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Design and synthesis of potent, selective phenylimidazole-based FVIIa inhibitors.

Abstract：

:Heterocyclic amide isosteres were incorporated into a phenylglycine-based tissue factor/factor VIIa (TF-FVIIa) inhibitor chemotype, providing potent inhibitors. An X-ray co-crystal structure of phenylimidazole 19 suggested that an imidazole nitrogen atom effectively mimics an amide carbonyl, while the phenyl ring forms key hydrophobic interactions with the S1' pocket. Exploration of phenylimidazole substitution led to the discovery of potent, selective and efficacious inhibitors of TF-FVIIa.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Glunz PW,Cheng X,Cheney DL,Weigelt CA,Wei A,Luettgen JM,Wong PC,Wexler RR,Priestley ES

doi

10.1016/j.bmcl.2015.03.062

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

2169-73

issue

10

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)00268-1

journal_volume

25

pub_type

杂志文章

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