Claims
- 1. A compound represented by structural formula (II): ##STR3539## where R.sup.1 is selected from the group ##STR3540## R and R' are independently selected from the group hydrogen,
- halo(F, a, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkoxy,
- hydroxy,
- hydroxy-C.sub.1 -C.sub.6 alkyl,
- C.sub.16 -C.sub.6 alkylcarbonyl, and
- W' is selected from one to three substituents selected from the group
- hydrogen,
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- R.sup.8 and
- V;
- R.sup.7 is selected from the group,
- hydrogen, benzyl,
- C.sub.1 -C.sub.4 alkyl and halo (F, CL, Br, L)C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.8 alkyl,
- C.sub.2 -C.sub.8 alkenyl,
- C.sub.2 -C.sub.8 alkenyl,
- C.sub.3 -C.sub.2 cycloalkyl-C.sub.1 -C.sub.3 aklyl,
- C.sub.3 -C.sub.12 cycloalkyl,
- C.sub.1 -C.sub.4 alkyl-Z--C.sub.1 -C.sub.4 alkyl, where Z is S or O,
- C.sub.2 -C.sub.4 alkyl-NR--C.sub.2 -C.sub.4 alkyl,
- C.sub.2 -C.sub.4 alkyl-C.sub.6 -C.sub.12 aryl,
- C.sub.2 -C.sub.4 alkyl-C.sub.6 -C.sub.12 cycloalkyl,
- C.sub.2 -C.sub.8 alkenyl,
- C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl,
- C.sub.6 -C.sub.12 aryl-C.sub.2 -C.sub.4 alkynyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
- where any aryl, alkyl, cycloalkyl or alkenyl moiety is optionally substituted with halo(F, Cl, Br, I), or --OR.sup.9 ;
- R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a heterocyclic 5-, 6-, or 7-member ring containing 0, 1, or 2 additional heteroatoms selected from N, S, and O, optionally the heterocyclic ring is substituted with one or two groups selected from
- oxo(.dbd.O),
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl,
- C.sub.2 -C.sub.8 alkenyl,
- C.sub.3 -C.sub.12 cycloalkyl-C.sub.1 -C.sub.4 alkyl,
- C.sub.3 -C.sub.12 cycloalkyl
- C.sub.1 -C.sub.4 alkyl-Z--C.sub.1 -C.sub.4 aklyl, where Z is S or O,
- C.sub.2 -C.sub.4 alkyl-NR--C.sub.2 -C.sub.4 alkyl,
- C.sub.2 -C.sub.4 alkyl-C.sub.6 -C.sub.12 aryl,
- C.sub.2 -C.sub.4 alkyl-C.sub.6 -C.sub.12 cycloalkyl,
- C.sub.2 -C.sub.8 alkenyl,
- C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.4 alkyl,
- C.sub.6 -C.sub.12 aryl-C.sub.2 -C.sub.4 alkynyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-C.sub.1 -C.sub.3 alkyl,
- where any aryl moiety is optionally substituted with halo(F, Cl, Br, I), --OR.sup.9 and V, and where any alkyl, cycloaLkyl or alkenyl group is optionally substituted with one to three groups selected from the group
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- NH--C(.dbd.NH)--NH.sub.2,
- C(.dbd.O)NHOH,
- C(.dbd.O)OR.sup.9,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28 and
- V;
- V is selected from the group
- COR.sup.10,
- SO.sub.3 R.sup.13,
- NHSO.sub.2 CF.sub.3,
- PO(OR.sup.13).sub.2,
- SO.sub.2 NHR.sup.10,
- CONHOR.sup.13,
- C(OH)R.sup.10 PO(OR.sup.13).sub.2,
- CN,
- SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S, and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- CN,
- C.sub.1 -C.sub.4 alky,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl)
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl),
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- CONHSO.sub.2 R.sup.15,
- SO.sub.2 NHCOR.sup.15,
- CONHSO.sub.2 R.sup.13,
- CH.sub.2 CONHSO.sub.2 R.sup.15,
- NHCONHSO.sub.2 R.sup.15,
- NHSO.sub.2 NHCOR.sup.15,
- CONHNHSO.sub.2 CF.sub.3,
- CON(OH)R.sup.13,
- CONHCOCF.sub.3,
- CONHSO.sub.2 R.sup.10,
- CONHSO.sub.2 R.sup.11,
- CONHSO.sub.2 R.sup.13, ##STR3541## R.sup.9 is selected from the group hydrogen,
- methyl,
- ethyl,
- isopropyl
- phenyl, and
- benzy
- R.sup.10 is selected from the group
- hydroxy,
- C.sub.1 -C.sub.8 -alkoxy,
- C.sub.3 -C.sub.12 -alkenoxy,
- C.sub.6 -C.sub.12 -aryloxy,
- C.sub.1 -C.sub.6 alkyl-C.sub.6 -C.sub.12 -aryloxy,
- di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
- alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
- acetylaminoethoxy,
- nicotinoylaminoethoxy, and
- succinamidoethoxy,
- C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino,
- hydroxy-C.sub.2 -C.sub.8 -alkoxy,
- dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
- NR.sup.11 R.sup.12 ;
- R.sup.11 and R.sup.12 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino, and
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from the group
- nitro,
- halo(F, a, Br, I), and
- C.sub.1 -C.sub.4 -alkoxy;
- R.sup.13 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)-C.sub.1 -C.sub.6 alkyl,
- phenyl,
- benzyl, and
- CH.sub.2 --O--COCH.sub.3 ;
- R.sup.15 is selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl, where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alky,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- C.sub.3 -C.sub.7 -cycloalkyl,
- C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl as defined above,
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- C.sub.1 -C.sub.4 alkylthio,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- CO.sub.2 H,
- CO.sub.2 -C.sub.1 -C.sub.4 -alkyl,
- NH.sub.2,
- N�(C.sub.1 -C.sub.4)-alkyl!.sub.2,
- NH�(C.sub.1 -C.sub.4)-alkyl!,
- PO.sub.3 H,
- PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
- C.sub.1 -C.sub.4 -perfluoroalkl;
- R.sup.16 is selected from the group
- CN,
- NO.sub.2,
- COOR.sup.13,
- C.sub.1 -C.sub.6 -perfluoroalkyl, and
- CF.sub.3 ;
- R.sup.19 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 -alkyl
- C.sub.2 -C.sub.6 -alkenyl,
- C.sub.1 -C.sub.6 -alkoxy,
- C.sub.2 -C.sub.6 -alkoxyalkyl,
- CH.sub.2 --O--COCH.sub.3, and
- benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from the group
- NO.sub.2,
- NH.sub.2,
- OH, and
- OCH.sub.3 ;
- X is selected from the group
- NR.sup.24 --C(.dbd.O)--R.sup.25,
- NR.sup.24 --C(.dbd.O)--R.sup.8,
- NR.sup.24 --C(.dbd.O)--NR.sup.7 'R.sup.8,
- NR.sup.24 --C(.dbd.O)O--R.sup.8,
- NR.sup.24 --C(.dbd.O)S--R.sup.8,
- (CH.sub.2).sub.1-4 --NR.sup.24 --C(.dbd.O)-R.sup.25,
- NR.sup.24 --CH(OH)--R.sup.25,
- NR.sup.24 --CH.sub.2 --R.sup.25,
- NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0,1, or 2,
- CHR.sup.24 --O--R.sup.25,
- CHR.sup.24 --CH.sub.2 R.sup.25,
- CHR.sup.24 --R.sup.25,
- CR.sup.24 .dbd.CHR.sup.25 (E or Z),
- (CH.sub.2).sub.1-4 --C(.dbd.O)--R.sup.25,
- C.sub.6 -C.sub.10 aryl-R.sup.25,
- heterocyle-R.sup.25,
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
- C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25,
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- R.sup.24 is selected from the group
- hydrogen,
- benzyl,
- halo(F, a, Br, I)benzyl,
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.25 is selected from R.sup.25, ##STR3542## R.sup.25 ' is selected from the group SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkylamine,
- C.sub.2 -C.sub.6 alkenylamine, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- where any alkyl or alkenyl moiety is optionally substituted with one to three
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26, and
- NR.sup.27 R.sup.28,
- where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
- R.sup.26 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkanoyl;
- R.sup.27 and R.sup.28 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- phenyl,
- napthyl,
- benzyl,
- CH.sub.2 napthyl (.alpha. or .beta.)
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 cycloalkanoyl,
- C.sub.6 -C.sub.10 aroyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkylsulfonyl,
- C.sub.6 -C.sub.10 arylsulfonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
- cinnamoyl,
- heterocyclecarbonyl,
- C.sub.1 -C.sub.6 alkoxycarbonyl,
- C.sub.6 -C.sub.10 aryloxycarbonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
- pyroglutamyl;
- R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3543## and a cyclic imide represented by ##STR3544## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0, 1, or 2, and NR.sup.28 ;
- J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
- R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl; and
- pharmaceutically acceptable salts thereof.
- 2. The compound of claim 1 represented by structural formula (IIa): ##STR3545## where R and R' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkoxy;
- R.sup.4 and R.sup.4 ' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- R.sup.7 is hydrogen;
- R.sup.7 ' is selected from the group
- hydrogen,
- benzyl,
- C.sub.1 -C.sub.4 alkyl, and halo (F, Cl, B, I)C.sub.1 -C.sub.4 alkyl,
- C.sub.3 -C.sub.8 cycloalkyl,
- C.sub.3 -C.sub.8 cycloalkyl-C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl
- C.sub.1 -C.sub.4 alkyl-Z--C.sub.1 -C.sub.4 alkyl, where Z is S or O,
- C.sub.2 -C.sub.4 alkyl-NR--C.sub.2 -C.sub.4 alkyl,
- C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-yl-C.sub.1 -C.sub.3 alkyl, and
- where any aryl moiety is optionally substituted with --OR.sup.9, and where any alkyl group is optionally substituted with one or two groups selected from the group
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- R.sup.9 is selected from the group
- hydrogen,
- methyl,
- ethyl,
- isopropyl,
- t-butyl,
- phenyl, and
- benzyl;
- V is selected from the group
- COR.sup.10, and ##STR3546## R.sup.10 is selected from the group hydroxy, and
- C.sub.1 -C.sub.8 -alkoxy;
- R.sup.19 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 -alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 -alkyl;
- X is selected from the group
- NR.sup.24 --C(.dbd.O)--R.sup.25,
- NR.sup.24 --C(.dbd.O)--R.sup.8,
- NR.sup.24 --C(.dbd.O)--NR.sup.7 'R.sup.8,
- NR.sup.24 --C(.dbd.O)O--R.sup.8,
- NR.sup.24 --C(.dbd.O)S--R.sup.8,
- NR.sup.24 --CH(OH)--R.sup.25,
- NR.sup.24 --CH.sub.2 --R.sup.2,
- NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0, 1, or 2,
- CHR.sup.24 --CH.sub.2 R.sup.25,
- CHR.sup.24 --R.sup.25,
- CR.sup.24 .dbd.CHR.sup.25 (E or Z),
- C.sub.6 -C.sub.10 aryl-R.sup.25,
- heterocycle-R.sup.25,
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
- C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25, where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- R.sup.24 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.25 is selected from R25', ##STR3547## R.sup.25 ' is selected from the group SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkylamine,
- C.sub.2 -C.sub.6 alkenylamine, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- where any alkyl or alkenyl moiety is optionally substituted with
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26, and
- NR.sup.27 R.sup.28,
- where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
- R.sup.26 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkanoyl;
- R.sup.27 and R.sup.28 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- phenyl,
- napthyl,
- benzyl,
- CH.sub.2 napthyl (.alpha. or .beta.)
