Referenced in: none

Automatically associated channels: Kv11.1

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

Authors: Guyan Liang, Yong Mi Choi-Sledeski, Patrick Shum, Xin Chen, Gregory B Poli, Vasant Kumar, Anne Minnich, Qingping Wang, Joseph Tsay, Keith Sides, Jiesheng Kang, Ying Zhang

Journal, date & volume: Bioorg. Med. Chem. Lett., 2012 Feb 15 , 22, 1606-10

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22264487

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 in-house X-ray structure through co-crystallization.