Method for regressing angiogenesis using o-substituted fumagillol derivatives

A method for regressing angiogenesis in a mammal, which comprises administering an effective amount of an O-substituted fumagillol derivative or a pharmaceutically acceptable salt thereof to the mammal, wherein the O-substituted fumagillol derivative is a compound of the formula:

• ##STR84## wherein R.sup.1 is a 2-methyl-1-propenyl or isobutyl group which may be substituted with a substituent selected from the group consisting of hydroxyl, amino, C.sub.1-3 alkylamino, or di-C.sub.1-3 alkylamino, and R.sup.2 is (1) (i) a carbamoyl group, which may optionally be substituted with from one to two substituents selected from the group consisting of C.sub.1-6 alkyl, C.sub.1-6 alkanoyl, chloroacetyl, dichloroacetyl, trichloroacetyl, C.sub.1-6 alkoxycarbonylmethyl, carboxymethyl, amino, phenyl, wherein the phenyl substituent may be substituted with from one to five substituents selected from the group consisting of C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen, halo-C.sub.1-6 alkyl or nitro, naphthyl, benzoyl, halogenated C.sub.1-6 alkyl, di-C.sub.1-6 alkylamino-C.sub.1-6 alkyl, C.sub.1-6 alkanoyloxy-C.sub.1-6 alkanoyl, C.sub.1-6 alkanoylthio-C.sub.1-6 alkanoyl, C.sub.1-6 alkylthio-C.sub.1-6 alkanoyl, arylthio-C.sub.1-6 alkanoyl, di-C.sub.1-6 alkylamino-C.sub.1-6 alkanoyl, ammonio-C.sub.1-6 alkanoyl.halide, C.sub.1-6 alkoxycarbonyl, phenoxycarbonyl, chloroacetylcarbamoyl, benzoylcarbamoyl, phenylsulfonyl, wherein the phenylsulfonyl substituent may be substituted with from one to five substituents selected from the group consisting of C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen, halo-C.sub.1-6 alkyl or nitro, or di-C.sub.1-6 alkylsulfonio-C.sub.1-6 alkanoyl.halide, or (ii) a cyclic amino-carbonyl group selected from the group consisting of pyrrolidin-1-yl-carbonyl, piperidino-carbonyl, morpholino-carbonyl, piperazin-1-yl-carbonyl, 4-methylpiperazin-1-yl-carbonyl, 4-ethylpiperazin-1-yl-carbonyl, 4-phenylpiperazin-1-yl-carbonyl or imidazol-1-yl-carbonyl;
• (2) an alkyl group, which may optionally be (i) substituted with from one to three substituents selected from the group consisting of amino, C.sub.1-6 alkylamino, di-C.sub.1-6 alkylamino, nitro, halogen, hydroxyl, C.sub.1-6 alkoxy, cyano, carbamoyl, carboxyl, C.sub.1-6 alkoxycarbonyl, carboxy-C.sub.1-6 alkoxy, or phenyl, wherein the phenyl substituent may be substituted with from one to five substituents selected from the group consisting of C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen, halo-C.sub.1-6 alkyl or nitro, or (ii) epoxidized;
• (3) a benzenesulfonyl group, which may be optionally substituted with from one to three substituents selected from the group consisting of C.sub.1-6 alkyl and halogen;
• (4) an alkylsulfonyl group, which may be optionally substituted with from one to three substituents selected from the group consisting of amino, C.sub.1-6 alkylamino, di-C.sub.1-6 alkylamino, nitro, halogen, hydroxyl, C.sub.1-6 alkoxy, cyano, carbamoyl, C.sub.1-6 alkoxycarbonyl, carboxy-C.sub.1-6 alkoxy, and phenyl, wherein the phenyl substituent may be substituted with from one to five substituents selected from the group consisting of C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen, halo-C.sub.1-6 alkyl or nitro;
• (5) a sulfamoyl group, which may optionally be substituted with from one or two substituents selected from the group consisting of C.sub.1-6 alkyl, or phenyl, wherein the phenyl substituent may be substituted with one to five substituents selected from the group consisting of C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen, halo-C.sub.1-6 alkyl and nitro;
• (6) an alkoxycarbonyl group, which may optionally be substituted with halogen;
• or (7) a phenoxycarbonyl group, which may optionally be substituted with from one to three substituents selected from the group consisting of C.sub.1-6 alkyl and halogen;
• or a pharmaceutically acceptable salt thereof.