Patent ID: 6028181
Filing Date: 2000-02-22
Classification: A61P,C07H,Y02P

Abstract:
A compound, having the formula, ##STR49## or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein either,Y and Z taken together define a group X,whereinX is selected from the group consisting of(1) .dbd.O,(2) .dbd.N--OH,(3) .dbd.N--O--R.sup.1 where R.sup.1 is selected from the group consisting of(a) unsubstituted C.sub.1 -C.sub.12 -alkyl,(b) C.sub.1 -C.sub.12 -alkyl substituted with aryl,(c) C.sub.1 -C.sub.12 -alkyl substituted with substituted aryl,(d) C.sub.1 -C.sub.12 -alkyl substituted with heteroaryl,(e) C.sub.1 -C.sub.12 -alkyl substituted with substituted heteroaryl,(f) C.sub.3 -C.sub.12 -cycloalkyl, and(g) --Si--(R.sup.2)(R.sup.3)(R.sup.4) wherein R.sup.2, R.sup.3 and R.sup.4 are each independently selected from C.sub.1 -C.sub.12 -alkyl and aryl, and(4) .dbd.N--O--C(R.sup.5)(R.sup.6)--O--R.sup.1 where R.sup.1 is as previously defined and R.sup.5 and R.sup.6 are each independently selected from the group consisting of(a) hydrogen,(b) unsubstituted C.sub.1 -C.sub.12 -alkyl,(c) C.sub.1 -C.sub.12 -alkyl substituted with aryl,(d) C.sub.1 -C.sub.12 -alkyl substituted with substituted aryl,(e) C.sub.1 -C.sub.12 -alkyl substituted with heteroaryl, and(f) C.sub.1 -C.sub.12 -alkyl substituted with substituted heteroaryl, orR.sup.5 and R.sup.6 taken together with the atom to which they are attached form a C.sub.3 -C.sub.12 -cycloalkyl ring; or,one of Y and Z is hydrogen and the other is selected from a group consisting of(1) hydrogen,(2) hydroxy,(3) protected hydroxy, and(4) NR.sup.7 R.sup.8 wherein R.sup.7 and R.sup.8 are independently selected from hydrogen and C.sub.1 -C.sub.6 -alkyl, or R.sup.7 and R.sup.8 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring which, when the ring is a 5- to 7-membered ring, may optionally contain a hetero function selected from the group consisting of --O--, --NH--, --N(C.sub.1 -C.sub.6 -alkyl-)--, --N(aryl)--, --N(aryl-C.sub.1 -C.sub.6 -alkyl-)--, --N(substituted-aryl-C.sub.1 -C.sub.6 -alkyl-)--, --N(heteroaryl)--, --N(heteroaryl-C.sub.1 -C.sub.6 -alkyl-)--, --N(substituted-heteroaryl-C.sub.1 -C.sub.6 -alkyl-)--, and --S-- or --S(O).sub.n --, wherein n is 1 or 2,R.sup.a is hydrogen or hydroxy;R.sup.c is hydrogen or a hydroxy protecting group;R is selected from the group consisting of(1) methyl substituted with a moiety selected from the group consisting of(a) CN,(b) F, Cl(c) nitro,(d) --CHO(e) --OR.sup.9 wherein R.sup.9 is selected from the group consisting of:(i) hydrogen(ii) C.sub.1 -C.sub.6 -alkyl, optionally substituted with a substituent selected from the group consisting of(aa) aryl,(bb) substituted-aryl,(cc) heteroaryl, and(dd) substituted-heteroaryl,(iii) aryl,(iv) substituted-aryl,(v) heteroaryl,(vi) substituted-heteroaryl, and(vii) heterocycloalkyl,(f) --C(O).sub.l R.sup.10 wherein l is 1 or 2 and R.sup.10 