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 cycloalkanoyl,
- C.sub.6 -C.sub.10 aroyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkylsulfonyl,
- C.sub.6 -C.sub.10 arylsulfonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
- cinnamoyl,
- heterocyclecarbonyl,
- C.sub.1 -C.sub.6 alkoxycarbonyl,
- C.sub.6 -C.sub.10 aryloxycarbonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
- pyroglutamyl;
- R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3548## G is selected from --CH.sub.2 --, O, S(O).sub.u where u, is 0, 1, or 2, and NR.sup.28, and pharmaceutically acceptable salts thereof.
- 3. The compound of claim 2 represented by structural formula (IIb): ##STR3549## where R and R' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkoxy;
- R.sup.4 and R.sup.4 ' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.7 is hydrogen;
- R.sup.7 ' is selected from the group
- hydrogen,
- benzyl,
- C.sub.1 -C.sub.4 alkyl, and halo (F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl,
- C.sub.1 -C.sub.4 alkyl-Z--C.sub.1 -C.sub.4 alklyl, where Z is S or O,
- C.sub.2 -C.sub.4 alkyl-NR--C.sub.2 -C.sub.4 alkyl,
- C.sub.2 -C.sub.8 alkenyl,
- C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
- where any aryl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from the group
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- NH--C(.dbd.NH)--NH.sub.2,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V is selected from the group
- COR.sup.10, and ##STR3550## R.sup.9 is selected from the group hydrogen,
- methyl,
- ethyl,
- isopropyl,
- t-butyl,
- phenyl, and
- benzyl;
- R.sup.10 is selected from the group
- hydroxy,
- C.sub.3 -C.sub.8 -cycloalkoxy, and
- C.sub.1 -C.sub.8 -alkoxy;
- R.sup.19 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 -alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 -alkyl;
- X is selected from the group
- NR.sup.24 --C(.dbd.O)--R.sup.25,
- NR.sup.24 --C(.dbd.O)--NR.sup.7 'R.sup.8,
- NR.sup.24 --C(.dbd.O)O--R.sup.8
- NR.sup.24 --CH(OH)--R.sup.25,
- NR.sup.24 --CH.sub.2 --R.sup.25,
- NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0, 1, or 2,
- CHR.sup.24 --CH.sub.2 R.sup.25,
- CHR.sup.24 --R.sup.25,
- CR.sup.24 .dbd.CHR.sup.25 (E or Z),
- C.sub.6 -C.sub.10 aryl-R.sup.25,
- heterocycle-R.sup.25,
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
- C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25, where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected fromO, N, and S;
- R.sup.24 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 aLkyl;
- R.sup.25 is selected from the group R.sup.25 ', ##STR3551## R.sup.25 ' is C.sub.1 -C.sub.6 alkyl, substituted with one or two groups selected from the group
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26, and
- NR.sup.27 R.sup.28,
- where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
- R.sup.25 " is selected from the group
- C.sub.1 -C.sub.6 alkyl,
- halo(F,Cl,Br, I)C.sub.1 -C.sub.6 alkyl,
- C.sub.6 -C.sub.12 alkyl,
- C.sub.6 -C.sub.12 arylC.sub.1 -C.sub.3 alkyl,
- where any alkyl or aryl group is optionally substituted with a group selected SR.sup.26,
- SSR.sup.26,
- COR.sup.10,
- OR.sup.26, and
- NOR.sup.26 ;
- R.sup.26 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkanoyl;
- R.sup.27 and R.sup.28 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- phenyl,
- napthyl,
- benzyl,
- CH.sub.2 napthyl (.alpha. or .beta.)
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 cycloalkanoyl,
- C.sub.6 -C.sub.10 aroyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkylsulfonyl,
- C.sub.6 -C.sub.10 arylsulfonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
- cinnamoyl,
- heterocyclecarbonyl,
- C.sub.1 -C.sub.6 alkoxycarbonyl,
- C.sub.6 -C.sub.10 aryloxycarbonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
- pyroglutamyl;
- R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3552## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0,1,or 2, and NR.sup.28, and
- pharmaceutically acceptable salts thereof.
- 4. The compound of claim 1 represented by structural formula (IIc): ##STR3553## where R and R' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkoxy,
- hydroxy,
- hydroxy-C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkylcarbonyl, and
- C.sub.1 -C.sub.6 alkyloxycarbonyl;
- R.sup.4 and R.sup.4 ' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- phenyl, and
- benzyl;
- R.sup.7 is selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- W is selected from the group
- C(.dbd.O)--NR.sup.7 'R.sup.8,
- CH.sub.2 --C(.dbd.O)--NR.sup.7 'R.sup.8,
- C(.dbd.O)--O--R.sup.8,
- CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--CHR.sup.7 R.sup.8,
- CR.sup.8 '.dbd.CR.sup.7 R.sup.8 (E or Z),
- C(.dbd.O)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--NR.sup.7 'R.sup.8,
- CHR.sup.8 '--O--R.sup.8,
- CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0,1, or 2,
- CR.sup.8 '.dbd.N--R.sup.8,
- CHR.sup.8 '--R.sup.8,
- W',
- C.sub.1 -C.sub.3 alkyl-W',
- C.sub.6 -C.sub.12 aryl-W',
- C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl-W',
- heterocycle-W',
- heterocycle-C.sub.1 -C.sub.3 alkyl-W',
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-W', and
- C.sub.1 -C.sub.2 alkyl-heterocycle-W',
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- W' is selected from one to three substituents selected from the group
- hydrogen,
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- R.sup.8 and
- V;
- R.sup.7 'is selected from the group
- hydrogen,
- benzyl,
- C.sub.1 -C.sub.4 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl,
- C.sub.2 -C.sub.8 alkenyl,
- phenyl-C.sub.1 -C.sub.3 alkyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
- where any phenyl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- NH--C(.dbd.NH)--NH.sub.2,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- V is selected from the group
- COR.sup.10,
- SO.sub.3 R.sup.13,
- NHSO.sub.2 CF.sub.3,
- PO(OR.sup.13).sub.2,
- SO.sub.2 NHR.sup.10,
- CONHOR.sup.13,
- C(OH)R.sup.10 PO(OR.sup.13).sub.2,
- CN,
- SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- CONHSO.sub.2 R.sup.15,
- SO.sub.2 NHCOR.sup.15,
- CONHSO.sub.2 R.sup.13,
- CH.sub.2 CONHSO.sub.2 R.sup.15,
- NHCONHSO.sub.2 R.sup.15,
- NHSO.sub.2 NHCOR.sup.15,
- CONHNHSO.sub.2 CF.sup.3,
- CON(OH)R.sup.13,
- CONHCOCF.sub.3,
- CONHSO.sub.2 R.sup.10,
- CONHSO.sub.2 R.sup.11,
- CONHSO.sub.2 R.sup.13, ##STR3554## R.sup.9 is selected from the group hydrogen,
- methyl,
- ethyl,
- isopropyl,
- t-butyl,
- phenyl, and
- benzyl;
- R.sup.10 is selected from the group
- hydroxy,
- C.sub.1 -C.sub.8 -alkoxy,
- C.sub.3 -C.sub.12 -alkenoxy,
- C.sub.6 -C.sub.12 -aryloxy,
- C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 -aryloxy,
- di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
- alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
- acetylaminoethoxy,
- nicotinoylaminoethoxy, and
- succinamidoethoxy,
- C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino,
- hydroxy-C.sub.2 -C.sub.8 -alkoxy,
- dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
- NR.sup.11 R.sup.12 ;
- R.sup.11 and R.sup.12 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino, and
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
- nitro,
- halo(F, Cl, Br, I), and
- C.sub.1 -C4-alkoxy;
- R.sup.13 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)-C.sub.1 -C.sub.6 alkyl,
- phenyl,
- benzyl, and
- CH.sub.2 --O--COCH.sub.3 ;
- R.sup.15 is selected from the group
- C.sub.6 -C.sub.4 aryl,
- heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- C.sub.3 -C.sub.7 -cycloalkyl,
- C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl as defined above,
- OH,
- SH,
- C.sub.1 -C.sub.4 -alkyl,
- C.sub.1 -C.sub.4 -alkoxy,
- C.sub.1 -C.sub.4 -alkylthio,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- CO.sub.2 H,
- CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl,
- NH.sub.2,
- N�(C.sub.1 -C.sub.4)-alkyl!.sub.2,
- NH�(C.sub.1 -C.sub.4)-alkyl!,
- PO.sub.3 H,
- PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
- (C.sub.1 -C.sub.4)-perfluoroalkyl;
- R.sup.16 is selected from the group
- CN,
- N.sub.2,
- COOR.sup.13,
- C.sub.1 -C.sub.6 -perfluoroalkyl, and
- CF.sub.3 ;
- R.sup.19 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkoxy,
- C.sub.2 -C.sub.6 alkoxyalkyl,
- CH.sub.2 --O--COCH.sub.3, and
- benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from the group
- NO.sub.2,
- NH.sub.2,
- OH, and
- OCH.sub.3 ;
- R.sup.24 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.25 is selected from R.sup.25 ', ##STR3555## R.sup.25 ' is selected from the group SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkylamine,
- C.sub.2 -C.sub.6 alkenylamine, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- where any alkyl or alkenyl moiety is optionally substituted with one to three
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26.sub.1
- NOR.sup.26, and
- NR.sup.27 R.sup.28,
- where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
- R.sup.26 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkanoyl;
- R.sup.27 and R.sup.28 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- phenyl,
- napthyl,
- benzyl,
- CH.sub.2 napthyl (.alpha. or .beta.)
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 cycloalkanoyl.
- C.sub.6 -C.sub.10 aroyl,
- C.sub.6 -C.sub.10 aryl-C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkylsulfonyl,
- C.sub.6 -C.sub.10 arylsulfonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
- cinnamoyl,
- heterocyclecarbonyl,
- C.sub.1 -C.sub.6 alkoxycarbonyl,
- C.sub.6 -C.sub.10 aryloxycarbonyl,
- C.sub.6 -C.sub.10 arylC.sub.10 -C.sub.6 alkoxycarbonyl, and
- pyroglutamyl;
- R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3556## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0,1,or 2, and NR.sup.28, and
- pharmaceutically acceptable salts thereof.
