title: Androgen receptor affinity of 5'-acyl furanosteroids.
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.
authors.affiliation: Department of Medicinal Chemistry, Sterling Winthrop Pharmaceutical Research Division, Collegeville, Pennsylvania 19426-0900.
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.forename: J H
authors.initials: JH
authors.lastname: Ackerman
authors.forename: M D
authors.initials: MD
authors.lastname: Alexander
authors.forename: M R
authors.initials: MR
authors.lastname: Bell
authors.forename: R G
authors.initials: RG
authors.lastname: Christiansen
authors.forename: J S
authors.initials: JS
authors.lastname: Dung
authors.forename: E P
authors.initials: EP
authors.lastname: Jaeger
authors.forename: J L
authors.initials: JL
authors.lastname: Herrmann
authors.forename: M E
authors.initials: ME
authors.lastname: Krolski
authors.forename: P
authors.initials: P
authors.lastname: McKloskey
mesh_terms: D000726:Androgen Antagonists / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D005663:Furans / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism*; D013256:Steroids / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000726:Androgen Antagonists; D005663:Furans; D011944:Receptors, Androgen; D013256:Steroids