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.3 -alkyl, C.sub.1 -C.sub.3 -alkyl substituted with aryl, and C.sub.1 -C.sub.3 -alkyl substituted with heteroaryl,(g) S(O).sub.n R.sup.9 where n is 0, 1 or 2 and R.sup.9 is as previously defined,(h) NHC(O)R.sup.10 wherein R.sup.10 is as previously defined,(i) NHC(O)NR.sup.11 R.sup.12 wherein R.sup.11 and R.sup.12 are independently selected from hydrogen, C.sub.1 -C.sub.3 -alkyl, C.sub.1 -C.sub.3 -alkyl substituted with aryl, substituted aryl, heteroaryl, substituted heteroaryl,(j) aryl,(k) substituted aryl,(l) heteroaryl,(m) substituted heteroaryl,(n) C.sub.3 -C.sub.8 -cycloalkyl, and(o) substituted C.sub.3 -C.sub.8 -cycloalkyl,(2) C.sub.2 -C.sub.10 -alkyl substituted with one or more substituents selected from the group consisting of(a) halogen,(b) hydroxy,(c) C.sub.1 -C.sub.3 -alkoxy,(d) C.sub.1 -C.sub.3 -alkoxy-C.sub.1 -C.sub.3 -alkoxy,(e) oxo,(f) --N.sub.3,(g) --CHO,(h) O--SO.sub.2 -(substituted C.sub.1 -C.sub.6 -alkyl),(i) --NR.sup.13 R.sup.14 wherein R.sup.13 and R.sup.14 are selected from the group consisting of(i) hydrogen,(ii) C.sub.1 -C.sub.12 -alkyl,(iii) substituted C.sub.1 -C.sub.12 -alkyl,(iv) C.sub.1 -C.sub.12 -alkenyl,(v) substituted C.sub.1 -C.sub.12 -alkenyl,(vi) C.sub.1 -C.sub.12 -alkynyl,(vii) substituted C.sub.1 -C.sub.12 -alkynyl,(viii) aryl,(ix) C.sub.3 -C.sub.8 -cycloalkyl,(x) substituted C.sub.3 -C.sub.8 -cycloalkyl,(xi) substituted aryl,(xii) heterocycloalkyl,(xiii) substituted heterocycloalkyl,(xiv) C.sub.1 -C.sub.12 -alkyl substituted with aryl,(xv) C.sub.1 -C.sub.12 -alkyl substituted with substituted aryl,(xvi) C.sub.1 -C.sub.12 -alkyl substituted with heterocycloalkyl,(xvii) C.sub.1 -C.sub.12 -alkyl substituted with substituted heterocycloalkyl,(xviii) C.sub.1 -C.sub.12 -alkyl substituted with C.sub.3 -C.sub.8 -cycloalkyl,(xix) C.sub.1 -C.sub.12 -alkyl substituted with substituted C.sub.3 -C.sub.8 -cycloalkyl,(xx) heteroaryl,(xxi) substituted heteroaryl,(xxii) C.sub.1 -C.sub.12 -alkyl substituted with heteroaryl, and(xxiii) C.sub.1 -C.sub.12 -alkyl substituted with substituted heteroaryl, orR.sup.13 and R.sup.14 are taken together with the atom to which they are attached form a 3-10 membered heterocycloalkyl ring which may be substituted with one or more substituents independently selected from the group consisting of(i) halogen,(ii) hydroxy,(iii) C.sub.1 -C.sub.3 -alkoxy,(iv) C.sub.1 -C.sub.3 -alkoxy-C.sub.1 -C.sub.3 -alkoxy,(v) oxo,(vi) C.sub.1 -C.sub.3 -alkyl,(vii) halo-C.sub.1 -C.sub.3 -alkyl, and(vii) C.sub.1 -C.sub.3 -alkoxy-C.sub.1 -C.sub.3 -alkyl,(j) --CO.sub.2 R.sup.10 wherein R.sup.10 is as previously defined,(k) --C(O)NR.sup.11 R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined,(l) .dbd.N--O--R.sup.10 wherein R.sup.10 is as previously defined,(m) --CN,(n) S(O).sub.n R.sup.9 where n is 0, 1 or 2 and R.sup.9 is as previously defined,(o) O--S(O).sub.n R.sup.10 wherein n is 0, 1 or 2 and