Synthesis of a series of 8-(substituted-phenyl)xanthines and a study on the effects of substitution pattern of phenyl substituents on affinity for adenosine A1 and A2A receptors

被引：22

作者：

Bansal, Ranju ^{[1
]}

Kumar, Gulshan ^{[1
]}

Gandhi, Deepika ^{[1
]}

Young, Louise C. ^{[2
,3
]}

Harvey, Alan L. ^{[2
,3
]}

机构：

[1] Panjab Univ, Univ Inst Pharmaceut Sci, Chandigarh 160014, India

[2] Univ Strathclyde, Strathclyde Inst Drug Res, Glasgow G4 0NR, Lanark, Scotland

[3] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow G4 0NR, Lanark, Scotland

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 05期

关键词：

8-Arylxanthines; Adenosine receptor antagonists; Radioligand binding assays; A(1) and A(2A) adenosine receptors; SELECTIVE ANTAGONISTS; POTENT; 8-CYCLOALKYL-1,3-DIPROPYLXANTHINES; DERIVATIVES;

D O I：

10.1016/j.ejmech.2008.10.017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of 8-(substituted-phenyl)xanthines have been synthesized and compounds were evaluated for their affinity for A(1) and A(2) adenosine receptors (AR) using radioligand binding assays. The effects of varying the positions of 8-phenyl substituents on affinity and selectivity at A(1) and A(2A) adenosine receptors have been studied. Isovanilloid 1,3-dimethyl-8-[4-methoxy-3-(2-morpholin-4-ylethoxy)phenylxanthine (9d) displayed the highest affinity and selectivity towards A(2A) AR subtypes with K-i = 100 nM over A(1) receptors (Ki > 100 mM). It has been observed that substitution pattern on 8-phenyl group greatly affects the affinity and selectivity at adenosine receptors, with A(2A) tolerating bulkier substituents than did A(1) receptors. (C) 2008 Elsevier Masson SAS. All rights reserved.

引用

页码：2122 / 2127

页数：6

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