title: Studies on topical antiinflammatory agents. III. Synthesis of 17 alpha-acyloxy-9 alpha-fluoro-11 beta-hydroxy-16 beta-methyl-1,4-pregnadiene-3,20-dione 21-thio derivatives and related compounds.
abstract: A series of 21-thio derivatives of 9 alpha-fluoro-11 beta,17 alpha-dihydroxy-16 beta-methyl-1,4-pregnadiene-3, 20-dione 17-esters and related compounds were synthesized and evaluated as topical antiinflammatory agents. These compounds were prepared by the reaction of 9 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-16 beta-methyl-1,4-pregnadiene-3, 20-dione (betamethasone, I) 17-ester derivatives and various mercapto compounds. A structure-activity relationship study revealed that the structural combination of a thio group at the 21-position and an ester group at the 17-position contributed to vasoconstrictive activity. Among these compounds, the 21-methylthio 17-propanoate compound (6) was found to have the most potent activity, being more potent than betamethasone 17-valerate (BV).
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
authors.forename: K
authors.initials: K
authors.lastname: Sota
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001623:Betamethasone / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D055598:Chemical Phenomena; D002621:Chemistry; D009153:Mutagens
chemical_list: D000893:Anti-Inflammatory Agents; D009153:Mutagens; D001623:Betamethasone