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Synthesis and evaluation of cis-3,4-disubstituted piperidines as potent CC chemokine receptor 2 (CCR2) antagonists.

Abstract：

:A series of cis-3,4-disubstituted piperidines was synthesized and evaluated as CC chemokine receptor 2 (CCR2) antagonists. Compound 24 emerged with an attractive profile, possessing excellent binding (CCR2 IC(50)=3.4 nM) and functional antagonism (calcium flux IC(50)=2.0 nM and chemotaxis IC(50)=5.4 nM). Studies to explore the binding of these piperidine analogs utilized a key CCR2 receptor mutant (E291A) with compound 14 and revealed a significant reliance on Glu291 for binding.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Cherney RJ,Nelson DJ,Lo YC,Yang G,Scherle PA,Jezak H,Solomon KA,Carter PH,Decicco CP

doi

10.1016/j.bmcl.2008.07.123

subject

Has Abstract

pub_date

2008-09-15 00:00:00

pages

5063-5

issue

18

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(08)00909-8

journal_volume

18

pub_type

杂志文章

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