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Novel Nonsteroidal Progesterone Receptor (PR) Antagonists with a Phenanthridinone Skeleton.
ACS Medicinal Chemistry Letters 2018 July 13
The progesterone receptor (PR) plays an important role in various physiological systems, including female reproduction and the central nervous system, and PR antagonists are thought to be effective not only as contraceptive agents and abortifacients but also in the treatment of various diseases, including hormone-dependent cancers and endometriosis. Here, we identified phenanthridin-6(5 H )-one derivatives as a new class of PR antagonists and investigated their structure-activity relationships. Among the synthesized compounds, 37 , 40 , and 46 exhibited very potent PR antagonistic activity with high selectivity for PR over other nuclear receptors. These compounds are structurally distinct from other nonsteroidal PR antagonists, including cyanoaryl derivatives, and should be useful for further studies of the clinical utility of PR antagonists.
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