R.sup.5,(r') NR.sup.4 COC.sub.1 -C.sub.6 -alkyl,(s') (C.sub.1 -C.sub.6)-alkenyloxy, and(t') benzyloxy;R.sup.2 is:(1) H,(2) absent when R.sup.1 is oxo,(3) absent when R.sup.1 is an exo-methylene group, or(4) OH,R.sup.3 is:(1) H, or(2) (C.sub.1 -C.sub.10)-alkyl, wherein alkyl is unsubstituted or substituted with one or two substituents selected from the group consisting of:(a) halo, wherein halo is fluoro, chloro, bromo, iodo,(b) hydroxy,(c) oxo,(d) (C.sub.1 -C.sub.6)-alkyloxy,(e) (C.sub.1 -C.sub.6)-S(O).sub.n --,(f) aryl-(C.sub.1 -C.sub.6)-alkyloxy,(g) cyano,(h) nitro,(i) vinyl,(j) NR.sup.4 R.sup.5,(k) NR.sup.4 COC.sub.1 -C.sub.6 -alkyl,(l) CHO,(m) CO.sub.2 H,(n) COC.sub.1 -C.sub.6 -alkyl,(o) CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(p) CONR.sup.4 R.sup.5,(q) aryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted or substituted with one, two or three of the substituents selected from the group consisting of:(a') halo, as defined above,(b') hydroxy,(c') (C.sub.1 -C.sub.6)-alkyl,(d') (C.sub.1 -C.sub.4)-perfluoroalkyl,(e') (C.sub.1 -C.sub.6)-alkenyl,(f') (C.sub.1 -C.sub.6)-alkynyl,(g') (C.sub.1 -C.sub.6)-alkyloxy,(h') (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --,(i') phenyl,(j') phenoxy,(k') cyano,(l') nitro,(m') CO.sub.2 H,(n') COC.sub.1 -C.sub.6 -alkyl,(o') CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(p') CONR.sup.4 R.sup.5,(g') NR.sup.4 R.sup.5, and(r') NR.sup.4 COC.sub.1 -C.sub.6 -alkyl,(r) heteroaryl, wherein heteroaryl is defined as an unsubstituted, monosubstituted, or disubstituted five or six membered aromatic heterocycle containing from 1 to 3 heteroatoms selected from the group consisting of O, N and S and wherein the substituents are members selected from the group consisting of:(a') halo, as defined above,(b') hydroxy,(c') (C.sub.1 -C.sub.6)-alkyl,(d') (C.sub.1 -C.sub.4)-perfluoroalkyl,(e') (C.sub.1 -C.sub.6)-alkenyl,(f') (C.sub.1 -C.sub.6)-alkynyl,(g') (C.sub.1 -C.sub.6)-alkyloxy,(h') (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --,(i') phenyl,(j') phenoxy,(k') cyano,(l') nitro,(m') CO.sub.2 H,(n') COC.sub.1 -C.sub.6 -alkyl,(o') CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(p') CONR.sup.4 R.sup.5,(q') NR.sup.4 R.sup.5,(r') NR.sup.4 COC.sub.1 -C.sub.6 -alkyl, and(s') fused benzo or pyridyl group,(s) heterocyclyl, wherein heterocyclyl is defined as a cyclic, non-aromatic moiety containing from 1 to 3 heteroatoms selected from the group consisting of O, N, and S, said heterocycle being unsubstituted or substituted with one, two or three substituents selected from the group consisting of:(a') halo, as defined above,(b') hydroxy,(c') (C.sub.1 -C.sub.6)-alkyl,(d') (C.sub.1 -C.sub.4)-perfluoroalkyl,(e') (C.sub.1 -C.sub.6)-alkenyl,(f') (C.sub.1 -C.sub.6)-alkynyl,(g') (C.sub.1 -C.sub.6)-alkyloxy,(h') (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --,(i') phenyl,(j') phenoxy,(k') cyano,(l') nitro,(m') CO.sub.2 H,(n') COC.sub.1 -C.sub.6 -alkyl,(o') CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(P') CONR.sup.4 R.sup.5,(q') NR.sup.4 R.sup.5,(r') NR.sup.4 COC.sub.1 -C.sub.6 -alkyl, and(s') oxo,(t') fused benzo, and(u') fused pyridyl group;(t) Si(R.sup.4).sub.3,(3) (C.sub.2 -C.sub.10)-alkenyl, wherein alkenyl is unsubstituted or substituted with one or two substituents selected from the group consisting of:(a) halo, wherein halo is fluoro, chloro, bromo, or iodo,(b) hydroxy,(c) oxo,(d) (C.sub.1 -C.sub.6)-alkyloxy,(e) (C.sub.1 -C.sub.6)-S(O).sub.n --,(f) phenyl-(C.sub.1 -C.sub.6)-alkyloxy,(g) cyano,(h) nitro,(i) vinyl,(j) NR.sup.4 R.sup.5,(k) NR.sup.4 COC.sub.1 -C.sub.6 -alkyl,(l) CHO,(m) CO.sub.2 