title: Steroidal A ring aryl carboxylic acids: a new class of steroid 5 alpha-reductase inhibitors.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Smith Kline & French Laboratories, King of Prussia, Pennsylvania 19406.
authors.forename: D A
authors.initials: DA
authors.lastname: Holt
authors.forename: M A
authors.initials: MA
authors.lastname: Levy
authors.forename: D L
authors.initials: DL
authors.lastname: Ladd
authors.forename: H J
authors.initials: HJ
authors.lastname: Oh
authors.forename: J M
authors.initials: JM
authors.lastname: Erb
authors.forename: J I
authors.initials: JI
authors.lastname: Heaslip
authors.forename: M
authors.initials: M
authors.lastname: Brandt
authors.forename: B W
authors.initials: BW
authors.lastname: Metcalf
mesh_terms: 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
chemical_list: D058891:5-alpha Reductase Inhibitors; D002264:Carboxylic Acids