Studies on topical antiinflammatory agents. I. Synthesis and vasoconstrictive activity of corticosteroid 17-succinyl esters.

A series of 17-succinyl derivatives of four corticosteroids was prepared. They were tested for vasoconstrictive activity in humans, using 9 alpha-fluoro-11 beta, 21-dihydroxy-16 beta-methyl-17 alpha-valeryloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV) as a standard. The activities of the 21-chloro 17-methylsuccinate compounds (6A, 6C and 6D) were greater than that of BV. A structure-activity relationship study showed that the activities of the 21-chloro 17-methylsuccinates were more potent than those of the corresponding 21-esters.