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ID: ALA3352238

Journal: Bioorg Med Chem Lett

Title: Substituted indoles as selective protease activated receptor 4 (PAR-4) antagonists: Discovery and SAR of ML354.

Authors: Wen W, Young SE, Duvernay MT, Schulte ML, Nance KD, Melancon BJ, Engers J, Locuson CW, Wood MR, Daniels JS, Wu W, Lindsley CW, Hamm HE, Stauffer SR.

Abstract: Herein we report the discovery and SAR of an indole-based protease activated receptor-4 (PAR-4) antagonist scaffold derived from a similarity search of the Vanderbilt HTS collection, leading to MLPCN probe ML354 (VU0099704). Using a novel PAC-1 fluorescent αIIbβ3 activation assay this probe molecule antagonist was found to have an IC50 of 140nM for PAR-4 with 71-fold selectivity versus PAR-1 (PAR-1IC50=10μM).

CiteXplore: 25176330

DOI: 10.1016/j.bmcl.2014.08.021