Patent ID: 6034069
Filing Date: 2000-03-07
Classification: C07H

Abstract:
A compound selected from the group consisting of ##STR13## or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein R.sup.1 and R.sup.2, with the proviso that R.sup.1 and R.sup.2 are not both methyl, are independently selected from the group consisting of(1) hydrogen,(2) C.sub.1 -C.sub.6 -alkyl optionally substituted with a substituent selected from the group consisting of(a) halogen,(b) C.sub.3 -C.sub.6 -cycloalkyl,(c) aryl,(d) substituted aryl,(e) heteroaryl,(f) substituted heteroaryl,(g) --CHO,(h) --C(O)--C.sub.1 -C.sub.6 -alkyl, and(i) --C(O)--NR'R"", wherein R' and R"" are independently selected from the group consisting of hydrogen, C.sub.1 -C.sub.3 -alkyl, C.sub.1 -C.sub.3 -alkyl substituted with aryl, substituted aryl, heteroaryl, and substituted heteroaryl,(3) C.sub.2 -C.sub.6 -alkyl optionally substituted with a substituent selected from the group consisting of(a) C.sub.1 -C.sub.6 -alkoxy,(b) --NR'R"", wherein R' and R"" are as previously defined,(c) --NH--C(O)--C.sub.1 -C.sub.6 -alkyl,(d) --NH--C(O)--O--C.sub.1 -C.sub.6 -alkyl,(e) --O--C(O)--O--C.sub.1 -C.sub.6 -alkyl,(f) --O--C(O)--C.sub.1 -C.sub.6 -alkyl,(g) --CH(.dbd.N--O--C.sub.1 -C.sub.6 -alkyl),(h) --C(.dbd.N--O--C.sub.1 -C.sub.6 -alkyl)--C.sub.1 -C.sub.6 -alkyl,(i) --CH(.dbd.N--NH--C.sub.1 -C.sub.6 -alkyl), and(j) --C(.dbd.N--NH--C.sub.1 -C.sub.6 -alkyl)--C.sub.1 -C.sub.6 -alkyl,(4) C.sub.3 -C.sub.6 -alkenyl optionally substituted with a substituent selected from the group consisting of(a) halogen,(b) C.sub.3 -C.sub.6 -cycloalkyl,(c) aryl,(d) substituted aryl,(e) heteroaryl,(f) substituted heteroaryl,(g) --NH--C(O)--C.sub.1 -C.sub.6 -alkyl,(h) --NH--C(O)--O--C.sub.1 -C.sub.6 -alkyl,(i) --O--C(O)--O--C.sub.1 -C.sub.6 -alkyl,(j) --O--C(O)--C.sub.1 -C.sub.6 -alkyl,(k) --CHO,(l) --C(O)--C.sub.1 -C.sub.6 -alkyl,(m) --C(O)--NR'R"", wherein R' and R"" are as previously defined,(n) --CH(.dbd.N--O--C.sub.1 -C.sub.6 -alkyl),(o) --C(.dbd.N--O--C.sub.1 -C.sub.6 -alkyl)--C.sub.1 -C.sub.6 -alkyl,(p) --CH(.dbd.N--NH--C.sub.1 -C.sub.6 -alkyl),(q) --C(.dbd.N--NH--C.sub.1 -C.sub.6 -alkyl)--C.sub.1 -C.sub.6 -alkyl, and(r) --C(O)--O--C.sub.1 -C.sub.6 -alkyl,(5) C.sub.3 -C.sub.6 -alkynyl optionally substituted with a substituent selected from the group consisting of(a) halogen,(b) C.sub.3 -C.sub.6 -cycloalkyl,(c) aryl,(d) substituted aryl,(e) heteroaryl, and(f) substituted heteroaryl,(6) C.sub.3 -C.sub.6 -cycloalkyl,(7) --CHO,(8) --C(O)--C.sub.1 -C.sub.6 -alkyl,(9) --C(O)--NR'R"", wherein R' and R"" are as previously defined, and(10) --C(O)--O--C.sub.1 -C.sub.6 -alkyl, or R.sup.1 and R.sup.2 taken together may be --(CH.sub.2).sub.p --, wherein p is 3-to-7, which taken together with the nitrogen atom to which they are attached, thus form a heterocyclic ring containing one nitrogen atom and from 3 to 7 carbon atoms;R is selected from the group consisting of(1) methyl substituted with a substituent selected from the group consisting of(a) --CN,(b) --F,(c) --CO.sub.2 R.sup.3 wherein R.sup.3 is C.sub.1 -C.sub.3 -alkyl, aryl-substituted C.sub.1 -C.sub.3 -alkyl, or heteroaryl-substituted C.sub.1 -C.sub.3 -alkyl,(d) --S(O).sub.n --R.sup.3 wherein n is 0, 1, or 2, and R.sup.3 is as previously defined,(e) --NH--C(O)--R.sup.3 where R.sup.3 is as previously defined,(f) --NH--C(O)--NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are independently selected from the group consisting of(i) hydrogen,(ii) C.sub.1 -C.sub.3 -alkyl,(iii) C.sub.1 -C.sub.3 -alkyl substituted with aryl,(iv) C.sub.1 -C.sub.3 -alkyl substituted with substituted aryl,(v) C.sub.1 -C.sub.3 -alkyl substituted with heteroaryl, and(vi) C.sub.1 -C.sub.3 -alkyl substituted with and substituted heteroaryl,(g) aryl,(h) substituted aryl,(i) heteroaryl, and(j) substituted heteroaryl,(2) C.sub.2 -C.sub.10 -alkyl,(3) 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--SO2-(substituted C.sub.1 -C.sub.6 -alkyl),(i) --NR.sup.6 R.sup.7 wherein R.sup.6 