Androgen receptor affinity of 5'-acyl furanosteroids.
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.
Kumar
V
V
Department of Medicinal Chemistry, Sterling Winthrop Pharmaceutical Research Division, Collegeville, Pennsylvania 19426-0900.
Ackerman
J H
JH
Alexander
M D
MD
Bell
M R
MR
Christiansen
R G
RG
Dung
J S
JS
Jaeger
E P
EP
Herrmann
J L
JL
Krolski
M E
ME
McKloskey
P
P
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
D000726:Androgen Antagonists; D005663:Furans; D011944:Receptors, Androgen; D013256:Steroids