Angiogenesis inhibitory agent

Claim 1

A pharmaceutical composition for use as angiogenesis inhibitor in the therapy of inflammatory disease, diabetic retinopathy and cancer in mammals comprising a compound of the formula wherein R¹ is a 2-methyl-1-propenyl or isobutyl group which may be substituted with hydroxyl, amino, (C₁₋₃) alkylamino or di (C₁₋₃) alkylamino, and R² is (1) an C₁₋₂₀ alkanoyl group having one to three substituents each selected from among amino, lower alkylamino, di-(lower alkyl)amino, nitro, halogen, hydroxyl, lower alkoxyl, cyano, carbamoyl, carboxyl, lower alkoxycarbonyl, carboxy-lower alkoxy, phenyl which may optionally be substituted with one to five groups selected from lower alkyl, lower alkoxy, halogen, haloalkyl, and nitro, and 2-furyl, 2-thienyl, 4-thiazolyl, 4-imidazolyl, 4-pyridyl, (2) 2-furoyl, 2-thenoyl, nicotinoyl, isonicotinoyl, imidazole-1-carbonyl, which may optionally be substituted with a substituent or substituents selected from the group consisting of C₂₋₆ alkyl, amino, halogen, hydroxyl, lower alkoxy, cyano, carbamoyl and carboxyl, (3) (i) a carbamoyl group, which may optionally be substituted with one or two groups selected from lower alkyl, alkanoyl containing 1 to 6 carbon atoms, chloroacetyl, dichloroacetyl, trichloroacetyl, lower alkoxycarbonylmethyl, carboxymethyl, amino, phenyl which may optionally be substituted with one to five groups selected from lower alkyl, lower alkoxy, halogen, haloalkyl and nitro, naphthyl, benzoyl, halogenated lower alkyl, di-lower alkylamino-lower alkyl, lower-alkanoyloxy-lower alkanoyl, lower alkanoylthio-lower alkanoyl, lower alkylthio-lower alkanoyl, arylthio-lower alkanoyl, 4-pyridylthioacetyl, 2-pyridylthioacetyl, 2-benzothiazolylthioacetyl, 2-benzoxazolylthioacetyl, 2-benzoimidazolylthioacetyl, 8-quinolylthioacetyl, [1-(2-dimethylaminoethyl)tetrazol]-5-ylthioacetyl, 2-methyl-1,3,4-thiadiazol-5-ylthioacetyl, 1-methyl-2-methoxycarbonyl-1,3,4-triazol-5-ylthioacetyl, N-oxy-2-pyridylthio-lower alkanoyl, N-lower alkyl-4-pyridiniothio-lower alkanoyl · halide, dilower alkylamino-lower alkanoyl, ammonio-lower alkanoyl · halide, 3-furoyl, nicotinoyl, 2-thenoyl, lower alkoxycarbonyl, phenoxycarbonyl, chloroacetylcarbamoyl, benzoylcarbamoyl, phenylsulfonyl which may have substituents selected from lower alkyl, lower alkoxy, halogen, haloalkyl and nitro, and di(lower alkyl) sulfonio-lower alkanoyl · halide, or (ii) a cyclic amino-carbonyl group wherein the cyclic amino group is pyrrolidin-1-yl, piperidino, morpholino, piperazin-1-yl, 4-methylpiperazin-1-yl, 4-ethylpiperazin-1-yl, 4-phenylpiperazin--1-yl or imidazol-1-yl, (4) a straight or branched C₁₋₂₀ alkyl group, which (i) may optionally be substituted with one to three substituents each selected from among those substituents mentioned above for the substituted alkanoyl group in the item (1) and (ii) may be epoxidized at any optional position, (5) a benzenesulfonyl group, which may optionally be substituted with one to three groups selected from lower alkyl and halogen, (6 ) an alkylsulfonyl group, which may optionally be substituted with one to three substituents each selected from among, those substituents mentioned above for the substituted alkanoyl group in the item (1), ( 7) a sulfamoyl group, Which may optionally be substituted with one or two groups selected from lower alkyl, phenyl and phenyl substituted with one to five groups selected from lower alkyl, lower alkoxy, halogen, halo-alkyl and nitro, (8) an alkoxycarbonyl group, which may optionally be substituted with halogen or ( 9 ) a phenoxycarbonyl group, which may optionally be substituted with one to three groups selected from substituents mentioned above for the optionally substituted benzenesulfonyl group in the item (5 ); or a pharmaceutically acceptable salt thereof.