and R.sup.7 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.6 and R.sup.7 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.3 wherein R.sup.3 is as previously defined,(k) --C(O)--NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are as previously defined,(l) .dbd.N--O--R.sup.3 wherein R.sup.3 is as previously defined,(m) --C.tbd.N,(n) --O--S(O).sub.n --R.sup.3 wherein n and R.sup.3 are as previously defined,(o) aryl,(p) substituted aryl,(q) heteroaryl,(r) substituted heteroaryl,(s) C.sub.3 -C.sub.8 -cycloalkyl,(t) substituted C.sub.3 -C.sub.8 -cycloalkyl,(u) C.sub.1 -C.sub.12 -alkyl substituted with heteroaryl,(v) heterocycloalkyl,(w) substituted heterocycloalkyl,(x) --NH--C(O)--R.sup.3 where R.sup.3 is as previously defined,(y) --NH--C(O)--NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are as previously defined,(z) .dbd.N--NR.sup.6 R.sup.7 wherein R.sup.6 and R.sup.7 are as previously defined,(aa) .dbd.N--R.sup.3 wherein R.sup.3 is as previously defined,(bb) .dbd.N--NH--C(O)--R.sup.4 wherein R.sup.4 is as previously defined, and(cc) .dbd.N--NH--C(O)--NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are as previously defined,(4) C.sub.3 -alkenyl substituted with a moiety selected from the group consisting of(a) halogen,(b) --CHO,(c) --CO.sub.2 R.sup.3 where R.sup.3 is as previously defined,(d) --C(O)--R.sup.4 where R.sup.4 is as previously defined,(e) --C(O)--NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are as previously defined,(f) --C.tbd.N,(g) aryl,(h) substituted aryl,(i) heteroaryl,(j) substituted heteroaryl,(k) C.sub.3 -C.sub.7 -cycloalkyl, and(l) C.sub.1 -C.sub.12 -alkyl substituted with heteroaryl,(5) C.sub.4 -C.sub.10 -alkenyl,(6) 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 -atkoxy,(c) oxo,(d) --CHO,(e) --CO.sub.2 R.sup.3 where R.sup.3 is as previously defined,(f) --C(O)--NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are as previously defined,(g) --NR.sup.6 R.sup.7 wherein R.sup.6 and R.sup.7 are as previously defined,(h) .dbd.N--O--R.sup.3 wherein R.sup.3 is as previously defined,(i) --C.tbd.N,(j) --O--S(O).sub.n --R.sup.3 wherein n is 0, 1, or 2 and R.sup.3 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) --NH--C(O)--R.sup.3 where R.sup.3 is as previously defined,(r) --NH--C(O)--NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are as previously defined,(s) .dbd.N--NR.sup.6 R.sup.7 wherein R.sup.6 and R.sup.7 are as previously defined,(t) .dbd.N--R.sup.3 wherein R.sup.3 is as previously defined,(u) .dbd.N--NH--C(O)--R.sup.3 where R.sup.3 is as previously defined, and(v) .dbd.N--NH--C(O)--NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are as previously defined,(7) C.sub.3 -C.sub.10 -alkynyl, and(8) 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,with the proviso that when R is allyl and R.sup.1 is methyl, R.sup.2 is not H;R.sup.p is hydrogen or a hydroxy protecting group;R.sup.w is selected from the group consisting of(1) hydrogen,(2) C.sub.1 -C.sub.6 -alkyl, optionally substituted with one or more substituents selected from the group consisting of(a) aryl,(b) substituted aryl,(c) heteroaryl,(d) substituted heteroaryl,(3) a group selected from option (2) as previously defined further substituted with --CH.sub.2 --M--R.sup.8, wherein M is selected from the group consisting of(i) --O--,(ii) --NH--,(ii) --N(CH.sub.3)--,(iv) --S(O).sub.n --, wherein n is as described previously,(v) --NH--C(O)--, and(vi) --C(O)--NH--, andR.sup.8 is selected from the group consisting of(i) --(CH.sub.2).sub.n -aryl, wherein n is as described previously,(ii) --(CH.sub.2).sub.n -substituted aryl, wherein n is as described previously,(iii) --(CH.sub.2).sub.n -heteroaryl, wherein n is as described previously,(iv) --(CH.sub.2).sub.n -substituted heteroaryl, wherein n is as described previously, and(v) --(CH.sub.2).sub.n -heterocycloalkyl, wherein n is as described previously; andW is absent or is selected from the group consisting of --O--, --NH-- and --N(CH.sub.3)--.