Studies on Topical Antiinflammatory Agents. II. Synthesis and Vasoconstrictive Activity of 21-Substituted Corticosteroids with Sulfur-Containing Moieties

As part of the search for new topical antiinflammatory agents, various 21-substituted corticosteroids having sulfur-containing moieties were prepared and tested for vasoconstrictive activity in humans. A structure-activity relationship study revealed that substitution of the 21-hydroxy group with a lower alkyl-thio group enhanced the activity. The activities of the 21-methylthio (3Ad) and the 21-ethylthio (3Ae) compounds were more potent than that of 9α-fluoro-11β, 21-dihydroxy-16β-methyl-17α-valeroyloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV).