Discovery of 3,4-Dihydropyrimidin-2(1H)-ones As a Novel Class of Potent and Selective A2B Adenosine Receptor Antagonists

被引：65

作者：

Crespo, Abel ^{[1
,2
]}

El Maatougui, Abdelaziz ^{[1
,2
]}

Biagini, Pierfrancesco ^{[2
]}

Azuaje, Jhonny ^{[1
,2
]}

Coelho, Alberto ^{[1
,3
]}

Brea, Jose ^{[2
]}

Isabel Loza, Maria ^{[2
]}

Isabel Cadavid, Maria ^{[2
]}

Garcia-Mera, Xerardo ^{[3
]}

Gutierrez-de-Teran, Hugo ^{[4
]}

Sotelo, Eddy ^{[1
,2
,3
]}

机构：

[1] Univ Santiago de Compostela, Ctr Res Biol Chem & Mol Mat CIQUS, Santiago De Compostela 15782, Spain

[2] Univ Santiago de Compostela, Inst Ind Pharm, Fac Pharm, Santiago De Compostela 15782, Spain

[3] Univ Santiago de Compostela, Dept Organ Chem, Fac Pharm, Santiago De Compostela 15782, Spain

[4] Uppsala Univ, Biomed Ctr, Dept Cell & Mol Biol, SE-75124 Uppsala, Sweden

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2013年 / 4卷 / 11期

关键词：

Adenosine antagonists; A(2B) receptor antagonists; 3,4-dihydropyrimidin-2(1H)-ones; Biginelli reaction; SOLVENT-FREE SYNTHESIS; BIGINELLI; ACID; CONDENSATION; DERIVATIVES; AFFINITY;

D O I：

10.1021/ml400185v

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We describe the discovery and optimization of 3,4-dihydropyrimidin-2(1H)-ones as a novel family of (nonzanthine) A(2B) receptor antagonists that exhibit an unusually high selectivity profile. The Biginelli-based hit optimization process enabled a thoughtful exploration of the structure-activity and structure-selectivity relationships for this chemotype, enabling the identification of ligands that combine structural simplicity with excellent hA(2B) AdoR affinity and remarkable selectivity profiles.

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页码：1031 / 1036

页数：6

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