Synthesis and biological evaluation of BMS-986120 and its deuterated derivatives as PAR4 antagonists.

Abstract:

:BMS-986120 is a PAR4 antagonist that is being investigated as an antiplatelet agent in phase I clinical trial. An improved synthesis of BMS-986120 has been developed. Based on the novel synthetic approach to BMS-986120, a series of deuterated derivatives of BMS-986120 have been synthesized and biologically evaluated to search for more potent antiplatelet agents. The in vitro antiplatelet assay by turbidimetry demonstrated that PC-2 and PC-6 had IC50 values of 6.30 nM and 6.97 nM, respectively, versus BMS-986120 with an IC50 of 7.80 nM. The result of in vitro metabolic stability study showed that all of the deuterated compounds had similar half-life (T1/2) and intrinsic clearance (Clint) in comparison with BMS-986120. Further probing the metabolic profile of BMS-986120 is worth being conducted.

journal_name

Bioorg Med Chem

authors

Chen P,Ren S,Song H,Chen C,Chen F,Xu Q,Kong Y,Sun H

doi

10.1016/j.bmc.2018.11.024

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

116-124

issue

1

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(18)31638-9

journal_volume

27

pub_type

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