Structure activity relationships of 5-, 6-, and 7-methyl-substituted azepan-3-one cathepsin K inhibitors

…, R Xie, SD Nidamarthy, HJ Oh, JU Jeong…

Index: Yamashita, Dennis S.; Marquis, Robert W.; Xie, Ren; Nidamarthy, Sirishkumar D.; Oh, Hye-Ja; Jeong, Jae U.; Erhard, Karl F.; Ward, Keith W.; Roethke, Theresa J.; Smith, Brian R.; Cheng; Geng, Xiaoliu; Lin, Fan; Offen, Priscilla H.; Wang, Bing; Nevins, Neysa; Head, Martha S.; Haltiwanger, R. Curtis; Sarjeant, Amy A. Narducci; Liable-Sands, Louise M.; Zhao, Baoguang; Smith, Ward W.; Janson, Cheryl A.; Gao, Enoch; Tomaszek, Thaddeus; McQueney, Michael; James, Ian E.; Gress, Catherine J.; Zembryki, Denise L.; Lark, Michael W.; Veber, Daniel F. Journal of Medicinal Chemistry, 2006 , vol. 49, # 5 p. 1597 - 1612

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Citation Number: 55

Abstract

The syntheses, in vitro characterizations, and rat and monkey in vivo pharmacokinetic profiles of a series of 5-, 6-, and 7-methyl-substituted azepanone-based cathepsin K inhibitors are described. Depending on the particular regiochemical substitution and stereochemical configuration, methyl-substituted azepanones were identified that had widely varied cathepsin K inhibitory potency as well as pharmacokinetic properties ...