Studies on topical antiinflammatory agents. IV. 21-(Alkylthio)acetates and (methylthio)methoxides of corticosteroids.
A series of 21-(alkylthio)acetates and 21-(methylthio)methoxides of corticosteroids were synthesized and examined for vasoconstrictive activities. The activities of seven compounds were equal to or greater than that of 9 alpha-fluoro-11 beta,21-dihydroxy-16 beta-methyl-17 alpha-valeryloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV). Among them, betamethasone 21-(methylthio)acetate 17-propanoate (2Ca) was found to have the most potent activity, which is superior to that of BV. A structure-activity relationship study revealed that substitution of the 21-hydroxy group of corticosteroids with the (methylthio)acetate function is a useful approach for obtaining potent activity.