Document Report Card
Basic Information
ID: ALA1124725
Journal: J Med Chem
Title: Inhibition of steroid 5 alpha-reductase by unsaturated 3-carboxysteroids.
Authors: Holt DA, Levy MA, Oh HJ, Erb JM, Heaslip JI, Brandt M, Lan-Hargest HY, Metcalf BW.
Abstract: A series of unsaturated steroids bearing a 3-carboxy substituent has been prepared and assayed in vitro as inhibitors of human and rat prostatic steroid 5 alpha-reductase (EC 1.3.1.30). It is proposed that the observed tight binding of the 3-androstene-3-carboxylic acids is due to mimicry of a putative, high-energy, enzyme-bound enolate intermediate formed during the NADPH-dependent conjugate reduction of testosterone by steroid 5 alpha-reductase. These compounds were prepared through palladium(0)-catalyzed carbomethoxylations of enol (trifluoromethyl)sulfonates derived from 3-keto precursors. Modification of A and B ring unsaturation and substitution at C-3, -4, -6, and -11 was explored. Mono- and dialkylcarboxamides were employed as 17 beta side chains to enhance inhibitory activity with the human enzyme.
CiteXplore: 2308145
DOI: 10.1021/jm00165a010