New steroidal anti-inflammatory antedrugs: Methyl 3,20-dioxo-9α- fluoro-11β,17α,21-trihy　droxy-1,4- pregnadiene-16α-carboxylate and methyl 21-acetyloxy-3,20-dioxo- 11β,17α-dihydroxy-9α -fluoro-1,4- pregnadiene-16α-carboxylate

摘要

Focused efforts have been made to increase local-to-systemic activity ratios of potent anti-inflammatory steroids for local and/or topical applications. The approach taken in the present investigation is based upon the concept of "antedrug," defined as a locally active compound that exerts its action at the application site but rapidly undergoes a predictable biotransformation to an inactive metabolite that is readily excreted upon entry into the systemic circulation. In continuing efforts to synthesize potent, anti-inflammatory steroids without systemic glucocorticoid activities, 9α-fluoro-methyl 11β,17α, 21-trihydroxy-3,20-dioxo-pregna-1,4-diene- 16a-carboxvlate (FP16CM ) and its 21-acetate derivative (FP16CMAc ) have been synthesized and screened.