Inhibition of steroid 5α-reductase by 3-nitrosteroids: synthesis, mechanism of inhibition, and in vivo activity

A series of A-ring unsaturated 3-nitrosteroids has been prepared and assayed in vitro as inhibitors of steroid 5α-reductase. One of these compounds, 3-nitro-5α-androst-3-ene-17β-diisopropylcarboxamide ( 4), inhibits the human enzyme with a K i of 50 nM and exhibits competitive inhibition versus test...

Full description

Saved in:
Bibliographic Details
Published inBioorganic & medicinal chemistry letters Vol. 1; no. 1; pp. 27 - 32
Main Authors Holt, Dennis A., Levy, Mark A., Yen, Hwa-Kwo, Oh, Hye-Ja, Metcalf, Brian W., Wier, Patrick J.
Format Journal Article
LanguageEnglish
Published Elsevier Ltd 1991
Online AccessGet full text

Cover

More Information
Summary:A series of A-ring unsaturated 3-nitrosteroids has been prepared and assayed in vitro as inhibitors of steroid 5α-reductase. One of these compounds, 3-nitro-5α-androst-3-ene-17β-diisopropylcarboxamide ( 4), inhibits the human enzyme with a K i of 50 nM and exhibits competitive inhibition versus testosterone. Potent oral activity of 4 was demonstrated in cynomolgus monkeys. Nitrosteroid 4 is a potent inhibitor of human steroid 5α-reductase (K i,app=50 nM) which exhibits competitive inhibition kinetics versus testosterone and demonstrates oral efficacy in lowering plasma DHT concentrations in monkeys.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(01)81084-2