Inhibition of angiogenesis involving the coadministration of steroids with heparin or heparin fragments

Abstract

Abstract A method of inhibiting angiogenesis in a warm blooded animal which comprises administering to said animal an anti-angiogenic effective amount of a compound of the formula: <IMAGE> wherein the dotted line between positions C-1 and C-2 means the presence or absence of a double bond; the DIFFERENCE bond at C-6 denotes alpha or beta ; wherein R1 is CH3 or -C2H5; wherein R2 is H, and R3 is in the alpha -position and is -OH, -O-alkyl(C1-C12), -OC(=O)alkyl(C1-C12), -OC(=O)aryl, -OC(=O)N(R)2, or -OC(=O)OR7, wherein aryl is furyl, thienyl, pyrrolyl, or pyridyl wherein each of said hetero moiety is optionally substituted with one or two (C1-C4)-alkyl groups or aryl is -(CH2)f-phenyl wherein f is 0 to 2 and wherein the phenyl ring is optionally substituted with one to three groups selected from chlorine, fluorine, bromine, alkyl(C1-C3), alkoxy(C1-C3), thioalkoxy(C1-C3), Cl3C-, F3C-, -NH2 and -NHCOCH3 and wherein R is hydrogen, alkyl(C1-C4), or phenyl and each R can be the same or different; and wherein R7 is aryl as herein defined or alkyl(C1-C12); or wherein R2 is alpha -Cl and R3 is beta -Cl; or wherein R2 and R3 taken together are oxygen (-O-) bridging positions C-9 and C-11; or wherein R2 and R3 taken together form a double bond between positions C-9 and C-11; wherein R4 is H, CH3, Cl or F; wherein R5 is H, OH, F, Cl, Br, CH3, phenyl, vinyl or allyl; wherein R6 is H or CH3; wherein R9 is H, OH, CH3+L, F or =CH2; and wherein R10 is H, OH, CH3 or R10 forms a second bond between positions C-16 and C-17.

Inventors

• 👤 John M. Braughler
• 👤 Edward D. Hall
• 👤 John M. McCall
• 👤 Wendell Wierenga
• 👤 Judah Folkman

Bibliographic Details