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 prednisolone and dexamethasone were prepared based on a concept of the antedrug. Their topical anti-inflammatory activity and systemic effects were evaluated through croton oil-induced ear edema and paper disk granuloma bioassay. Among them, (20S)-succinyl dexamethasone derivatives (7 and 11) indicated more potent anti-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 suppression of organs due to the side effects of corticosteroids.
Suzuki
T
T
Department of Pharmaceutical Science, Akita University Hospital, Japan.
Sato
E
E
Tada
H
H
Tojima
Y
Y
D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006016:Glycolates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013057:Spectrum Analysis; D013256:Steroids; D013950:Thymus Gland / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D006016:Glycolates; D013256:Steroids