title: Studies on topical antiinflammatory agents. V. 17-(Alkylthio)- and methoxyalkanoates of corticosteroids.
abstract: As part of our search for new topical antiinflammatory agents, a series of corticosteroid 17-(alkylthio)- and methoxyalkanoate derivatives was prepared and tested for vasoconstrictive activities. Several compounds were proved to have activity superior or comparable to 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 these compounds, 21-chloro-11 beta-hydroxy-17 alpha-(methylthio)acetoxy-4-pregnene-3,20-dione (5Aa) was found to have the most potent activity, being more active than BV. The structure-activity relationships of the series revealed that introduction of a (methylthio)acetate function into the 17-position as well as the 21-position of corticosteroids was effective for enhancing the topical antiinflammatory activity.
authors.affiliation: Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mitsukuchi
authors.forename: T
authors.initials: T
authors.lastname: Ikemoto
authors.forename: M
authors.initials: M
authors.lastname: Taguchi
authors.forename: S
authors.initials: S
authors.lastname: Higuchi
authors.forename: S
authors.initials: S
authors.lastname: Abe
authors.forename: H
authors.initials: H
authors.lastname: Yasui
authors.forename: K
authors.initials: K
authors.lastname: Hatayama
mesh_terms: D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000633:toxicity; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D066298:In Vitro Techniques; D007509:Irritants; D008297:Male; D009153:Mutagens; D011817:Rabbits; D051381:Rats; D013256:Steroids; D013440:Sulfides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D007509:Irritants; D009153:Mutagens; D013256:Steroids; D013440:Sulfides