- 5. The compound of claim 3 represented by structural formula (IId); ##STR3557## where R and R' are hydrogen or chloro;
- R.sup.4, R.sup.4 ', R.sup.7, and R.sup.8 are hydrogen;
- W is selected from the group
- C(.dbd.O)--NR.sup.7 'R.sup.8,
- CH.sub.2 --C(.dbd.O)--NR.sup.7 'R.sup.8,
- C(.dbd.O)--O--R.sup.8,
- CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--CHR.sup.7 R.sup.8,
- CR.sup.8 '.dbd.CR.sup.7 R.sup.8 (E or Z),
- C(.dbd.O)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--NR.sup.7 'R.sup.8,
- CHR.sup.8 '--O--R.sup.8,
- CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0, 1, or 2,
- CR.sup.8 '.dbd.N--R.sup.8,
- CHR.sup.8 '---R.sup.8,
- W',
- C.sub.1 -C.sub.3 alkyl-W'
- C.sub.6 -C.sub.12 aryl-W',
- heterocycle-W',
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-W', and
- C.sub.1 -C.sub.2 alkyl-heterocycle-W', where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- W' is selected from one to three substituents selected from the group
- hydrogen,
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- R.sup.8 and
- V;
- R.sup.7 ' is selected from the group
- hydrogen,
- benzyl,
- C.sub.1 -C.sub.4 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl,
- C.sub.2 -C.sub.8 alkenyl,
- phenyl-C.sub.1 -C.sub.3 alkyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
- where any phenyl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.O)NHOH,
- NHR.sup.9, and
- V;
- V is selected from the group
- halo(F, Cl, Br, I),
- CN,
- NO.sub.2,
- COR.sup.10,
- SO.sub.3 R.sup.13,
- NHSO.sub.2 CF.sub.3, and ##STR3558## R.sup.9 is selected from the group hydrogen,
- methyl,
- ethyl,
- isopropyl,
- t-butyl,
- phenyl, and
- benzyl;
- R.sup.10 is selected from the group
- hydroxy,
- C.sub.1 -C.sub.8 -alkoxy,
- C.sub.3 -C.sub.12 -alkenoxy,
- C.sub.6 -C.sub.12 -aryloxy,
- C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 -aryloxy,
- di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
- alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
- acetylaminoethoxy,
- nicotinoylaminoethoxy, and
- succinamidoethoxy,
- C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino,
- hydroxy-C.sub.2 -C.sub.8 -alkoxy,
- dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
- NR.sup.11 R.sup.12 ;
- R.sup.1 land R.sup.12 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino, and
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
- nitro,
- halo(F, Cl, Br, I), and
- C.sub.1 -C.sub.4 -alkoxy;
- R.sup.13 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
- phenyl,
- benzyl, and
- CH.sub.2 --O--COCH.sub.3 ;
- R.sup.19 is selected from the group
- hydrogen, and
- (C.sub.1 -C.sub.6)-alkyl;
- R.sup.24 is selected from the group
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.25 ' is C.sub.1 -C.sub.6 alkyl, substituted with a group selected from
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26, and
- NOR.sup.26,
- R.sup.26 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkanoyl;
- R.sup.27 and R.sup.28 are selected from
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- haloC.sub.1 -C.sub.6 alkyl,
- or together with the nitrogen to which they are bonded may form morpholino; and
- pharmaceutically acceptable salts thereof.
- 6. The compound of claim 3 represented by structural formula (IIe): ##STR3559## where R and R' are each independently selected from the group
- hydrogen,
- halo,
- C.sub.1 -C.sub.6 alkyl,
- halo-C.sub.1 -C.sub.6 -alkyl, and
- C.sub.1 -C.sub.6 alkoxy;
- R.sup.4 and R.sup.4 ' are independently selected from the group
- hydrogen,
- halo,
- C.sub.1 -C.sub.6 alkyl, and
- halo C.sub.1 -C.sub.6 alkyl;
- R.sup.7 ' and R.sup.24 are selected from the gro
- hydrogen,
- benzyl,
- C.sub.1 -C.sub.4 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.6 alkyl, and
- halo C.sub.1 -C.sub.6 alkyl;
- R.sup.10 is selected from the group
- hydroxy,
- amino,
- C.sub.1 -C.sub.6 alkylamino,
- di(C.sub.1 -C.sub.6) alkylamino,
- C.sub.1 -C.sub.6 alkoxy,
- C.sub.3 -C.sub.8 cycloalkoxy,
- C.sub.6 -C.sub.12 aryloxy,
- C.sub.1 -C.sub.6 alkyl C.sub.6 -C.sub.12 aryloxy,
- C.sub.2 -C.sub.6 acylamino C.sub.1 -C.sub.6 alkoxy,
- C.sub.1 -C.sub.6 alkanoyloxy C.sub.1 -C.sub.6 alkoxy,
- hydroxy C.sub.2 -C.sub.6 alkoxy, and
- dihydroxy C.sub.3 -C.sub.6 alkoxy;
- R.sup.27 and R.sup.28 are independently selected from the group
- hydrogen, and
- C.sub.1 -C.sub.6 alkyl;
- R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3560## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0, 1, or 2, and NR.sup.28 ; and
- pharmaceutically acceptable salts thereof.
- 7. A compound represented by structural formula (II): ##STR3561## where R and R' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkoxy,
- hydroxy,
- hydroxy-C.sub.1 -C.sub.6 aLkyl,
- C.sub.1 -C.sub.6 alkylcarbonyl, and
- C.sub.1 -C.sub.6 alkyloxycarbonyl;
- R.sup.1 and R.sup.2 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)-C.sub.1 -C.sub.6 alkyl, and ##STR3562## R.sup.1 and R.sup.2 taken together may form a covalent bond or fused benzene substituted with R and R';
- R.sup.4 and R.sup.4 ' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- phenyl, and
- benzyl;
- R.sup.7 is selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 aLkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- W is selected from the group
- C(.dbd.O)--NR.sup.7 'R.sup.8,
- CH.sub.2 --C(.dbd.O)--NR.sup.7 'R.sup.8,
- C(.dbd.O)--R.sup.8,
- CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--CHR.sup.7 R.sup.8,
- CR.sup.8 '.dbd.CR.sup.7 R.sup.8 (E or Z),
- C(.dbd.O)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--NR.sup.7 'R.sup.8,
- CHR.sup.8 '--O--R.sup.8,
- CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0, 1, or 2,
- CR.sup.8 '.dbd.N--R.sup.8,
- CHR.sup.8 '--R.sup.8,
- W',
- C.sub.1 -C.sub.3 alkyl-W',
- C.sub.6 -C.sub.12 aryl-W',
- C.sub.6 -C.sub.12 arYl-C.sub.1 -C.sub.3 alkyl-W',
- heterocycde-W',
- heterocycl-C.sub.1 -C.sub.3 alkyl-W',
- C.sub.1 -C.sub.12 alkyl-C.sub.6 -C.sub.10 aryl-W', and
- C.sub.1 -C.sub.2 alkyl-heterocyde-W',
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- W' is selected from one to three substituents selected from the group
- hydrogen,
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- R.sup.8, and
- V;
- R.sup.7 ' is selected from the group
- hydrogen,
- benzyl,
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a pyrrolidinyl or piperidyl ring optionally substituted with one or two groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl,
- C.sub.1 -C.sub.4 alkyl-Z--C.sub.1 -C.sub.4 alkyl, where Z is S or O,
- C.sub.2 -C.sub.4 alkyl-NR--C.sub.2 -C.sub.4 alkyl,
- C.sub.2 -C.sub.8 alkenyl,
- C.sub.6 -C.sub.12 arylC.sub.1 -C.sub.3 alkyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol4-yl-C.sub.1 -C.sub.3 alkyl,
- where any aryl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- NH--C(.dbd.NH)--NH.sub.2,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- V is selected from the group
- COR.sup.10,
- SO.sub.3 R.sup.13,
- NHSO.sub.2 CF.sub.3,
- PO(OR.sup.13).sub.2,
- SO.sub.2 NHR.sup.10,
- CONHOR.sup.13,
- C(OH)R.sup.10 PO(OR.sup.13).sub.2,
- halo(F, Cl, Br, I),
- NO.sub.2,
- CN,
- SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO-(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- CONHSO.sub.2 R.sup.15,
- SO.sub.2 NHCOR.sup.15,
- CONHSO.sub.2 R.sup.13,
- CH.sub.2 CONHSO.sub.2 R.sup.15,
- NHCONHSO.sub.2 R.sup.15,
- NHSO.sub.2 NHCOR.sup.15,
- CONHNHSO.sub.2 CF.sub.3,
- CON(OH)R.sup.13,
- CONHCOCF.sub.3,
- CONHS.sub.2 R.sup.10,
- CONHSO.sub.2 R.sup.11,
- CONHSO.sub.2 R.sup.13, ##STR3563## R.sup.9 is selected from the group hydrogen,
- methyl,
- ethyl,
- isopropyl,
- t-butyl,
- phenyl, and
- benzyl;
- R.sup.10 is selected from the group
- hydroxy,
- C.sub.1 -C.sub.8 -alkoxy,
- C.sub.3 -C.sub.12 -alkenoxy,
- C.sub.6 -C.sub.12 -aryloxy,
- C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 aryloxy,
- di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
- alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
- acetylaminoethoxy,
- nicotinoylaminoethoxy, and
- succinamidoethoxy, and
- C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino,
- hydroxy-C.sub.2 -C.sub.8 -alkoxy,
- dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
- NR.sup.11 R.sup.12 ;
- R.sup.11 and R.sup.12 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alanoyl,
- C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino, and
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
- nitro,
- halo(F, Cl, Br, I), and
- C.sub.1 -C.sub.4 -alkoxy;
- R.sup.13 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
- phenyl,
- benzyl, and
- CH.sub.2 --O--COCH.sub.3 ;
- R.sup.15 is selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 aLkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- C.sub.3 -C.sub.7 -cycloalkyl,
- C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl as defined above,
- OH,
- SH,
- C.sub.1 -C.sub.4 -alkyl,
- C.sub.1 -C.sub.4 -alkoxy,
- C.sub.1 -C.sub.4 -alkylthio,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- CO.sub.2 H,
- CO.sub.2 -(C.sub.1 -C.sub.4)-alkyl,
- NH.sub.2,
- N�(C.sub.1 -C.sub.4)-alkyl!.sub.2,
- NH�(C.sub.1 -C.sub.4)-alkyl!,
- PO.sub.3 H,
- PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
- (C.sub.1 -C.sub.4)-perfluoroalkyl;
- R.sup.16 is selected from the group
- CN,
- NO.sub.2,
- COOR.sup.13,
- C.sub.1 -C.sub.6 -perfluoroalkyl, and
- CF.sub.3 ;
- R.sup.19 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkoxy,
- C.sub.2 -C.sub.6 alkoxyalkyl,
- CH.sub.2 --O--COCH.sub.3, or
- benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from
- NO.sub.2,
- NH.sub.2,
- OH, or
- OCH.sub.3 ;
- X is selected from the group
- NR.sup.24 --C(.dbd.O)--R.sup.25,
- NR.sup.24 --C(.dbd.O)--R.sup.8,
- NR.sup.24 --C(.dbd.O)NH--R.sup.8,
- NR.sup.24 --C(.dbd.O)O--R.sup.8,
- NR.sup.24 --C(.dbd.O)S--R.sup.8,
- NR.sup.24 --CH(OH)--R.sup.25,
- NR.sup.24 --CH.sub.2 --R.sup.25,
- NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0, 1, or 2,
- CHR.sup.24 --CH.sub.2 R.sup.25,
- CHR.sup.24 --R.sup.25,
- CR.sup.24 .dbd.CHR.sup.25 (E or Z),
- C.sub.6 -C.sub.10 aryl-R.sup.25,
- heterocycle-R.sup.25,
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
- C.sub.1 -C.sub.2 alkyl-heterocyde-R.sup.25,
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- R.sup.24 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.25 is selected from R.sup.25 ', ##STR3564## R.sup.25 ' is selected from the group SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkylamine,
- C.sub.2 -C.sub.6 alkenylamine, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl
- where any alkyl or alkenyl moiety is optionally substituted with
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26, and
- NR.sup.27 R.sup.28, and
- where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
- R.sup.26 is selected from
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkanoyl;
- R.sup.27 and R.sup.28 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- phenyl,
- napthyl,
- benzyl,
- CH.sub.2 napthyl (.alpha. or .beta.)
