Patent ID: 6194458
Filing Date: 2001-02-27
Classification: A61K,A61P,C07C,C07D

Abstract:
A compound of structural Formula I: ##STR65##or a pharmaceutically acceptable salt, crystal form, or hydrate, wherein:n is: 0, 1, 2 or 3;r is: 0 or 1;s is: 0 or 1;R.sup.1, R.sup.2, R.sup.5, R.sup.6 and R.sup.7 are independently:(1) halo, wherein halo is fluoro, chloro, bromo, or iodo,(2) hydroxy,(3) (C.sub.1 -C.sub.6)-alkyl,(4) HO(C.sub.1 -C.sub.6)-alkyloxy,(5) (C.sub.1 -C.sub.4)-perfluoroalkyl,(6) (C.sub.2 -C.sub.6)-alkenyl,(7) (C.sub.2 -C.sub.6)-alkynyl,(8) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.1 -C.sub.6)-alkyl, wherein the alkyl may be cyclic or straight-chained,(9) (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --,(10) phenyl,(11) phenoxy,(12) cyano,(13) nitro,(14) CO.sub.2 H,(15) CO(C.sub.1 -C.sub.6)-alkyl,(16) CO.sub.2 (C.sub.1 -C.sub.6)-alkyl,(17) CONR.sup.8 R.sup.9,(18) NR.sup.8 R.sup.9,(20) (C.sub.2 -C.sub.6)-alkenyloxy,(21) benzyloxy,(22) hydrogen, or(23) OCF.sub.3 ;R.sup.3 and R.sup.4 are independently:(1) halo, wherein halo is fluoro, chloro, bromo, or iodo,(2) hydroxy,(3) HO(C.sub.1 -C.sub.6)-alkyloxy,(4) (C.sub.1 -C.sub.4)-perfluoroalkyl,(5) O(CO)CCl.sub.3,(6) (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --,(7) phenyl-(CH.sub.2).sub.r -S(O).sub.n --,(8) cyano,(9) nitro,(10) CO.sub.2 H,(11) CO(C.sub.1 -C.sub.6)-alkyl,(12) CO.sub.2 (C.sub.1 -C.sub.6)-alkyl,(13) CONR.sup.8 R.sup.9,(14) NR.sup.8 R.sup.9,(15) O(CO)NR.sup.8 R.sup.9,(16) azido,(17) NR.sup.8 (CO)NR.sup.8 R.sup.9,(18) hydrogen, provided that both R.sup.3 and R.sup.4 are not hydrogen,(19) (C.sub.1 -C.sub.10)-alkyl, wherein the alkyl is cyclic or acyclic and is unsubstituted or substituted with one or two of the substituents selected from the group consisting of:(a) halo, wherein halo is fluoro, chloro, bromo, or iodo,(b) hydroxy,(c) oxo,(d) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.1 -C.sub.6)-alkyl,(e) (C.sub.1 -C.sub.6)alkyl-S(O).sub.n --,(f) aryl-(C.sub.1 -C.sub.6)-alkyloxy,(g) cyano,(h) nitro,(i) vinyl,(j) NR.sup.8 R.sup.9,(k) O(CO)NR.sup.8 R.sup.9,(l) CHO,(m) CO.sub.2 H,(n) CO(C.sub.1 -C.sub.6)-alkyl,(o) CO.sub.2 (C.sub.1 -C.sub.6)-alkyl, wherein alkyl may be substituted with phenyl,(p) CONR.sup.8 R.sup.9,(q) aryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted orsubstituted 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.2 -C.sub.6)-alkenyl,(f') (C.sub.2 -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') CO(C.sub.1 -C.sub.6)-alkyl,(o') CO.sub.2 (C.sub.1 -C.sub.6)-alkyl,(p') CONR.sup.8 R.sup.9,(q') NR.sup.8 R.sup.9, and(s) heterocyclyl, wherein heterocyclyl is defined as a 3 to 7 atom cyclic, non-aromatic substituent 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.2 -C.sub.6)-alkenyl,(f') (C.sub.2 -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') CO(C.sub.1 -C.sub.6)-alkyl,(o') CO.sub.2 (C.sub.1 -C.sub.6)-alkyl,(p') CONR.sup.8 R.sup.9,(q') NR.sup.8 R.sup.9,(r') NR.sup.8 CO(C.sub.1 -C.sub.6)-alkyl,(s') oxo, and(t') fused benzo,(t) benzyl-S(O).sub.n --,(u) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.2 -C.sub.6)-alkenyl,(v) O[(C.dbd.O)O.sub.r ].sub.s aryl, or(w) O(CH.sub.2).sub.n aryl;(20) (C.sub.2 -C.sub.10)-alkenyl, wherein alkenyl is unsubstituted or substituted with one or two of the substituents selected from the group consisting of:(a) halo, wherein halo is fluoro, chloro, bromo, or iodo,(b) hydroxy,(c) oxo,(e) (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --,(f) phenyl-(C.sub.1 -C.sub.6)-alkyloxy,(g) cyano,(h) nitro,(i) NR.sup.8 R.sup.9,(j) CHO,(k) CO.sub.2 H,(l) CO(C.sub.1 -C.sub.6)-alkyl,(m) CO.sub.2 (C.sub.1 -C.sub.6)-alkyl,(n) CONR.sup.8 R.sup.9,(o) aryl, wherein aryl is as defined above,(p) heterocyclyl, wherein heterocyclyl is as defined above,(q) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.1 -C.sub.6)-alkyl, alkyl as defined above,(r) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.2 -C.sub.6)-alkenyl, as defined above,(s) O[(C.dbd.O)O.sub.r ].sub.s aryl, aryl as defined above, and(t) O(CH.sub.2).sub.n aryl, aryl as defined above;(21) (C.sub.2 -C.sub.10)-alkynyl, wherein alkynyl is unsubstituted or substituted with one or two of the 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.8 R.sup.9,(k) NR.sup.8 CO(C.sub.1 -C.sub.6)-alkyl,(l) CHO,(m) CO.sub.2 H,(n) CO(C.sub.1 -C.sub.6)-alkyl,(o) CO.sub.2 C(C.sub.1 -C.sub.6)-alkyl,(p) CONR.sup.8 R.sup.9,(q) aryl, wherein aryl is as defined above,(r) heterocyclyl, wherein heterocyclyl is as defined above,(s) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.1 -C.sub.6)-alkyl, alkyl as defined above,(t) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.2 -C.sub.6)-alkenyl, as defined above,(u) O[(C.dbd.O)O.sub.r ].sub.s aryl, aryl as defined above,(v) O(CH.sub.2).sub.n aryl, aryl as defined above,(22) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.1 -C.sub.6)-alkyl, alkyl as defined above,(23) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.2 -C.sub.6)-alkenyl, as defined above,(24) O[(C.dbd.O)O.sub.r ].sub.s aryl, aryl as defined above,(25) aryl, wherein aryl is as defined above or(26) O(CH.sub.2).sub.n aryl, aryl as defined above;R.sup.3 can also be any of the following when R.sup.4 is absent:(29) oxo,(30) .dbd.CH-(C.sub.1 -C.sub.6)-alkyl, wherein alkyl is as defined above,(31) .dbd.CH-(C.sub.2 -C.sub.6)-alkenyl, wherein alkenyl is as defined above,(32) .dbd.CH-aryl, wherein aryl is as defined above, or(33) .dbd.CH.sub.2 ;R.sup.8 and R.sup.9 are independently selected from the group consisting of:(1) hydrogen,(2) [(C.dbd.O)O.sub.r ].sub.s aryl, wherein aryl is as defined above,(3) [(C.dbd.O)O.sub.r ].sub.s (C.sub.2 -C.sub.8)-alkenyl, wherein alkenyl is as defined above,(4) [(C.dbd.O)O.sub.r ].sub.s (C.sub.1 -C.sub.8)-alkyl, wherein alkyl is as defined above,(5) (C.dbd.O).sub.r S(O).sub.n (C.sub.1 -C.sub.8)-alkyl, wherein alkyl is as defined above,(6) (C.dbd.O).sub.r S(O).sub.n -aryl, wherein aryl is as defined above, and(7) heterocyclyl, wherein heterocyclyl is defined above;R.sup.10 is:(1) hydrogen,(2) [(C.dbd.O)O.sub.r ].sub.s aryl, wherein aryl is as defined above, or(3) [(C.dbd.O)O.sub.r ].sub.s (C.sub.1 -C.sub.6)-alkyl, wherein alkyl is as defined above.