Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors

DJ Gustin, CA Sehon, J Wei, H Cai, SP Meduna…

Index: Gustin, Darin J.; Sehon, Clark A.; Wei, Jianmei; Cai, Hui; Meduna, Steven P.; Khatuya, Haripada; Sun, Siquan; Gu, Yin; Jiang, Wen; Thurmond, Robin L.; Karlsson, Lars; Edwards, James P. Bioorganic and Medicinal Chemistry Letters, 2005 , vol. 15, # 6 p. 1687 - 1691

Full Text: HTML

Citation Number: 43

Abstract

A novel series of competitive, reversible cathepsin S (CatS) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of CatS inhibitors. This replacement imparted improved PK properties as well as decreased off- target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the ...