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Carboxylated, heteroaryl-substituted chalcones as inhibitors of vascular cell adhesion molecule-1 expression for use in chronic inflammatory diseases.

Abstract：

:Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Correlations between lipophilicity determined by calculated logP values and inhibitory efficacy were observed among structurally similar compounds of the series. Various substituents were found to be tolerated at several positions of the chalcone backbone as long as the compounds fell into the right range of lipophilicity. The chalcone alpha,beta-unsaturated ketone moiety seemed to be the pharmacophore required for inhibition of VCAM-1 expression. Compound 19 showed significant antiinflammatory effects in a mouse model of allergic inflammation, indicating that this series of compounds might have therapeutic value for human asthma and other inflammatory disorders.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Meng CQ,Ni L,Worsencroft KJ,Ye Z,Weingarten MD,Simpson JE,Skudlarek JW,Marino EM,Suen KL,Kunsch C,Souder A,Howard RB,Sundell CL,Wasserman MA,Sikorski JA

doi

10.1021/jm0614230

subject

Has Abstract

pub_date

2007-03-22 00:00:00

pages

1304-15

issue

6

eissn

0022-2623

issn

1520-4804

journal_volume

50

pub_type

杂志文章

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