Studies on topical antiinflammatory agents. IV. 21-(Alkylthio)acetates and (methylthio)methoxides of corticosteroids.
A series of 21-(alkylthio)acetates and 21-(methylthio)methoxides of corticosteroids were synthesized and examined for vasoconstrictive activities. The activities of seven compounds were equal to or greater than 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 them, betamethasone 21-(methylthio)acetate 17-propanoate (2Ca) was found to have the most potent activity, which is superior to that of BV. A structure-activity relationship study revealed that substitution of the 21-hydroxy group of corticosteroids with the (methylthio)acetate function is a useful approach for obtaining potent activity.
Mitsukuchi
M
M
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Ikemoto
T
T
Taguchi
M
M
Higuchi
S
S
Abe
S
S
Yasui
H
H
Hatayama
K
K
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D066298:In Vitro Techniques; D007509:Irritants; D008297:Male; D009153:Mutagens; D051381:Rats; D013256:Steroids; D013440:Sulfides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D014661:Vasoconstriction / Q000187:drug effects
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D007509:Irritants; D009153:Mutagens; D013256:Steroids; D013440:Sulfides