Abstract |
The unique replacements of the alpha- hydroxyl and beta-ketol groups of corticoids at C17 with selected, simple alkylthio or (2-fluoroalkyl)thio groups resulted in the structurally novel steroids, C17-alkylthioketals of 9 alpha-fluoro-11 beta-hydroxy-androsta-1,4-diene-3,17-dione. The described androstene-17-thioketals (20-thiasteroids) had high affinities for the glucocorticoid receptor protein of rat liver cytosol. Most were more potent than triamcinolone acetonide, a clinically moderately potent corticoid, in antiproliferative and antiinflammatory activities in mice. Specifically, (11 beta, 17 alpha)-17-(ethylthio)-9 alpha-fluoro-11 beta-hydroxy-17-(methylthio) androsta-1,4-dien-3-one ( tipredane, SQ 27,239) and (11 beta, 17 alpha)-17-(ethylthio)-9 alpha-fluoro-17-[2-(fluoroethyl)thio] - 11 beta - hydroxy-androsta-1,4-dien-3-one (SQ 28,300), topically applied, were as potent as halcinonide, a clinically highly potent corticoid, in inhibition of croton oil-induced edema in the mouse. It is suggested that both thiasteroids could be moderately to highly potent topical antiinflammatory agents in man.
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Authors | R J Wojnar, R K Varma, C A Free, R C Millonig, D Karanewsky, B N Lutsky |
Journal | Arzneimittel-Forschung
(Arzneimittelforschung)
Vol. 36
Issue 12
Pg. 1782-7
(Dec 1986)
ISSN: 0004-4172 [Print] Germany |
PMID | 3494458
(Publication Type: Journal Article)
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Chemical References |
- Androstenes
- Anti-Inflammatory Agents
- Receptors, Glucocorticoid
- Croton Oil
- DNA
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Topics |
- Adrenalectomy
- Androstenes
(metabolism, pharmacology)
- Animals
- Anti-Inflammatory Agents
(metabolism)
- Cell Division
(drug effects)
- Croton Oil
- DNA
(biosynthesis)
- Dose-Response Relationship, Drug
- Edema
(chemically induced, prevention & control)
- In Vitro Techniques
- Liver
(metabolism)
- Mice
- Rats
- Receptors, Glucocorticoid
(metabolism)
- T-Lymphocytes
(metabolism)
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