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

ABSTRACT: We describe the discovery and optimization of 3,4-dihydropyrimidin-2(1H)-ones as a novel family of (nonxanthine) A2B 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 hA2B AdoR affinity and remarkable selectivity profiles.

SUBMITTER: Crespo A

PROVIDER: S-EPMC4027370 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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

Crespo Abel A El Maatougui Abdelaziz A Biagini Pierfrancesco P Azuaje Jhonny J Coelho Alberto A Brea José J Loza María Isabel MI Cadavid María Isabel MI García-Mera Xerardo X Gutiérrez-de-Terán Hugo H Sotelo Eddy E

ACS medicinal chemistry letters 20131003 11

We describe the discovery and optimization of 3,4-dihydropyrimidin-2(1H)-ones as a novel family of (nonxanthine) A2B 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 hA2B AdoR affinity and remarkable selectivity profiles. ...[more]

PMID: 24900602

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Primary Amine-Catalyzed Biginelli Reaction for the Enantioselective Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones.

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