Patent ID: 6303637
Filing Date: 2001-10-16
Classification: A61K,A61P,C07D

Abstract:
A compound of structural Formula I: ##STR31##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.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,(9) (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --,(10) [(C.dbd.O)O.sub.r ].sub.s -aryl, wherein aryl is as defined below,(11) aryloxy, wherein aryl is as defined below,(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) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.1 -C.sub.6)-akyl-aryl,(22) hydrogen,(23) OCF.sub.3,(24) [(C.dbd.O)O.sub.r ].sub.s (C.sub.1 -C.sub.6)-alkyl-aryl,(25) S(O).sub.n --NR.sup.8 R.sup.9,(26) (C.sub.1 -C.sub.3)-alky-O--N.dbd.C(CH.sub.3)(aryl), wherein aryl is as defined below, or(27) R.sup.1 and R.sup.2 or R.sup.6 and R.sup.7 can an be taken together when they are on adjacent carbons to form a fused benzo, dihydrofuranyl, furanyl, pyrrolidyl, dihydropyriolidyl, 1,3-dioxolan group, ##STR32##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,(19) (C.sub.1 -C.sub.10)-alkyl, wherein alkyl includes cyclic as well as acyclic groups and is unsubstituted or substituted with one, two or three 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,(p) CONR.sup.8 R.sup.9,(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') (C1-C4)-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') O(C.sub.0 -C.sub.6)-alkyl-phenyl,(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') methylenedioxyl, and(s') OCF.sub.3,(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') (C1-C4)-perfuoroalkyl,(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(r') fused benzo or pyridyl group,(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') (C1-C4)-perfuoroalkyl,(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,(t') thioxo,(u') fused benzo, and(v') fused pyridyl group;(t) benzyl-S(O).sub.n --,(u) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.2 -C.sub.6)-alkeny,(w) O[(C.dbd.O)O.sub.r ].sub.s heteroaryl,(x) O(CH.sub.2).sub.n heteroaryl,(y) O(CH.sub.2).sub.n aryl,(z) fused benzo,(aa) CF.sub.3,(bb) .dbd.N--O-(C.sub.1 -C.sub.6)alkyl-CO.sub.2 -(C.sub.1 -C.sub.3)alkyl,(cc) S(O).sub.n --(C.sub.0 -C.sub.6)alkyl-aryl, wherein aryl is as defined above, or(dd) S(O).sub.n --(C.sub.0 -C.sub.6)alkyl-heteroaryl, wherein heteroaryl is as defined above,(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) heteroaryl, wherein heteroaryl is as defined above,(q) heterocyclyl, wherein heterocyclyl is as defined above,(r) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.1 -C.sub.6)-alkyl, alkyl as defined above,(s) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.2 -C.sub.6)-alkenyl, as defined above,(t) O[(C.dbd.O)O.sub.r ].sub.s aryl, aryl as defined above,(u) O[(C.dbd.O)O.sub.r ].sub.s heteroaryl, heteroaryl as defined above,(v) O(CH.sub.2).sub.n heteroary, heteroaryl as defined above, and(w) 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) bydroxy,(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) heteroaryl, wherein heteroaryl is as defined above,(s) heterocyclyl, wherein heterocyclyl is as defined above,(t) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.1 -C.sub.6)-alkyl, alkyl as defined above,(u) O[(C.dbd.O)O.sub.r ].sub.s (C.sub.2 -C.sub.6)-alkenyl, as defined above,(v) O[(C.dbd.O)O.sub.r ].sub.s aryl, aryl as defined above,(w) O[(C.dbd.O)O.sub.r ].sub.s heteroaryl, heteroaryl as defined above(x) O(CH.sub.2).sub.n heteroaryl, heteroaryl as defined above, and(y) 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) O[(C.dbd.O)O.sub.r ].sub.s heteroaryl, heteroaryl as defined above(26) O(CH.sub.2).sub.n heteroary, heteroaryl as defined above,(27) aryl, wherein aryl is as defined above,(28) O(CH.sub.2).sub.n aryl, aryl as defined above,(29) oxo,(30) .dbd.CH-(C1-C6)-alkyl, wherein alkyl is as defined above,(31) .dbd.CH-(C2-C6)-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.5 is:(1) [(C.dbd.O)O.sub.r ].sub.s (C.sub.2 -C.sub.10)-alkenyl, wherein alkenyl is as defined above,(2) [C(.dbd.O)O](C.sub.1 -C.sub.10)-alkyl, wherein alkyl is substituted with one, two, or three substituents as defined above in R.sup.3 and R.sup.4,(3) (C.dbd.O)(C.sub.1 -C.sub.10)-alkyl, wherein alkyl is substituted with one, two, or three substituents as defined above in R.sup.3 and R.sup.4,(4) (C.sub.1 -C.sub.10)-alkyl, wherein when R.sup.5 is C.sub.4 -alkyl, R.sup.3 and R.sup.4 are not both hydrogen or when R.sup.5 is C.sub.4 -alkyl and one of R.sup.3 or R.sup.4 is methyl, the other R.sup.3 or R.sup.4 is not hydrogen or methyl,(5) hydroxy,(6) [(C.dbd.O)O.sub.r ].sub.s aryl, wherein aryl is as defined above,(7) oxo,(8) (C.dbd.O).sub.r S(O).sub.n (C.sub.1 -C.sub.8)-alkyl, wherein alkyl is as defined above,(9) (C.dbd.O).sub.r S(O).sub.n aryl, wherein aryl is as defined above,(10) (C.dbd.O).sub.r S(O).sub.n heteroayl, wherein heteroarylaryl is as defined above,(11) (C.dbd.O)(C.sub.1 -C.sub.6)-alkyl-pentafluorobenzene, or(12) [(C.dbd.O)O.sub.r ].sub.s heteroaryl, wherein heteroaryl is as defined above;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,or R.sup.8 and R.sup.9 can be linked to make one of the following with the nitrogen to which they are bound: ##STR33##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.