Potent nonsteroidal progesterone receptor agonists: synthesis and SAR study of 6-aryl benzoxazines

P Zhang, EA Terefenko, A Fensome, Z Zhang…

Index: Zhang, Puwen; Terefenko, Eugene A.; Fensome, Andrew; Zhang, Zhiming; Zhu, Yuan; Cohen, Jeffrey; Winneker, Richard; Wrobel, Jay; Yardley, John Bioorganic and Medicinal Chemistry Letters, 2002 , vol. 12, # 5 p. 787 - 790

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Citation Number: 56

Abstract

Novel 6-aryl benzoxazines were prepared and examined as progesterone receptor (PR) modulators. In contrast to the structurally related 6-aryl dihydroquinoline PR antagonists, the 6-aryl benzoxazines were potent PR agonists. Compounds 4e, 5b, and 6a with the 2, 4, 4- trimethyl-1, 4-dihydro-2H-benzo [d][1, 3] oxazine core were the most potent PR agonists in the series with sub-nanomolar activities (EC50 0.20–0.35 nM). Compound 6a was more ...