Studis on Topical Antiinflammatory Agents. III. : Synthesis of 17α-Acyloxy-9α-fluoro-11β-hydroxy-16β-methyl-1, 4-pregnadiene-3, 20-dione 21-Thio Dericatives and Related Compounds

Abstract

A series of 21-thio derivatives of 9α-fluoro-11β, 17α-dihydroxy-16β-methyl-1, 4-pregnadiene-3, 20-dione 17-esters and related compounds were synthesized and evaluated as topical antiinflammatory agents. These compounds were prepared by the reaction of 9α-fluoro-11β, 17α, 21-trihydroxy-16β-methyl-1, 4-pregnadiene-3, 20-dione (betamethasone, I) 17-ester derivatives and various mercapto compounds. A structure-activity relationship study revealed that the structural combination of a thio group at the 21-position and an ester group at the 17-position contributed to vasoconstrictive activity. Among these compounds, the 21-methylthio 17-propanoate compound (6) was found to have the most potent activity, being more potent than betamethasone 17-valerate (BV).