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(5H)-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.

中文翻译：

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新型非甾体孕酮受体（PR）拮抗剂与蒽醌骨架

孕酮受体（PR）在包括女性生殖和中枢神经系统在内的各种生理系统中起着重要作用，并且PR拮抗剂被认为不仅可以作为避孕药和堕胎药有效，而且还可以治疗包括激素在内的各种疾病依赖性癌症和子宫内膜异位症。在这里，我们确定了菲咯菌素-6（5 H）-一衍生物为一类新的PR拮抗剂，并研究了它们的构效关系。中合成的化合物，37，40，和46表现出非常强的PR拮抗活性，对PR的选择性比其他核受体高。这些化合物在结构上与其他非甾体类PR拮抗剂（包括氰基芳基衍生物）不同，应用于进一步研究PR拮抗剂的临床应用。