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 cycloaLkanoyl.
- C6-C.sub.10 aroyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkylsulfonyl,
- C.sub.6 -C.sub.10 arylsulfonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
- cinnamoyl,
- heterocydecarbonyl,
- C.sub.1 -C.sub.6 alkoxycarbonyl,
- C.sub.6 -C.sub.10 aryloxycarbonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
- pyroglutamyl;
- R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3565## a cyclic imide represented by ##STR3566## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0,1,or 2, and NR.sup.28 ;
- J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
- R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl; and
- pharmaceutically acceptable salts thereof.
- 8. A compound represented by structural formula (III): ##STR3567## where R and R' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkoxy,
- hydroxy,
- hydroxy-C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkylcarbonyl, and
- C.sub.1 -C.sub.6 alkyloxycarbonyl;
- R.sup.1 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and ##STR3568## R.sup.4 and R.sup.4 ' are independently selected from the group hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- phenyl, and
- benzyl;
- W is selected from the group
- C(.dbd.O)--NR.sup.7 'R.sup.8,
- CH.sub.2 --C(.dbd.O)--NRR.sup.8,
- C(.dbd.O)--O--R.sup.8,
- CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '-CHR.sup.7 R.sup.8,
- CR.sup.8 '.dbd.--CR.sup.7 R.sup.8 (E or Z),
- C(.dbd.O)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--NR.sup.7 'R.sup.8,
- CHR.sup.8 '--O--R.sup.8
- CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0, 1, or 2,
- CR.sup.8 '.dbd.N--R.sup.8,
- CHR.sup.8 --R.sup.8,
- W',
- C.sub.1 -C.sub.3 alkyl-W',
- C.sub.6 -C.sub.12 aryl-W',
- C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl-W',
- heterocyde-W',
- heterocycle-C.sub.1 -C.sub.3 alkyl-W',
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-W', and
- C.sub.1 -C.sub.2 alkyl-heterocycle-W', and
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- W' is selected from one to three substituents selected from the group
- hydrogen,
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- R.sup.8, and
- V;
- R.sup.7, each occurance, is independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.4 alkyl,
- halo(F, Cl, Br, I), and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.7 ' is selected from the group
- hydrogen,
- C.sub.1 -C.sub.4 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a pyrrolidinyl or piperidyl ring optionally substituted with one or two groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl,
- C.sub.2 -C.sub.8 alkenyl,
- C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
- where any aryl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- NH--C(.dbd.NH)--NH.sub.2,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- V is selected from the group
- COR.sup.10,
- SO.sub.3 R.sup.13,
- NHSO.sub.2 CF.sub.3,
- PO(OR.sup.13)2,
- SO.sub.2 NHR.sup.10,
- CONHOR.sup.13,
- C(OH)R.sup.10 PO(OR.sup.13)2,
- halo(F, Cl, Br, I),
- NO.sub.2,
- CN,
- SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxyl,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- CONHSO.sub.2 R.sup.15,
- SO.sub.2 NHCOR.sup.15,
- CONHSO.sub.2 R.sup.13,
- CH.sub.2 CONHSO.sub.2 R.sup.15,
- NHCONHSO.sub.2 R.sup.15,
- NHSO.sub.2 NHCOR.sup.15,
- CONHNHSO.sub.2 CF.sub.3,
- CON(OH)R.sup.13,
- CONHCOCF.sub.3,
- CONHSO.sub.2 R.sup.10,
- CONHSO.sub.2 R.sup.11,
- CONHSO.sub.2 R.sup.13, ##STR3569## R.sup.9 is selected from the group hydrogen,
- methyl,
- ethyl,
- isopropyl,
- t-butyl,
- phenyl, and
- benzyl;
- R.sup.10 is selected from the group
- hydroxy,
- C.sub.1 -C.sub.8 -alkoxy,
- C.sub.3 -C.sub.12 -alkenoxy,
- C.sub.6 -C.sub.12 -aryloxy,
- C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 -aryloxy,
- di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
- alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
- acetylaminoethoxy,
- nicotinoylaminoethoxy, and
- succinamidoethoxy,
- C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino,
- hydroxy-C.sub.2 -C.sub.8 -alkoxy,
- dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
- NR.sup.11 R.sup.12 ;
- R.sup.11 and R.sup.12 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino, and
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
- nitro,
- halo(F, Cl, Br, I), and
- C.sub.1 -C.sub.4 -alkoxy;
- R.sup.13 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
- phenyl,
- benzyl, and
- CH.sub.2 COCH.sub.3 ;
- R.sup.15 is selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl, where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxyl,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- C.sub.3 -C.sub.7 -cyloalkyl,
- C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl as defined above,
- OH,
- SH,
- C.sub.1 -C.sub.4 -alkyl,
- C.sub.1 -C.sub.4 -alkoxy,
- C.sub.1 -C.sub.4 -alkylthio,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- CO.sub.2 H,
- CO.sub.2 -(C.sub.1 -C.sub.4)-alkyl,
- NH.sub.2,
- N�(C.sub.1 -C.sub.4)-alkyl!.sub.2,
- NH�(C.sub.1 -C.sub.4)-alkyl!,
- PO.sub.3 H, and
- PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
- (C.sub.1 -C.sub.4)-perfluoroalkyl;
- R.sup.16 is selected from the group
- CN,
- NO.sub.2,
- COOR.sup.13,
- C.sub.1 -C.sub.6 -perfluoroalkyl, and
- CF.sub.3 ;
- R.sup.19 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkoxy,
- C.sub.2 -C.sub.6 alkoxyalkyl,
- CH.sub.2 --O--COCH.sub.3, and
- benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from ##STR3570## R.sup.25 is selected from the group SR.sup.26 ,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkylamine,
- C.sub.2 -C6alkenylamine, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- where any alkyl or alkenyl moiety is optionally substituted with
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26, and
- NR.sup.27 R.sup.28, and
- where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
- R.sup.26 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkanoyl;
- R.sup.27 and R.sup.28 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- phenyl,
- napthyl,
- benzyl,
- CH.sub.2 napthyl (.alpha. or .beta.),
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 cycloalkanoyl,
- C.sub.6 -C.sub.10 aroyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkylsulfonyl,
- C.sub.6 -C.sub.10 arylsulfonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
- cinnamoyl,
- heterocyclecarbonyl,
- C.sub.1 -C.sub.6 -alkoxycarbonyl,
- C.sub.6 -C.sub.10 aryloxycarbonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
- pyroglutamyl;
- R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3571## and a cyclic imide represented by ##STR3572## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0,1,or 2, and NR.sup.28 ;
- J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
- R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl; and
- pharmaceutically acceptable salts thereof.
