Carboxylated, Heteroaryl-Substituted Chalcones as Inhibitors of Vascular Cell Adhesion Molecule-1 Expression for Use in Chronic Inflammatory Diseases
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- 作者：Charles Q. Meng ; Liming Ni ; Kimberly J. Worsencroft ; Zhihong Ye ; M. David Weingarten ; Jacob E. Simpson ; Jason W. Skudlarek ; Elaine M. Marino ; Ki-Ling Suen ; Charles Kunsch ; Amy Souder ; Randy B. Howard
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：March 22, 2007
- 年：2007
- 卷：50
- 期：6
- 页码：1304 - 1315
- 全文大小：193K
- 年卷期：v.50,no.6(March 22, 2007)
- ISSN：1520-4804
文摘
Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series ofcarboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesionmolecule-1 (VCAM-1) expression. Correlations between lipophilicity determined by calculated logP valuesand inhibitory efficacy were observed among structurally similar compounds of the series. Various substituentswere found to be tolerated at several positions of the chalcone backbone as long as the compounds fell intothe right range of lipophilicity. The chalcone 
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-unsaturated ketone moiety seemed to be the pharmacophorerequired for inhibition of VCAM-1 expression. Compound 19 showed significant antiinflammatory effectsin a mouse model of allergic inflammation, indicating that this series of compounds might have therapeuticvalue for human asthma and other inflammatory disorders.
,-unsaturated ketone moiety seemed to be the pharmacophorerequired for inhibition of VCAM-1 expression. Compound 19 showed significant antiinflammatory effectsin a mouse model of allergic inflammation, indicating that this series of compounds might have therapeuticvalue for human asthma and other inflammatory disorders.