H,(n) COC.sub.1 -C.sub.6 -alkyl,(o) CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(p) CONR.sup.4 R.sup.5,(q) aryl, wherein aryl is as defined above,(r) heteroaryl, wherein heteroaryl is as defined above, and(s) heterocyclyl, wherein heterocyclyl is as defined above;(4) (C.sub.2 -C.sub.10)-alkynyl, wherein alkynyl is unsubstituted or substituted with one or two substituents selected from the group consisting of:(a) halo, wherein halo is fluoro, chloro, bromo, or iodo,(b) hydroxy,(c) oxo,(d) (C.sub.1 -C.sub.6)-alkyloxy,(e) (C.sub.1 -C.sub.6)-S(O).sub.n --,(f) phenyl-(C.sub.1 -C.sub.6)-alkyloxy,(g) cyano,(h) nitro,(i) vinyl,(j) NR.sup.4 R.sup.5,(k) NR.sup.4 COC.sub.1 -C.sub.6 -alkyl,(l) CHO,(m) CO.sub.2 H,(n) COC.sub.1 -C.sub.6 -alkyl,(o) CO.sub.2 C.sub.1 -C.sub.6 -alkyl,(p) CONR.sup.4 R.sup.5,(q) aryl, wherein aryl is as defined above,(r) heteroaryl, wherein heteroaryl is as defined above, and(s) heterocyclyl, wherein heterocyclyl is as defined above; or(5) cyano;R.sup.4 and R.sup.5 are independently:(1) hydrogen,(2) C.sub.1 -C.sub.6 alkyl, or(3) aryl, wherein aryl is defined above,R.sup.6 is:(1) hydrogen,(2) oxo and a is a single bond,(3) O[(C.dbd.O)O.sub.r ].sub.s R.sup.11,(4) O[(C.dbd.O)O.sub.r ].sub.s aryl, aryl as defined above,(5) O[(C.dbd.O)O.sub.r ].sub.s heteroaryl, heteroaryl as defined above,(6) OC(.dbd.O)NR.sup.11 R.sup.12,(7) NR.sup.11 R.sup.12, or(8) absent, when a is a double bond;R.sup.7, R.sup.8 and R.sup.9 are independently selected from the group consisting of:(1) hydrogen,(2) oxo,(3) O[(C.dbd.O)O.sub.r ].sub.s R.sup.11,(4) O[(C.dbd.O)O.sub.r ].sub.s aryl, aryl as defined above,(5) O[(C.dbd.O)O.sub.r ].sub.s heteroaryl, heteroaryl as defined above,(6) OC(.dbd.O) NR.sup.11 R.sup.12, and(7) NR.sup.11 R.sup.12 ;R.sup.10b is:(1) H,(2) absent when R.sup.10a is oxo,(3) an exo-methylene group, when R.sup.2 is absent or R.sup.10b is absent respectively, or(4) OH; andR.sup.11 and R.sup.12 are independently chosen from the group consisting of:(1) H, and(2) (C.sub.1 -C.sub.6)-alkyl, wherein alkyl is unsubstituted or substituted with one, two or three substituents selected from the group consisting of: Br, Cl, F, I, (C.sub.1 -C.sub.6)-alkoxy, vinyl, cyano, oxo, nitro, hydroxy, CHO, CO.sub.2 H, COC.sub.1 -C.sub.6 -alkyl, CO.sub.2 C.sub.1 -C.sub.6 -alkyl, CONR.sup.4 R.sup.5, NR.sup.4 R.sup.5, NR.sup.4 COC.sub.1 -C.sub.6 -alkyl, aryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted or substituted with one, two or three substituents selected from the group consisting of: Br, Cl, F, I, (C.sub.1 -C.sub.6)-alkoxy, phenyl, phenoxy, cyano, oxo, nitro, hydroxy, CHO, CO.sub.2 H, COC.sub.1 -C.sub.6 -alkyl, CO.sub.2 C.sub.1 -C.sub.6 -alkyl, CONR.sup.4 R.sup.5, NR.sup.4 R.sup.5, NR.sup.4 COC.sub.1 -C.sub.6 -alkyl and any two of adjacent substituents can be joined to form a 5-, 6- or 7-membered fused ring said ring containing 1 or 2 oxygen atoms and the remainder carbon atoms, heteroaryl, wherein heteroaryl is defined as a 5 or 6-membered ring substituted with one and two heteroatoms selected from O, S, N, unsubstituted or substituted with one, two or three substituents selected from the group consisting of: Br, Cl, F, I, (C.sub.1 -C.sub.6)-alkoxy, cyano, oxo, nitro, hydroxy, CHO, CO.sub.2 H, COC.sub.1 -C.sub.6 -alkyl, CO.sub.2 C.sub.1 -C.sub.6 -alkyl, CONR.sup.4 R.sup.5, NR.sup.4 R.sup.5, NR.sup.4 COC.sub.1 -C.sub.6 -alkyl, any two adjacent substituents can be joined to form a 5-, 6- or 7-membered fused ring said ring containing 1 or 2 oxygen atoms and the remainder carbon atoms, or any two adjacent substituents can be joined together to form a benzo-fused ring.