- 9. A compound represented by structural formula (IV): ##STR3573## where R and R' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 all,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkoxy,
- hydroxy,
- hydroxy-CC.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkylcarbonyl, and
- C.sub.1 -C.sub.6 alkyloxycarbonyl;
- R.sup.1 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)-C.sub.1 -C.sub.6 alkyl, and ##STR3574## R.sup.4 and R.sup.4 ' are independently selected from the group hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- phenyl, and
- benzyl;
- W is selected from the group
- C(.dbd.O)-NR.sup.7 'R.sup.8,
- CH.sub.2 --C(.dbd.O)-NR.sup.7 'R.sup.8,
- C(.dbd.O)--O--R.sup.8,
- CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--CHR.sup.7 R.sup.8,
- CR.sup.8 '.dbd.CR.sup.7 R.sup.8 (E or Z),
- C(.dbd.O)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--NR.sup.7 'R.sup.8,
- CHR.sup.8 '--O--R.sup.8,
- CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0, 1, or 2,
- CR.sup.8 '.dbd.N--R.sup.8,
- CHR.sup.8 '--R.sup.8,
- C.sub.1 -C.sub.3 alkyl-W',
- C.sub.6 -C.sub.12 aryl-W',
- C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl-W',
- heterocyde-W',
- heterocycle-C.sub.1 -C.sub.3 alkyl-W',
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-W', and
- C.sub.1 -C.sub.2 alkyl-heterocyle-W', and
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- W' is selected from one to three substituents selected from the group
- hydrogen,
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- R.sup.8, and
- V;
- R.sup.7, each occurance, is independently selected from the group
- hydrogen,
- C.sub.1-C.sub.4 alkyl,
- halo(F, Cl, Br, I), and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.7 ' is selected from the group
- hydrogen,
- C.sub.1 -C.sub.4 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a pyrrolidinyl or piperidyl ring optionally substituted with one or two groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl,
- C.sub.2 -C.sub.8 alkenyl,
- C.sub.6 -C.sub.12 arylC.sub.1 -C.sub.3 alkyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
- where any aryl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- NH--C(.dbd.NH)--NH.sub.2,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- V is selected from the group
- COR.sup.10,
- SO.sub.3 R.sup.13,
- NHSO.sub.2 CF.sub.3,
- PO(OR.sup.13)2,
- SO.sub.2 NHR.sup.10,
- CONHOR.sup.13,
- C(OH)R.sup.10 PO(OR.sup.13)2,
- CN,
- SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the
- NO.sub.2,
- NHO.sub.2,
- OH, and
- OCH.sub.3 ; ##STR3575## represents a heterocycle bonded to the benzodiazepine moiety through a spiro linkage, where the heterocycle is a 5- or 6-member saturated or unsaturated nitrogen containing ring having from 0 to 2 additional heteroatoms selected from O, N, and S, the ring optionally containing a keto �--C(.dbd.O)--! group;
- X' is selected from the group
- C(.dbd.O)--R.sup.25,
- CH(OH)--R.sup.25,
- CHR.sup.24 --R.sup.25,
- S(O).sub.u --R.sup.25 where u is 0, 1, or 2,
- CHR.sup.24 --R.sup.25,
- R.sup.25,
- C.sub.6 -C.sub.10 aryl-R.sup.25,
- heterocyle-R.sup.25,
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
- C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25,
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- R.sup.24 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.25 is selected from R.sup.25, ##STR3576## heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C4alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- CONHSO.sub.2 R.sup.15,
- SO.sub.2 NHCOR.sup.15,
- CONHSO.sub.2 R.sup.13,
- CH.sub.2 CONHSO.sub.2 R.sup.15,
- NHCONHSO.sub.2 R.sup.15,
- NHSO.sub.2 NHCOR.sup.15,
- CONHNHSO.sub.2 CF.sub.3,
- CON(OH)R.sup.13,
- CONHCOCF.sub.3,
- CONHSO.sub.2 R.sup.10,
- CONHSO.sub.2 R.sup.11,
- CONHSO.sub.2 R.sup.13, ##STR3577## R.sup.9 is selected from the group hydrogen,
- methyl,
- ethyl,
- isopropyl,
- t-bytyl,
- phenyl, and
- benzyl;
- R.sup.10 is selected from the group
- hydroxy,
- C.sub.1 -C.sub.8 -alkoxy,
- C.sub.3 -C.sub.12 -alkenoxy,
- C.sub.6 -C.sub.12 -aryloxy,
- C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 -aryloxy,
- di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
- alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
- acetylaminoethoxy,
- nicotinoylaminoethoxy, and
- succinamidoethoxy,
- C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino,
- hydroxy-C.sub.2 -C.sub.8 -alkoxy,
- dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
- NR.sup.11 R.sup.12 ;
- R.sup.11 and R.sup.12 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.2 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino, and
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
- nitro,
- halo(F, Cl, Br, I), and
- C.sub.1 -C.sub.4 -alkoxy;
- R.sup.13 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
- phenyl,
- benzyl, and
- CH.sub.2 --O--COCH.sub.3 ;
- R.sup.15 is selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl, where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- C.sub.3 -C.sub.7 -cycloalkyl,
- C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl as defined above,
- OH,
- SH,
- C.sub.1 -C.sub.4 -alkyl,
- C.sub.1 -C.sub.4 -alkoxy,
- C.sub.1 -C.sub.4 -alkylthio,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- CO.sub.2 H,
- CO.sub.2 --(C.sub.1 -C.sub.4)--alkyl,
- NH.sub.2,
- N�(C.sub.1 -C.sub.4)-alkyl!.sub.2,
- NH�(C.sub.1 -C.sub.4)-alkyl!,
- PO.sub.3 H, and
- PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
- (C.sub.1 -C4)-perfluoroalkyl;
- R.sup.16 is selected from the group
- CN,
- NO.sub.2,
- COOR.sup.13,
- C.sub.1 -C.sub.6 -perfluoroalkyl, and
- CF.sub.3 ;
- R.sup.19 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkeny,
- C.sub.1 -C.sub.6 alkoxy,
- C.sub.2 -C.sub.6 aloxyalkyl,
- CH.sub.2 --O--COCH.sub.3, and
- benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from
- NO.sub.2,
- NH.sub.2,
- OH, and
- OCH.sub.3 ; ##STR3578## represents a heterocycle fused to the benzodiazepine moiety, where the heterocycle is a 5- or 6-member saturated or unsaturated di-nitrogen containing ring having from 0 to 1 additional heteroatom selected from O, N, and S, the ring optionally containing a keto �--C(.dbd.O)--! group;
- X' is selected from the group
- C(.dbd.O)--R.sup.25,
- CH(OH)--R.sup.25,
- CHR.sup.24 --R.sup.25,
- S(O).sub.u --R.sup.25 where u is 0,1, or 2,
- CHR.sup.24 --R.sup.25,
- R.sup.25,
- C.sub.6 -C.sub.10 aryl--R.sup.25
- heterocyle-R.sup.25,
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl--R.sup.25, and
- C.sub.1 -C.sub.2 alkyl-heterocyle-R.sup.25,
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- R.sup.24 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.25 is selected from R.sup.25 ', ##STR3579## R.sup.25 ' is selected from the group SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkylamine,
- C.sub.2 -C.sub.6 alkenylamine, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- where any alkyl or alkenyl moiety is optionally substituted with
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26, and
- NR.sup.27 R.sup.28, and
- where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
- R.sup.26 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 akanoyl;
- R.sup.27 and R.sup.28 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- phenyl,
- napthyl,
- benzyl,
- CH.sub.2 napthyl (.alpha. or .beta.),
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 cycloalkanoyl,
- C.sub.6 -C.sub.10 aroyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkylsulfonyl,
- C.sub.6 -C.sub.10 arylsulfonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
- cinnamoyl,
- heterocyclecarbonyl,
- C.sub.1 -C.sub.6 alkoxycarbonyl,
- C.sub.6 -C.sub.10 aryloxycarbonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
- pyroglutamyl;
- R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3580## and a cyclic imide represented by ##STR3581## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0, 1, or 2, and NR.sup.28 ;
- J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
- R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl; and
- pharmaceutically acceptable salt thereof.
- 10. A compound represented by structural formula (V): ##STR3582## where R and R' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkoxy,
- hydroxy,
- hydroxy-C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkylcarbonyl, and
- C.sub.1 -C.sub.6 alkyloxycarbonyl;
- R.sup.1 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl, and ##STR3583## R.sup.4 is selected from the group hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- phenyl, and
- benzyl;
- R.sup.7 is selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- A.sup.1 and A.sup.2 are independently selected from the group
- CRR',
- CR',
- CRR.sup.8,
- CR.sup.8,
- N,
- O, and
- S, and
- provided one of A.sup.1 and A.sup.2 is CRR.sup.8 or CR.sup.8 ;
- represents a single or double bond;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl,
- C.sub.2 -C.sub.8 alkenyl,
- phenyl-C.sub.1 -C.sub.3 alkyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
- where any phenyl moiety is optionally substituted with OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- NH--C(.dbd.NH)--NH.sub.2,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- V is selected from the group
- COR.sup.10,
- SO.sub.3 R.sup.3,
- NHSO.sub.2 CF.sub.3,
- PO(OR.sup.13).sub.2,
- SO.sub.2 NHR.sup.10,
- CONHOR.sup.13,
- C(OH)R.sup.10 PO(OR.sup.13).sub.2,
- CN,
- SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2, and
- CONHSO.sub.2 R.sup.15,
- SO.sub.2 NHCOR.sup.15,
- CONHSO.sub.2 R.sup.13,
- CH.sub.2 CONHSO.sub.2 R.sub.15,
- NHCONHSO.sub.2 R.sup.15,
- NHSO.sub.2 NHCOR.sup.15,
- CONHNHSO.sub.2 CF.sub.3,
- CON(OH)R.sup.13,
- CONHCOCF.sub.3,
- CONHSO.sub.2 R.sup.10,
- CONHSO.sub.2 R.sup.11,
- CONHSO.sub.2 R.sup.13, ##STR3584## R.sup.9 is selected from the group hydrogen,
- methyl,
- ethyl,
- isopropyl,
- t-butyl,
- phenyl, and
- benzyl;
- R.sup.10 is selected from the group
- hydroxy,
- C.sub.1 -C.sub.8 -alkoxy,
- C.sub.3 -C.sub.12 -alkenoxy,
- C.sub.6 -C.sub.12 -aryloxy,
- C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.8 -alkoxy,
- di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
- alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
- acetylaminoethoxy,
- nicotinoylaminoethoxy, and
- succinamidoethoxy,
- C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino,
- hydroxy-C.sub.2 -C.sub.8 -alkoxy,
- dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
- NR.sup.11 R.sup.12 ;
- R.sup.11 and R.sup.12 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino, and
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from the group
- nitro,
- halo(F, Cl, Br, I), and
- C.sub.1 -C.sub.4 -alkoxy;
- R.sup.13 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
- phenyl,
- benzyl, and
- CH.sub.2 --O--COCH.sub.3 ;
- R.sup.15 is selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- C.sub.3 -C.sub.7 -cyloalkyl,
- C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl as defined above,
- OH,
- SH,
- C.sub.1 -C.sub.4 -alkyl,
- C.sub.1 -C.sub.4 -alkoxy,
- C.sub.1 -C.sub.4 -alkylthio,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- CO.sub.2 H,
- CO.sub.2 (C.sub.1 -C.sub.4)alkyl,
- NH.sub.2,
- N�(C.sub.1 -C.sub.4)-alkyl!.sub.2,
- NH�(C.sub.1 -C.sub.4)-alkyl!,
- PO.sub.3 H or
- PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
- (C.sub.1 -C.sub.4)-perfluoroalkyl;
- R.sup.16 is selected from the group
- CN,
- NO.sub.2,
- COOR.sup.13,
- C.sub.1 -C.sub.6 -perfluoroalkyl, and
- CF.sub.3 ;
- R.sup.19 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkoxy,
- C.sub.2 -C.sub.6 alkoxyalkyl,
- CH.sub.2 --O--COCH.sub.3, and
- benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from
- NO.sub.2,
- NH.sub.2,
- OH, and
- OCH.sub.3 ;
- X is selected from the group
- NR.sup.24 --C(.dbd.O)--R.sup.25,
- NR.sup.24 --CH(OH)--R.sup.25,
- NR.sup.24 --CH.sub.2 --R.sup.25,
- NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0, 1, or 2,
- CHR.sup.24 --CH.sub.2 R.sup.25,
- CHR.sup.24 --R.sup.25,
- CR.sup.24 .dbd.CHR.sup.25 (E or Z),
- C.sub.6 -C.sub.10 aryl- R.sup.25,
- heterocycle-R.sup.25,
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
- C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25, and
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- R.sup.24 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.25 is selected from R.sup.25 ', ##STR3585## R.sup.25 ' is selected from the group SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkylamine,
- C.sub.2 -C.sub.6 alkenylamine, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- where any alkyl or alkenyl moiety is optionally substituted with
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26 and
- NR.sup.27 R.sup.28, and
- where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
- R.sup.26 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkanoyl;
- R.sup.27 and R.sup.28 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- phenyl,
- napthyl,
- benzyl,
- CH.sub.2 napthyl (.alpha. or .beta.),
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 cycloalkanoyl,
- C.sub.6 -C.sub.10 aroyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkylsulfonyl,
- C.sub.6 -C.sub.10 arylsulfonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
- cinnamoyl,
- heterocyclecarbonyl,
- C.sub.1 -C.sub.6 alkoxycarbonyl,
- C.sub.6 -C.sub.10 aryloxycarbonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
- pyroglutamyl;
- R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3586## and a cyclic imide represented by ##STR3587## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0,1,or 2, and NR.sup.28 ;
- J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
- R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl; and
- pharmaceutically acceptable salts thereof.
