Steroidal A ring aryl carboxylic acids: a new class of steroid 5 alpha-reductase inhibitors.
A series of 17 beta-carbamoyl-1,3,5(10)-estratriene-3-carboxylic acids has been prepared and evaluated in vitro as inhibitors of human and rat prostatic steroid 5 alpha-reductase (EC 1.3.1.30). Potent inhibition of the human enzyme, in particular, was observed and preliminary studies using rat enzyme suggest that the inhibition results from the formation of an enzyme-NADP(+)-inhibitor complex. The compounds were synthesized from estrone, generally employing a differentiated bis-triflate carbonylation strategy.
Holt
D A
DA
Department of Medicinal Chemistry, Smith Kline & French Laboratories, King of Prussia, Pennsylvania 19406.
Levy
M A
MA
Ladd
D L
DL
Oh
H J
HJ
Erb
J M
JM
Heaslip
J I
JI
Brandt
M
M
Metcalf
B W
BW
D058891:5-alpha Reductase Inhibitors; D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D008297:Male; D011467:Prostate / Q000201:enzymology; D051381:Rats; D013329:Structure-Activity Relationship
D058891:5-alpha Reductase Inhibitors; D002264:Carboxylic Acids