Discovery of potent, selective, orally active benzoxazepine-based Orexin-2 receptor antagonists

T Fujimoto, J Kunitomo, Y Tomata, K Nishiyama…

文献索引：Fujimoto, Tatsuhiko; Kunitomo, Jun; Tomata, Yoshihide; Marui, Shogo; Nishiyama, Keiji; Nakashima, Masato; Yoshikubo, Shin-Ichi; Hirai, Keisuke; Hirozane, Mariko Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 21 p. 6414 - 6416

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被引用次数: 19

摘要

During our efforts to identify a series of potent, selective, orally active human Orexin-2 Receptor (OX2R) antagonists, we elucidated structure-activity relationship (SAR) on the 7- position of a benzoxazepine scaffold by utilizing Hammett σp and Hansch-Fujita π value as aromatic substituent constants. The attempts led to the discovery of compound 1m, possessing good in vitro potency with over 100-fold selectivity against OX1R, good ...