- 11. A compound represented by structural formula (VI): ##STR3588## where R and R' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkoxy,
- hydroxy,
- hydroxy-C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkylcarbonyl, and
- C.sub.1 -C.sub.6 alkyloxycarbonyl;
- R.sup.1 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)-C.sub.1 -C.sub.6 alkyl, and ##STR3589## R.sup.4 and R.sup.4 ' are independently selected from the group hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- phenyl, and
- benzyl;
- W is selected from the group
- C(.dbd.O)--NR.sup.7 '.sup.8,
- CH.sub.2 --C(.dbd.O)--NR.sup.7 'R.sup.8,
- C(.dbd.O)--O--R.sup.8,
- CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--CHR.sup.7 R.sup.8,
- CR.sup.8 '.dbd.CR.sup.7 R.sup.8 (E or Z),
- C(.dbd.O)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--NR7'R.sup.8,
- CHR.sup.8 '--O--R.sup.8,
- CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0,1, or 2,
- CR.sup.8 '.dbd.N--R.sup.8,
- CHR.sup.8 '--R.sup.8,
- W',
- C.sub.1 -C.sub.3 alkyl-W',
- C.sub.6 -C.sub.12 aryl-W',
- C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl-W',
- heterocyde-W',
- heterocycle-C.sub.1 -C.sub.3 alkyl-W',
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-W', and
- C.sub.1 C.sub.2 alkyl-heterocyde-W',
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- W' is selected from one to three substituents selected from the group
- hydrogen,
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- R.sup.8, and
- V;
- R.sup.7, each occurance, is independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.4 alkyl, halo(F, Cl, Br, I), and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.7 ' is selected from the group
- hydrogen,
- C.sub.1 -C.sub.4 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a pyrrolidinyl or piperidyl ring optionally substituted with one or two groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl,
- C.sub.2 -C.sub.8 alkenyl,
- phenyl-C.sub.1 C.sub.3 alkyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
- where any phenyl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- NH--C(.dbd.NH)--NH.sub.2,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- V is selected from the group
- COR.sup.10,
- SO.sub.3 R.sup.13,
- NHSO.sub.2 CF.sub.3,
- PO(OR.sup.13).sub.2,
- SO.sub.2 NHR.sup.10,
- CONHOR.sup.13,
- C(OH)R.sup.10 PO(OR.sup.13).sub.2,
- CN,
- SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2, and
- CONHSO.sub.2 R.sup.15,
- SO.sub.2 NHCOR.sup.15,
- CONHSO.sub.2 R.sup.13,
- CH.sub.2 CONHSO.sub.2 R.sup.15,
- NHCONHSO.sub.2 R.sup.15,
- NHSO.sub.2 NHCOR.sup.15,
- CONHNHSO.sub.2 CF.sub.3,
- CON(OH)R.sup.13,
- CONHCOCF.sub.3,
- CONHSO.sub.2 R.sup.10,
- CONHSO.sub.2 R.sup.11,
- CONHSO.sub.2 R.sup.13, ##STR3590## R.sup.9 is selected from the group hydrogen,
- methyl,
- ethyl,
- isopropyl,
- t-butyl,
- phenyl, and
- benzyl;
- R.sup.10 is selected from the group
- hydroxy,
- C.sub.1 -C.sub.8 -alkoxy,
- C.sub.3 -C.sub.12 -alkenoxy,
- C.sub.6 -C.sub.12 -aryloxy,
- C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 -aryloxy,
- di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
- alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
- acetylaminoethoxy,
- nicotinoylaminoethoxy, and
- succinamidoethoxy, and
- C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino, and
- hydroxy-C.sub.2 -C.sub.8 -alkoxy,
- dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
- NR.sup.11 R.sup.12 ;
- R.sup.11 and R.sup.12 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alanoyl substituted with from one to three groups selected from
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino, and
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
- nitro,
- halo(F, Cl, Br, I), and
- C.sub.1 -C.sub.4 -alkoxy;
- R.sup.13 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)-C.sub.1 -C.sub.6 alkyl,
- phenyl,
- benzyl, and
- CH.sub.2 --O--COCH.sub.3 ;
- R.sup.15 is selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- C.sub.3 -C.sub.7 -cycloalkyl,
- C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from
- C.sub.6 -C.sub.14 aryl,
- heteroaryl as defined above,
- OH,
- SH,
- C.sub.1 -C.sub.4 -alkyl,
- C.sub.1 C4-alkoxy,
- C.sub.1 -C.sub.4 -alkylthio,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- CO.sub.2 H,
- CO.sub.2 -(C.sub.1 -C.sub.4)-alkyl,
- NH.sub.2,
- N�(C.sub.1 -C.sub.4)-alkyl!.sub.2,
- NH�(C.sub.1 -C.sub.4)-alkyl!,
- PO.sub.3 H, and
- PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
- (C.sub.1 -C.sub.4)-perfluoroalkyl;
- R.sup.16 is selected from the group
- CN,
- NO.sub.2,
- COOR.sup.13,
- C.sub.1 -C.sub.6 -perfluoroalkyl, and
- CF.sub.3 ;
- R.sup.19 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkoxy,
- (C.sub.2 -C.sub.6)-alkoxyalkyl,
- CH.sub.2 --O--COCH.sub.3, and
- benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from the group
- NO.sub.2,
- NH.sub.2,
- OH, and
- OCH.sub.3 ; ##STR3591## represents a heterocycle bonded to the benzodiazepine moiety through a ring nitrogen, where the heterocycle is a 5- or 6-member saturated or unsaturated nitrogen containing ring having from 0 to 2 additional heteroatoms selected from O, N, and S, the ring optionally containing a keto �--C(.dbd.O)--! group;
- R.sup.25 ' is selected from the group
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkylamine,
- C.sub.2 -C.sub.6 alkenylamine, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- where any alkyl or alkenyl moiety is optionally substituted with
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26 and
- NR.sup.27 R.sup.28, and
- where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
- R.sup.26 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkanoyl;
- R.sup.27 and R.sup.28 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- phenyl,
- napthyl,
- benzyl,
- CH.sub.2 napthyl (.alpha. or .beta.)
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 cycloalkanoyl,
- C.sub.6 -C.sub.10 aroyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkylsulfonyl,
- C.sub.6 -C.sub.10 arylsulfonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkycarbamoyl,
- cinnamoyl,
- heterocyclecarbonyl,
- C.sub.1 -C.sub.6 alkoxycarbonyl,
- C.sub.6 -C.sub.10 aryloxycarbonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
- pyroglutamyl;
- R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3592## or a cyclic imide represented by ##STR3593## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0,1,or 2, and NR.sup.28 ;
- J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene; and
- pharmaceutically acceptable salts thereof.
- 12. A compound represented by structural formula (VII): ##STR3594## where R and R' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkoxy,
- hydroxy,
- hydroxy-C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkykarbonyl, and
- C.sub.1 -C.sub.6 alkyloxycarbonyl;
- R.sup.4 and R.sup.4 ' are independentl y selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- phenyl, and
- benzyl;
- R.sup.7 is selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- W is selected from the group the group
- C(.dbd.O)--NR.sup.7 'R.sup.8,
- CH.sub.2 --C(.dbd.O)--NR.sup.7 'R.sup.8,
- C(.dbd.O)--O--R.sup.8,
- CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--CHR.sup.7 R.sup.8,
- CR.sup.8 '.dbd.CR.sup.7 R.sup.8 (E or Z),
- C(.dbd.O)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--NR.sup.7 'R.sup.8,
- CHR.sup.8 '--O--R.sup.8,
- CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0, 1, or 2,
- CR.sup.8 '.dbd.N--R.sup.8,
- CHR.sup.8 '--R.sup.8,
- W',
- C.sub.1 -C.sub.3 alkyl-W',
- C.sub.6 -C.sub.12 aryl-W',
- C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl-W',
- heterocycle-W',
- heterocyde-C.sub.1 -C.sub.3 alkyl-W',
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-W', and
- C.sub.1 -C.sub.2 alkyl-heterocycle-W', and
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- W' is selected from one to three substituents selected from the group
- hydrogen,
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- R.sup.8 and
- V;
- R.sup.7, each occurance, is independently selected from the group
- hydrogen,
- C.sub.1 C.sub.4 alkyl,
- halo(F, Cl, Br, I), and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.7 ' is selected from the group
- hydrogen,
- C.sub.1 -C.sub.4 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a pyrrolidinyl or piperidyl ring optionally substituted with one or two groups selected from the group
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl,
- C.sub.2 -C.sub.8 alkenyl,
- phenyl-C.sub.1 -C.sub.3 alkyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
- where any phenyl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- NH--C(.dbd.NH)--NH.sub.2,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- V is selected from the group
- COR.sup.10,
- SO.sub.3 R.sup.13,
- NHSO.sub.2 CF.sub.3,
- PO(OR.sup.13).sub.2,
- SO.sub.2 NHR.sup.10,
- CONHOR.sup.13,
- C(OH)R.sup.10 PO(OR.sup.13).sub.2,
- CN,
- SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- CONHSO.sub.2 R.sup.15,
- SO.sub.2 NHCOR.sup.15,
- CONHSO.sub.2 R.sup.13,
- CH.sub.2 CONHSO.sub.2 R.sup.15,
- NHCONHSO.sub.2 R.sup.15,
- NHSO.sub.2 NHCOR.sup.15,
- CONHNSO.sub.2 CF.sub.3,
- CON(OH)R.sup.13,
- CONHCOCF.sub.3,
- CONHSO.sub.2 R.sup.10,
- CONHSO.sub.2 R.sup.11,
- CONHSO.sub.2 R.sup.13, ##STR3595## R.sup.9 is selected from the group hydrogen,
- methyl,
- ethyl,
- isopropyl,
- t-butyl,
- phenyl, and
- benzyl;
- R.sup.10 is selected from the group
- hydroxy,
- C.sub.1 -C.sub.8 -alkoxy,
- C.sub.3 -C.sub.12 -alkenoxy,
- C.sub.6 -C.sub.12 -aryloxy,
- C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 -aryloxy,
- di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
- alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
- acetylaminoethoxy,
- nicotinoylaminoethoxy, and
- succiamidoethoxy,
- C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C4-alkoxy, and
- amino,
- hydroxy-C.sub.2 -C.sub.8 -alkoxy,
- dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
- NR.sup.11 R.sup.12 ;
- R.sup.11 and R.sup.12 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino, and
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
- nitro,
- halo(F, Cl, Br, I), and
- C.sub.1 -C.sub.4 -alkoxy;
- R.sup.13 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
- phenyl,
- benzyl, and
- CH.sub.2 --O--COCH.sub.3 ;
- R.sup.15 is selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2, and
- C.sub.3 -C.sub.7 - cyloalkyl ,
- C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl as defined above,
- OH,
- SH,
- C.sub.1 -C.sub.4 -alkyl,
- C.sub.1 -C.sub.4 -alkoxy,
- C.sub.1 -C.sub.4 -alkylthio,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- CO.sub.2 H,
- CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl,
- NH.sub.2,
- N�(C.sub.1 -C.sub.4)-alkyl!.sub.2,
- NH�(C.sub.1 -C.sub.4)-alkyl!,
- PO.sub.3 H or
- PO(OH)(C.sub.1 -C.sub.4 -alkoxy, and
- (C.sub.1 -C.sub.4)-perfluoroalkyl;
- R.sup.16 is selected from the group
- CN,
- NO,
- COOR.sup.13,
- C.sub.1 -C.sub.6 -perfluoroalkyl, and
- CF.sub.3 ;
- R.sup.19 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkoxy,
- C.sub.2 -C.sub.6 alkoxyalkyl,
- CH.sub.2 --O--COCH.sub.3, and
- benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from
- NO.sub.2,
- NH.sub.2,
- OH, and
- OCH.sub.3 ;
- X is selected from the group
- NR.sup.24 --C(.dbd.O)--R.sup.25,
- NR.sup.24 --CH(OH)--R.sup.25,
- NR.sup.24 --CH.sub.2 --R.sup.25,
- NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0, 1, or 2,
- CHR.sup.24 --CH.sub.2 R.sup.25,
- CHR.sup.24 --R.sup.25,
- CR.sup.24 .dbd.CHR.sup.25 (E or Z),
- C.sub.6 -C.sub.10 aryl-R.sup.25,
- heterocycle-R.sup.25,
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25, and
- C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25, and
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- R.sup.24 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.25 is selected from R.sup.25 ', ##STR3596## R.sup.25 ' is selected from the group SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkylamine,
- C.sub.2 -C.sub.6 alkenylamine, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- where any alkyl or alkenyl moiety is optionally substituted with
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26 and
- NR.sup.27 R.sup.28, and
- where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
- R.sup.26 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl, halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkanoyl;
- R.sup.27 and R.sup.28 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- phenyl,
- napthyl,
- benzyl,
- CH.sub.2 napthyl (.alpha. or .beta.)
