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Discovery and optimization of a new class of potent and non-chiral indole-3-carboxamide-based renin inhibitors.

Abstract：

:Selective inhibition of the aspartyl protease renin has gained attraction as an interesting approach to control hypertension and associated cardiovascular risk factors given its unique position in the renin-angiotensin system. Using a combination of high-throughput screening, parallel synthesis, X-ray crystallography and structure-based design, we identified and optimized a novel series of potent and non-chiral indole-3-carboxamides with remarkable potency for renin. The most potent compound 5k displays an IC(50) value of 2nM.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Scheiper B,Matter H,Steinhagen H,Stilz U,Böcskei Z,Fleury V,McCort G

doi

10.1016/j.bmcl.2010.08.092

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

6268-72

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(10)01228-X

journal_volume

20

pub_type

杂志文章

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