Document Report Card

ID: ALA1127426

Journal: J Med Chem

Title: Androgen receptor affinity of 5'-acyl furanosteroids.

Authors: Kumar V, Ackerman JH, Alexander MD, Bell MR, Christiansen RG, Dung JS, Jaeger EP, Herrmann JL, Krolski ME, McKloskey P.

Abstract: Syntheses of 5'-acyl furanosteroids are described from the corresponding unsubstituted [3,2-b]furanosteroids using acid anhydrides and acid chlorides in the presence or absence of Lewis acids. New methods have been developed to prepare 5'-acetyl derivatives: reduction of a 5'-trichloroacetyl intermediate either by sodium formaldehyde sulfoxylate or with 10% Pd/C. Most of these 5'-acyl derivatives bind to the rat ventral prostate androgen receptor. However the antiandrogenic activity was diminished when compared with 4,5'-methylsulfonyl furanosteroid. Biological studies revealed that 5'-acyl furanosteroids were either androgens or modest antiandrogens. The electrostatic potential maps of the substructures of 3, 4, and 5'-acetyl syn- and anti-furanosteroids showed striking differences which may explain, to some extent, the lack of significant antiandrogenic activity of 5'-acyl furanosteroids.

CiteXplore: 7990121

DOI: 10.1021/jm00050a019