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 cycloalkanoyl,
- C.sub.6 -C.sub.10 aroyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alanoyl,
- C.sub.1 -C.sub.6 alkylsulfonyl,
- C.sub.6 -C.sub.10 arylsulfonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
- cinnamoyl,
- heterocyclecarbonyl,
- C.sub.1 -C.sub.6 alkoxycarbonyl,
- C.sub.6 -C.sub.10 aryloxycarbonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
- pyroglutamyl;
- R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amine represented by ##STR3597## and a cyclic imide represented by ##STR3598## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0, 1, or 2, and NR.sup.28 ;
- J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
- R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl; and
- pharmaceutically acceptable salts thereof.
- 13. A compound represented by structural formula (VIII): ##STR3599## where R.sup.1 is selected from the group
- CF.sub.3 and ##STR3600## R and R' are independently selected from the group hydrogen,
- halo (F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkoxy,
- hydroxy,
- hydroxy-C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkylcarbonyl, and
- C.sub.1 -C.sub.6 alkyloxycarbonyl;
- R.sup.4 and R.sup.4 ' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- phenyl, and
- benzyl;
- R.sup.7 is selected from the group
- hydrogen
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl; ##STR3601## represents C.sub.6 -C.sub.10 aryl or a heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S, the C.sub.6 -C.sub.10 aryl or heteroaryl is optionally substituted with V and R.sup.8 ;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl,
- phenyl-C.sub.1 -C.sub.3 alkyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
- where any phenyl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- NH--C(.dbd.NH)--NH.sub.2,
- C(.dbd.O)NHOH,
- NHR.sub.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- V is selected from the group
- COR.sup.10,
- SO.sub.3 R.sup.13,
- NHSO.sub.2 CF.sub.3,
- PO(OR.sup.13).sub.2,
- SO.sub.2 NHR.sup.10,
- CONHOR.sup.13,
- C(OH)R.sup.10 PO(OR.sup.13).sub.2,
- CN,
- SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- CONHSO.sub.2 R.sup.15,
- SO.sub.2 NHCOR.sup.15,
- CONHSO.sub.2 R.sup.13,
- CH.sub.2 CONHSO.sub.2 R.sup.15,
- NHCONHSO.sub.2 R.sup.15,
- NHSO.sub.2 NHCOR.sup.15,
- CONHNHSO.sub.2 CF.sub.3,
- CON(OH)R.sup.13,
- CONHCOCF.sub.3,
- CONHSO.sub.2 R.sup.10,
- CONHSO.sub.2 R.sup.11,
- CONHSO.sub.2 R.sup.13, ##STR3602## R.sup.9 is selected from the group hydrogen,
- methyl,
- ethyl,
- isopropyl,
- phenyl, and
- benzyl;
- R.sup.10 is selected from the group
- hydroxy,
- C.sub.1 -C.sub.8 -alkoxy,
- C.sub.3 -C.sub.12 -alkenoxy,
- C.sub.6 -C.sub.12 -aryloxy,
- C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.2 -aryloxy,
- di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
- alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
- acetylaminoethoxy,
- nicotinoylaminoethoxy, and
- succinamidoethoxy,
- C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino,
- hydroxy-C.sub.2 -C.sub.8 -alkoxy,
- dihydroxy-C.sub.3 -C.sub.8 -alkoxy, and
- NR.sup.11 R.sup.12 ;
- R.sup.11 and R.sup.12 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino, and
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
- nitro,
- halo(F, Cl, Br, I), and
- C.sub.1 -C.sub.4 -alkoxy;
- R.sup.13 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
- phenyl,
- benzyl, and
- CH.sub.2 --O--COCH.sub.3 ;
- R.sup.15 is selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- C.sub.3 -C.sub.7 -cydoalkyl,
- C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl as defined above,
- OH,
- SH,
- C.sub.1 -C.sub.4 -alkyl,
- C.sub.1 -C.sub.4 -alkoxy,
- C.sub.1 -C.sub.4 -alkylthio,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- CO.sub.2 H,
- CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl,
- NH.sub.2,
- N�(C.sub.1 -C.sub.4)-alkyl!.sub.2,
- NH�(C.sub.1 -C.sub.4)-alkyl!,
- PO.sub.3 H, and
- PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
- (C.sub.1 -C.sub.4)-perfluoroalkyl;
- R.sup.16 is selected from the group
- CN,
- NO.sub.2,
- COOR.sup.13,
- C.sub.1 -C.sub.6 -perfluoroalkyl, and
- CF.sub.3 ;
- R.sup.19 is selected from the group
- hydrogen,
- (C.sub.1 -C.sub.6)-alkyl,
- (C.sub.2 -C.sub.6)-alkenyl,
- (C.sub.1 -C.sub.6)-alkoxy,
- (C.sub.2 -C.sub.6)-alkoxyalkyl,
- CH.sub.2 --O--COCH.sub.3, or
- benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from
- NO.sub.2,
- NH.sub.2,
- OH, or
- OCH.sub.3 ;
- X is selected from the group
- NR.sup.24 --C(.dbd.O)--R.sup.25,
- NR.sup.24 --CH(OH)--R.sup.25,
- NR.sup.24 --CH.sub.2 --R.sup.25,
- NR.sup.24 --S(O).sub.u --R.sup.25 where u is 0,1, or 2,
- CHR.sup.24 --CH.sub.2 R.sup.25,
- CHR.sup.24 --R.sup.25,
- CR.sup.24 .dbd.CHR.sup.25 (E or Z),
- C.sub.6 -C.sub.10 aryl-R.sup.25,
- heterocycle-R.sup.25,
- C.sub.1 -C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-R.sup.25,
- C.sub.1 -C.sub.2 alkyl-heterocycle-R.sup.25, and
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- R.sup.24 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 aLkyl, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl;
- R.sup.25 is selected from R.sup.25, ##STR3603## R.sup.25 ' is selected from the group SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkylamine,
- C.sub.2 -C.sub.6 alkenylamine, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- where any alkyl or alkenyl moiety is optionally substituted with
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26 and
- NR.sup.27 R.sup.28, and
- where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
- R.sup.26 is selected from
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkanoyl;
- R.sup.27 and R.sup.28 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- phenyl,
- napthyl,
- benzyl,
- CH.sub.2 napthyl (.alpha. or .beta.)
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 cycloalkanoyl,
- C.sub.6 -C.sub.10 aroyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkylsulfonyl,
- C.sub.6 -C.sub.10 arylsulfonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
- cinnamoyl,
- heterocyclecarbonyl,
- C.sub.1 -C.sub.6 alkoxycarbonyl,
- C.sub.6 -C.sub.10 aryloxycarbonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
- pyroglutamyl;
- R.sup.27 and R.sup.28 together with the nitrogen atom to which they are bonded may form a cyclic amime represented by ##STR3604## and a cyclic imide represented by ##STR3605## G is selected from --CH.sub.2 --, O, S(O).sub.u where u is 0,1,or 2, and NR.sup.28
- J-M is selected from C.sub.2 -C.sub.4 alkylene and C.sub.2 -C.sub.4 alkenylene;
- R.sup.29 is selected from hydrogen and C.sub.1 -C.sub.3 alkyl; and
- pharmaceutically acceptable salts thereof.