R.sup.10 is as previously defined,(p) --Si--(R.sup.2)(R.sup.3)(R.sup.4) wherein R.sup.2, R.sup.3 and R.sup.4 are as previously defined,(q) aryl,(r) substituted aryl,(s) heteroaryl,(t) substituted heteroaryl,(u) C.sub.3 -C.sub.8 -cycloalkyl,(v) substituted C.sub.3 -C.sub.8 -cycloalkyl,(w) C.sub.1 -C.sub.12 -alkyl substituted with heteroaryl,(x) heterocycloalkyl,(y) substituted heterocycloalkyl,(z) NHC(O)R.sup.10 where R.sup.10 is as previously defined,(aa) NHC(O)NR.sup.11 R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined,(bb) .dbd.N--NR.sup.13 R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined,(cc) .dbd.N--R.sup.9 wherein R.sup.9 is as previously defined,(dd) .dbd.N--NHC(O)R.sup.10 wherein R.sup.10 is as previously defined, and(ee) .dbd.N--NHC(O)NR.sup.11 R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined;(3) C.sub.3 -alkenyl substituted with a moiety selected from the group consisting of(a) halogen,(b) --CHO,(c) --CO.sub.2 R.sup.10 where R.sup.10 is as previously defined,(d) --C(O)--R.sup.9 where R.sup.9 is as previously defined,(e) --C(O)NR.sup.11 R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined,(f) --CN,(g) S(O).sub.n R.sup.9 where n is 0, 1 or 2 and R.sup.9 is as previously defined,(h) --Si--(R.sup.2)(R.sup.3)(R.sup.4) wherein R.sup.2, R.sup.3 and R.sup.4 are as previously defined,(i) aryl,(j) substituted aryl,(k) heteroaryl,(l) substituted heteroaryl,(m) C.sub.3 -C.sub.7 -cycloalkyl, and(n) C.sub.1 -C.sub.12 -alkyl substituted with heteroaryl,(4) C.sub.4 -C.sub.10 -alkenyl;(5) C.sub.4 -C.sub.10 -alkenyl substituted with one or more substituents selected from the group consisting of(a) halogen,(b) C.sub.1 -C.sub.3 -alkoxy,(c) oxo,(d) --CHO,(e) --CO.sub.2 R.sup.10 where R.sup.10 is as previously defined,(f) --C(O)NR.sup.11 R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined,(g) --NR.sup.13 R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined,(h) .dbd.N--O--R.sup.10 where R.sup.10 is as previously defined,(i) --CN,(j) O--S(O).sub.n R.sup.10 where n is 0, 1 or 2 and R.sup.10 is as previously defined,(k) aryl,(l) substituted aryl,(m) heteroaryl,(n) substituted heteroaryl,(o) C.sub.3 -C.sub.7 -cycloalkyl,(p) C.sub.1 -C.sub.12 -alkyl substituted with heteroaryl,(q) NHC(O)R.sup.10 where R.sup.10 is as previously defined,(r) NHC(O)NR.sup.11 R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined,(s) .dbd.N--NR.sup.13 R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined,(t) .dbd.N--R.sup.9 wherein R.sup.9 is as previously defined,(u) .dbd.N--NHC(O)R.sup.10 where R.sup.10 is as previously defined, and(v) .dbd.N--NHC(O)NR.sup.11 R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined;(6) C.sub.3 -C.sub.10 -alkynyl; and(7) C.sub.3 -C.sub.10 -alkynyl substituted with one or more substituents selected from the group consisting of(a) trialkylsilyl,(b) aryl,(c) substituted aryl,(d) heteroaryl, and(e) substituted heteroaryl.