A β-tryptase inhibitor with a tropanylamide scaffold to improve in vitro stability and to lower hERG channel binding affinity

G Liang, YM Choi-Sledeski, P Shum, X Chen…

Index: Liang, Guyan; Choi-Sledeski, Yong Mi; Shum, Patrick; Chen, Xin; Poli, Gregory B.; Kumar, Vasant; Minnich, Anne; Wang, Qingping; Tsay, Joseph; Sides, Keith; Kang, Jiesheng; Zhang, Ying Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 4 p. 1606 - 1610

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Citation Number: 5

Abstract

Tropanylamide was investigated as a possible scaffold for β-tryptase inhibitors with a basic benzylamine P1 group and a substituted thiophene P4 group. Comparing to piperidinylamide, the tropanylamide scaffold is much more rigid, which presents less opportunity for the inhibitor to bind with off-target proteins, such as cytochrome P450, SSAO, and hERG potassium channel. The proposed binding mode was further confirmed by an ...