- 14. A compound represented by structural formula (IXa)-(IXd): ##STR3606## where R and R' are independently selected from the group
- hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkoxy,
- hydroxy,
- hydroxy-C.sub.1 -C.sub.6 alkyl,
- C.sub.1 -C.sub.6 alkylcarbonyl, and
- C.sub.1 -C.sub.6 alkyloxycarbonyl;
- R.sup.1 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl, and ##STR3607## R.sup.4 and R.sup.4 ' are independently selected from the group hydrogen,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- phenyl, and
- benzyl;
- W is selected from the group
- C(.dbd.O)--NR.sup.7 'R.sup.8,
- CH.sub.2 --C(.dbd.O)NR.sup.7 'R.sup.8,
- C(.dbd.O)--O--R.sup.8,
- CR.sup.8 '(OH)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--CHR.sup.7 R.sup.8,
- CR.sup.8 '.dbd.CR.sup.7 R.sup.8 (E or Z),
- C(.dbd.O)--CHR.sup.7 R.sup.8,
- CHR.sup.8 '--NR.sup.7 'R.sup.8,
- CHR.sup.8 '--O--R.sup.8,
- CHR.sup.8 '--S(O).sub.u --R.sup.8 where u is 0,1, or 2,
- CR.sup.8 '.dbd.N--R.sup.8,
- CHR.sup.8 '--R.sup.8,
- W',
- C.sub.l -C.sub.3 alkyl-W',
- C.sub.6 -C.sub.12 aryl-W',
- C.sub.6 -C.sub.12 aryl-C.sub.1 -C.sub.3 alkyl-W',
- heterocycle-W',
- heterocyde-C.sub.1 -C.sub.3 alkyl-W',
- C.sub.1 C.sub.2 alkyl-C.sub.6 -C.sub.10 aryl-W', and
- C.sub.1 -C.sub.2 alkyl-heterocycle-W',
- where any heterocycle is a 5- or 6-member saturated or unsaturated ring containing 1 to 3 heteroatoms selected from O, N, and S;
- W' is selected from one to three substituents selected from the group
- hydrogen,
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- R.sup.8, and
- V;
- R.sup.7, each occurance, is independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.4 alkyl,
- halo(F, Cl, Br, I), and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.7 ' is selected from the group
- hydrogen,
- C.sub.1 -C.sub.4 alkyl, and
- halo(F, CL Br, I)C.sub.1 -C.sub.4 alkyl;
- R.sup.7 ' and R.sup.8 together with the nitrogen to which they are bonded may form a pyrrolidinyl or piperidyl ring optionally substituted with one or two groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.O)--R.sup.9,
- OR.sup.9,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- R.sup.8 is selected from the group unsubstituted and substituted
- C.sub.1 -C.sub.8 alkyl,
- C.sub.2 -C.sub.8 alkenyl,
- phenyl-C.sub.1 -C.sub.3 alkyl,
- indol-3-yl-C.sub.1 -C.sub.3 alkyl, and
- imidazol-4-yl-C.sub.1 -C.sub.3 alkyl,
- where any phenyl moiety is optionally substituted with --OR.sup.9 and V, and where any alkyl or alkenyl group is optionally substituted with one to three groups selected from
- SR.sup.9,
- SSR.sup.9,
- SC(.dbd.P)--R.sup.9,
- OR.sup.9,
- C(.dbd.NH)--NH.sub.2,
- N.dbd.CH--NH.sub.2,
- NH--CH.dbd.NH,
- NH--C(.dbd.NH)--NH.sub.2,
- C(.dbd.O)NHOH,
- NHR.sup.9,
- C(.dbd.O)NR.sup.27 R.sup.28, and
- V;
- V is selected from the group
- COR.sup.10,
- SO.sub.3 R.sup.13,
- NHSO.sub.2 CF.sub.3,
- PO(OR.sup.13).sub.2,
- SO.sub.2 NHR.sup.10,
- CONHOR.sup.13,
- C(OH)R.sup.10 PO(OR.sup.13).sub.2,
- CN,
- SO.sub.2 NH-heteroaryl where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2,
- CONHSO.sub.2 R.sup.15,
- SO.sub.2 NHCOR.sup.15,
- CONHSO.sub.2 R.sup.13,
- CH.sub.2 CONHSO.sub.2 R.sup.15,
- NHCONHSO.sub.2 R.sup.15,
- NHSO.sub.2 NHCOR.sup.15,
- CONHNHSO.sub.2 CF.sub.3,
- CON(OH)R.sup.13,
- CONHCOCF.sub.3,
- CONHSO.sub.2 R.sup.10,
- CONHSO.sub.2 R.sup.11,
- CONHSO.sub.2 R.sup.13, ##STR3608## R.sup.9 is selected from the group hydrogen,
- methyl,
- ethyl,
- isopropyl,
- t-butyl,
- phenyl, and
- benzyl;
- R.sup.10 is selected from the group
- hydroxy,
- C.sub.1 -C.sub.8 -alkoxy,
- C.sub.3 -C.sub.12 -alkenoxy,
- C.sub.6 -C.sub.12 -arYloxy,
- C.sub.1 -C.sub.6 -alkyl-C.sub.6 -C.sub.12 -ayloxy,
- di-C.sub.1 -C.sub.8 -alkylamino-C.sub.1 -C.sub.8 -alkoxy,
- alkanoylamino-C.sub.1 -C.sub.8 -alkoxy selected from the group
- acetylaninoethoxy,
- nicotinoylaminoethoxy, and
- succinamidoethoxy, and
- C.sub.1 -C.sub.8 -alkanoyloxy-C.sub.1 -C.sub.8 -alkoxy,
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkoxy where the aryl group is unsubstituted or substituted with one to three of the groups
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and amino, and
- hydroxy-C.sub.2 -C.sub.8 -alkoxy,
- dihydroxy-C.sub.3 -C8-alkoxy, and
- NR.sup.11 R.sup.12 ;
- R.sup.1 land R.sup.12 are independently selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 alkanoyl substituted with from one to three groups selected from
- nitro,
- halo(F, Cl, Br, I),
- C.sub.1 -C.sub.4 -alkoxy, and
- amino, and
- C.sub.6 -C.sub.12 -aryl-C.sub.1 -C.sub.8 -alkyl where the aryl group is unsubstituted or substituted with one to three of the groups selected from
- nitro,
- halo(F, Cl, Br, I),and
- C.sub.1 -C.sub.4 -alkoxy;
- R.sup.13 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- halo(F, Cl, Br, I)--C.sub.1 -C.sub.6 alkyl,
- phenyl,
- benzyl, and
- CH.sub.2 --O--COCH.sub.3 ;
- R.sup.15 is selected from the group
- C.sub.6 -C.sub.14 aryl,
- heteroaryl,where the heteroaryl is a 5- or 6-member aromatic ring containing 1 to 3 heteroatoms selected from O, N, and S and where the heteroaryl is unsubstituted or substituted with one or two substituents selected from the group
- OH,
- SH,
- C.sub.1 -C.sub.4 alkyl,
- C.sub.1 -C.sub.4 alkoxy,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- COOH,
- COO--(C.sub.1 -C.sub.4 alkyl),
- NH.sub.2,
- NH(C.sub.1 -C.sub.4 alkyl), and
- N(C.sub.1 -C.sub.4 alkyl).sub.2, and
- C.sub.3 -C.sub.7 -cycloalkyl,
- C.sub.1 -C.sub.4 -alkyl, unsubstituted or substituted with a substituent selected from
- C.sub.6 -C.sub.14 aryl,
- heteroaryl as defined above,
- OH,
- SH,
- C.sub.1 -C.sub.4 -alkyl,
- C.sub.1 -C.sub.4 -alkoxy,
- C.sub.1 -C.sub.4 -alkylthio,
- CF.sub.3,
- halo(F, Cl, Br, I),
- NO.sub.2,
- CO.sub.2 H,
- CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl,
- NH.sub.2,
- N�(C.sub.1 -C.sub.4)-alkyl!.sub.2,
- NH�(C.sub.1 -C.sub.4)-alkyl!,
- PO.sub.3 H, and
- PO(OH)(C.sub.1 -C.sub.4)-alkoxy, and
- (C.sub.1 -C.sub.4)-perfluoroalkyl;
- R.sup.16 is selected from the group
- CN,
- NO.sub.2,
- COOR.sup.13,
- C.sub.1 -C.sub.6 -perfluoroalkyl, and
- CF.sub.3 ;
- R.sup.19 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C.sub.6 alkoxy,
- (C.sub.2 -C.sub.6)-alkoxyalkyl,
- CH.sub.2 --O--COCH.sub.3, and
- benzyl, where the phenyl moiety is unsubstituted or substituted with a group selected from the group
- NO.sub.2,
- NH.sub.2,
- OH, and
- OCH.sub.3 ;
- R25' is selected from the group
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26,
- C.sub.1 -C.sub.6 alkyl,
- C.sub.2 -C.sub.6 alkenyl,
- C.sub.1 -C6alkylamine,
- C.sub.2 -C.sub.6 alkenylamine, and
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl,
- where any alkyl or alkenyl moiety is optionally substituted with
- SR.sup.26,
- SSR.sup.26,
- OR.sup.26,
- NOR.sup.26 and
- NR.sup.27 R.sup.28, and
- where any amine moiety is optionally substituted with R.sup.27 or R.sup.28 ;
- R.sup.26 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl
- halo(F, Cl, Br, I)C.sub.1 -C.sub.6 alkyl, and
- C.sub.1 -C.sub.6 alkanoyl;
- R.sup.28 is selected from the group
- hydrogen,
- C.sub.1 -C.sub.6 alkyl,
- phenyl,
- napthyl,
- benzyl,
- CH.sub.2 napthyl (.alpha. or .beta.)
- C.sub.1 -C.sub.6 alkanoyl,
- C.sub.1 -C.sub.6 cycloalkanoyl,
- C.sub.6 -C.sub.10 aroyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alanoyl,
- C.sub.1 -C.sub.6 alkylsulfonyl,
- C.sub.6 -C.sub.10 arylsulfonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkylcarbamoyl,
- cinnamoyl,
- heterocyclecarbonyl,
- C.sub.1 -C.sub.6 alkoxycarbonyl,
- C.sub.6 -C.sub.10 aryloxycarbonyl,
- C.sub.6 -C.sub.10 arylC.sub.1 -C.sub.6 alkoxycarbonyl, and
- pyroglutamyl; and
- pharmaceutically acceptable salts thereof.
- 15. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and the compound of claim 1.
- 16. A method of inhibiting farnesyl:protein transferse comprising administering to a subject in need of such treatment a therapeutically effective amount of the composition of claim 15.
- 17. A method of inhibiting farnesylation of the oncogene protein ras comprising administering to a mammal in need of such treatment a therapeutically effective amount of the composition of claim 15.
Parent Case Info
This application is a 371 of PCT/Ser. No. 94/05157, filed May 10, 1994, which is a continuation in part of Ser. No. 08/082,202, filed Jun. 24, 1993; now abandoned, which is a continuation in part of Ser. No. 08/061,961, filed May 15, 1993, now abandoned.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US94/05157 |
5/10/1994 |
|
|
9/26/1994 |
9/26/1994 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO94/26723 |
11/24/1994 |
|
|
US Referenced Citations (14)
Foreign Referenced Citations (1)
Number |
Date |
Country |
166357 |
Jan 1986 |
EPX |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
82202 |
Jun 1993 |
|
Parent |
61961 |
May 1993 |
|