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

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).

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Wen W,Young SE,Duvernay MT,Schulte ML,Nance KD,Melancon BJ,Engers J,Locuson CW 2nd,Wood MR,Daniels JS,Wu W,Lindsley CW,Hamm HE,Stauffer SR

doi

10.1016/j.bmcl.2014.08.021

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

4708-4713

issue

19

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(14)00852-X

journal_volume

24

pub_type

杂志文章

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