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Design, synthesis, and biological activity of novel tetrahydropyrazolopyridone derivatives as FXa inhibitors with potent anticoagulant activity.

Abstract：

:A series of novel tetrahydropyrazolopyridone derivatives containing 1,3,4-triazole, triazolylmethyl, and partially saturated heterocyclic moieties as P2 binding element was designed, synthesized, and evaluated in vitro for anticoagulant activity in human and rabbit plasma. All compounds showed moderate to significant potency, and compounds 15b, 15c, 20b, 20c, and 22b were further examined for their inhibitory activity against human FXa in vitro. While compounds 15c and 22b were tested for rat venous thrombosis in vivo. The most promising compound 15c, with an IC50 (FXa) value of 0.14μM and 98% inhibition rate, warranted further investigation as an FXa inhibitor.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Sun X,Hong Z,Liu M,Guo S,Yang D,Wang Y,Lan T,Gao L,Qi H,Gong P,Liu Y

doi

10.1016/j.bmc.2017.03.055

subject

Has Abstract

pub_date

2017-05-15 00:00:00

pages

2800-2810

issue

10

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(17)30420-0

journal_volume

25

pub_type

杂志文章

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