Examination of local anti-inflammatory activities of new steroids, hemisuccinyl methyl glycolates.

To overcome the side effects of steroids, novel steroid-17-yl methyl glycolates with succinyl group at C-20, derived from predinisolone and dexamethasone were prepared based on concept of the antedrug. Their topical anti-inflammatory activity and systemic effects were evaluated trough croton oil-induced ear edema and paper disk granuloma bioassay. Among them, (20S)-succinyl dexamethasone derivatives (7 and 11) indicated more potent ati-inflammatory activity than the parent dexamethasone and did not show corticosteroidal side effects of thymic, adrenal involution or body weight loss. Both 7 and 11 were immediately metabolized into active compound 3 and this metabolite was eliminated with mean half-lives of 0.786 to 0.866 h in rat serum. Our findings suggest that these two compounds might be candidates as the novel steroids, and that that introduction of the succinyl group into the methyl glycolates at C-20 is useful to avoid suppressiion of organs due to the side effects of corticosteroids.