Azepanone-based inhibitors of human cathepsin S: Optimization of selectivity via the P2 substituent

…, W Bondinell, KL Widdowson, DS Yamashita…

Index: Kerns, Jeffrey K.; Nie, Hong; Bondinell, William; Widdowson, Katherine L.; Yamashita, Dennis S.; Rahman, Attiq; Podolin, Patricia L.; Carpenter, Donald C.; Jin, Qi; Riflade, Benoit; Dong, Xiaoyang; Nevins, Neysa; Keller, Paul M.; Mitchell, Laura; Tomaszek, Thaddeus Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 15 p. 4409 - 4415

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Citation Number: 6

Abstract

A series of azepanone inhibitors of cathepsin S is described. Selectivity over both cathepsin K and cathepsin L was achieved by varying the P2 substituent. Ultimately, a balanced potency and selectivity profile was achieved in compound 39 possessing a 1- methylcyclohexyl alanine at P2 and nicotinamide as the P′ substituent. The cellular potency of selected analogs is also described.