Abstract |
4-Substituted N-(1,1-dimethylethyl)-3-oxo-4-androstene-17 beta-carboxamides with the hydroxy ( OH) 3d, mercapto (SH) 3e, chloro (Cl) 3f, and bromo (Br) 3g substituents at the 4-position were prepared in a two-step sequence with overall yields of 21%, 27%, 41%, and 37%, respectively. Compounds 3d-g showed weak inhibitory activity on human type I 5 alpha-reductase (IC50 > or = 700 nM) while they had intermediate inhibitory activity on human type II 5 alpha-reductase at IC50S of 172, 437, 192, and 387 nM, respectively. In androgen-sensitive Shionogi cells, the inhibition of dihydrotestosterone (DHT) stimulatory action on the proliferation of the androgen-sensitive cancer cells by all four compounds was high at IC50S of 170-279 nM compared with 117 nM for hydroxyflutamide. The present data show compounds having both moderate inhibition of human type II 5 alpha-reductase activity and relatively potent antiandrogenic action, two beneficial characteristics in the therapy of androgenic-sensitive diseases.
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Authors | X Li, S M Singh, J Côté, S Laplante, R Veilleux, F Labrie |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 38
Issue 9
Pg. 1456-61
(Apr 28 1995)
ISSN: 0022-2623 [Print] United States |
PMID | 7739004
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 5-alpha Reductase Inhibitors
- Androgen Antagonists
- Androstenes
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Topics |
- 5-alpha Reductase Inhibitors
- Androgen Antagonists
(chemical synthesis, pharmacology)
- Androstenes
(chemical synthesis, pharmacology)
- Animals
- Cell Division
(drug effects)
- Humans
- Mice
- Tumor Cells, Cultured
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