Studies on topical antiinflammatory agents. V. 17-(Alkylthio)- and methoxyalkanoates of corticosteroids.
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.
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* / 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
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D007509:Irritants; D009153:Mutagens; D013256:Steroids; D013440:Sulfides