Referenced in: none

Automatically associated channels: Kv11.1

Title: Azabenzthiazole inhibitors of leukotriene A₄ hydrolase.

Authors: Virginia M Tanis, Genesis M Bacani, Jonathan M Blevitt, Christa C Chrovian, Shelby Crawford, Aimee De Leon, Anne M Fourie, Laurent Gomez, Cheryl A Grice, Krystal Herman, Aaron M Kearney, Adrienne M Landry-Bayle, Alice Lee-Dutra, Jay Nelson, Jason P Riley, Alejandro Santillan, John J M Wiener, Xiaohua Xue, Arlene L Young

Journal, date & volume: Bioorg. Med. Chem. Lett., 2012 Dec 15 , 22, 7504-11

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23127888

Abstract
Previously, benzthiazole containing LTA(4)H inhibitors were discovered that were potent (1-3), but were associated with the potential for a hERG liability. Utilizing medicinal chemistry first principles (e.g., introducing rigidity, lowering cLogD) a new benzthiazole series was designed, congeners of 1-3, which led to compounds 7a, 7c, 12a-d which exhibited LTA(4)H IC(50)=3-6 nM and hERG Dofetilide Binding IC(50)=8.9-> >10 μM.