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

作者：Crespo Abel; El Maatougui Abdelaziz; Biagini Pierfrancesco; Azuaje Jhonny; Coelho Alberto; Brea Jose; Isabel Loza Maria; Isabel Cadavid Maria; Garcia Mera Xerardo; Gutierrez de Teran Hugo; Sotelo Eddy^*

来源：ACS Medicinal Chemistry Letters, 2013, 4(11): 1031-1036.

DOI：10.1021/ml400185v

• Adenosine antagonists
• A(2B) receptor antagonists
• 3,4-dihydropyrimidin-2(1H)-ones
• Biginelli reaction

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.

• 出版日期2013-11