C-19 Steroids for Inhibiting Neovascularization

The compound defined by the formula 1

• wherein
• a, b and c respectively denote, independently from each other, a single bond or a double bond, with the proviso that at least one of a, b and c represents a double bond, and
• with the proviso that if a is single bond and b is double bond, R2 is not H;
• R1 is either hydrogen or C1 to C6 alkyl;
• R2 is either OR5 or hydrogen, wherein R5 is hydrogen or C1 to C12 straight chain or branched alkyl;
• R3 is, in case of c being a single bond, either hydrogen or C1 to C6 alkyl, or in case of c being a double bond, CHR5, wherein R5 is the same as defined before;
• R4 is hydrogen, C1 to C12 alkyl, phenyl unsubstituted or substituted by C1 to C12 alkyl or COR6 acyl group;
• R6 being hydrogen, C1 to C12 straight chain or branched alkyl, phenyl or benzoyl, respectively, unsubstituted or substituted by C1 to C12 alkyl, or any group
• leading to hydroxyl upon biological metabolization or chemical deprotection, particularly an ester, ether, acetale, carbonate, carbamate, phosphate, phosphonate, ketal, sulfate, or sulfonate, and salts thereof, for use in the therapy of inflammation and/or cancer by inhibiting the proliferation or synthesis of, either alone or in combination:
• endothelial cell proliferation, smooth muscle cell proliferation, endothelial cell migration, smooth muscle cell proliferation, vascular endothelial growth factor, vascular endothelial growth factor receptor, fibroblast growth factor receptor 13, platelet derived growth factor receptor a and/or B, and mast/stem cell growth factor receptor.

A combination comprising:

• (i) an active substance selected from the group consisting of antibodies directed against VEGF, VEGFR or soluble VEGFRNEGFR hybrids, and tyrosine kinase inhibi-tors, and (ii) a compound defined by the formula 1
• wherein
• a, b and c respectively denote, independently from each other, a single bond or a double bond, with the proviso that at least one of a, b and c represents a double bond, and with the proviso that if a is single bond and b is double bond, R2 is not H;
• R1 is either hydrogen or C1 to C6 alkyl;
• R2 is either OR5 or hydrogen, wherein R5 is hydrogen or C1 to C12 straight chain or branched alkyl;
• R3 is, in case of c being a single bond, either hydrogen or C1 to C6 alkyl, or in case of c being a double bond, CHR5, wherein R5 is the same as defined before;
• R4 is hydrogen, C1 to C12 alkyl, phenyl unsubstituted or substituted by C1 to C12 alkyl or COR6 acyl group;
• R6 being hydrogen, C1 to C12 straight chain or branched alkyl, phenyl or benzoyl, respectively, unsubstituted or substituted by C1 to C12 alkyl, or any group leading to hydroxyl upon biological metabolization or chemical deprotection, particularly an ester, ether, acetale, carbonate, carbamate, phosphate, phosphonate, ketal, sulfate, or sulfonate, and salts thereof.