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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Steroidal A ring aryl carboxylic acids: a new class of steroid 5 alpha-reductase inhibitors
1Department of Medicinal Chemistry, Smith Kline & French Laboratories, King of Prussia, Pennsylvania 19406.
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.
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