Fumagillol derivatives and pharmaceutical compositions thereof

A compound of the formula:

• ##STR86## wherein R.sup.1 is a 2-methyl-1-propenyl or isobutyl group which may be substituted by hydroxyl or di-C.sub.1-3 -alkylamino, and R.sup.2 is
• (1) carbamoyl substituted by
• (i) C.sub.1-6 alkyl which is substituted by halogen, di-C.sub.1-3 -alkylamino, nitro or trimethylammonio halide,
• (ii) C.sub.1-6 alkanoyl which may be substituted by di-C.sub.1-3 alkylamino, nitro, C.sub.1-6 alkyloyloxy, di-C.sub.1-6 alkylthio, C.sub.1-6 alkanoylthio,
• (iii) acryloyl or methacryloyl,
• (iv) phenoxycarbonyl which amy be substituted by halogen or C.sub.1-6 alkyl,
• (v) amino, or
• (vi) carbamoyl which may be substituted by C.sub.1-6 alkanoyl, halo-C.sub.1-6 alkanoyl, naphthyl or benzoyl,
• (2) benzenesulfonyl which may be substituted by C.sub.1-6 alkyl or halogen,
• (3) C.sub.1-6 alkylsulfonyl, or
• (4) sulfamoyl which may be substituted by C.sub.1-6 alkyl or phenyl;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula ##STR87## wherein R.sup.1 is a 2-methyl-1-propenyl or isobutyl group and R.sup.2 is (1) carbamoyl which may be optionally substituted by

• (i) C.sub.1-6 alkyl
• (ii) C.sub.1-6 alkanoyl
• (iii) C.sub.1-6 alkoxycarbonylmethyl
• (iv) carboxymethyl, or
• (v) phenyl which may optionally be substituted by C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen, trifluoromethyl, chloromethyl or nitro, naphthyl, or benzoyl;
• or a pharmaceutically acceptable salt thereof.

A pharmaceutical composition comprising a compound of the formula ##STR88## wherein R.sup.1 is a 2-methyl-1-propenyl or isobutyl group which may be substituted by hydroxyl or di-C.sub.1-3 -alkylamino, and R.sup.2 is

• (1) carbamoyl which may optionally be substituted by
• (i) C.sub.1-6 alkyl which may be substituted by halogen, di-C.sub.1-3 -alkylamino, nitro, C.sub.1-6 alkoxycarbonyl or trimethylammonio halide,
• (ii) C.sub.1-6 alkanoyl which may be substituted by di-C.sub.1-3 alkylamino, nitro, C.sub.1-6 alkanoyloxy, di-C.sub.1-6 alkylthio, C.sub.1-6 alkanoylthio,
• (iii) acryloyl or methacryloyl,
• (iv) phenyl, naphthyl, benzoyl or benzenesulfonyl which may be substituted by halogen, trifluoromethyl, C.sub.1-6 alkyl, di-C.sub.1-3 alkylamino, nitro, C.sub.1-6 alkanoyloxy or
• (v) C.sub.1-6 alkoxycarbonyl
• (vi) phenoxycarbonyl which may be substituted by halogen or C.sub.1-6 -alkyl,
• (vii) amino, or
• (viii) carbamoyl which may be substituted by C.sub.1-6 alkanoyl, halo-C.sub.1-6 alkanoyl, naphthyl or benzoyl,
• (2) benzenesulfonyl which may be substituted by C.sub.1-6 alkyl or halogen,
• (3) C.sub.1-6 alkylsulfonyl, or
• (4) sulfamoyl which may be substituted by C.sub.1-6 alkyl or phenyl;
• or a pharmaceutically acceptable salt thereof;
• and a pharmaceutically acceptable carrier.

A pharmaceutical composition comprising a compound of the formula:

• ##STR89## wherein R.sup.1 is a 2-methyl-1-propenyl or isobutyl group which may be substituted by hydroxyl or di-C.sub.1-3 alkylamino, and R.sup.2 is
• (1) carbamoyl substituted by
• (i) C.sub.1-6 alkyl which is substituted by halogen, di-C.sub.1-3 alkylamino, nitro or trimethylammonio halide,
• (ii) C.sub.1-6 alkanoyl which may be substituted by di-C.sub.1-3 alkylamino, nitro, C.sub.1-6 alkanoyloxy, di-C.sub.1-6 alkylthio, C.sub.1-6 alkanoylthio,
• (iii) acryloyl or methacryloyl,
• (iv) phenoxycarbonyl which may be substituted by halogen or C.sub.1-6 alkyl,
• (v) amino, or
• (vi) carbamoyl which may be substituted by C.sub.1-6 alkanoyl, halo-C.sub.1-6 alkanoyl, naphthyl or benzoyl,
• (2) benzenesulfonyl which may be substituted by C.sub.1-6 alkyl or halogen,
• (3) C.sub.1-6 alkylsulfonyl, or
• (4) sulfamoyl which may be substituted by C.sub.1-6 alkyl or phenyl;
• or a pharmaceutically acceptable salt thereof;
• and a pharmaceutically acceptable carrier.
• (iv) phenyl, naphthyl,

A pharmaceutical composition for the inhibition of angiogenesis in mammals comprising a compound of the formula:

• ##STR90## wherein R.sup.1 is a 2-methyl-1-propenyl or isobutyl group and R.sup.2 is (1) carbamoyl which may be optionally substituted by
• (i) C.sub.1-6 alkyl
• (ii) C.sub.6 alkanoyl
• (iii) C.sub.1-6 alkoxycarbonylmethyl
• (iv) carboxymethyl, or
• (v) phenyl which may optionally be substituted by C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen, trifluoromethyl, chloromethyl or nitro, napthyl, or benzoyl;
• or a pharmaceutically acceptable salt thereof;
• and a pharmaceutically acceptable carrier.