Novel strategies for the design of new potent and selective human A3 receptor antagonists: an update

Current Medicinal Chemistry
Stefano MoroGiampiero Spalluto

Abstract

A computer-aided approach has been developed in order to understand the molecular pharmacology of human A3R, and specifically, to lead to the discovery and structural refinement of new, potent and selective human A3R antagonists. This review focuses on our combined target-based and ligand-based drug design strategy, recently applied to provide more accurate information about the recognition mode on human A3R of some pyrazolotriazolopyrimidine and triazoloquinoxalinone analogs. The 3D rhodopsin-based homology model of human A3R has represented the starting point of our approach. A high throughput molecular docking method on the considered antagonists has allowed us to generate a receptor-based pharmacophore model. A novel "Y-shaped" pharmacophore binding motif has been proposed for both pyrazolotriazolopyrimidine and triazoloquinoxalinone derivatives. Moreover, related receptor-based 3D-QSAR analysis has been carried out to provide a suitable tool for prediction of the antagonists binding affinity on human A3R.

Citations

May 17, 2008·Journal of Computer-aided Molecular Design·Stefano CostanziKenneth A Jacobson
Oct 23, 2009·Journal of Chemical Information and Modeling·Hao FanAndrej Sali
Jan 1, 2007·Expert Opinion on Drug Discovery·Stefano MoroFrancesca Deflorian
Dec 21, 2006·ChemMedChem·Gloria CristalliRosaria Volpini
Jan 10, 2008·Chemical Reviews·Pier Giovanni BaraldiPier Andrea Borea
Dec 29, 2010·Journal of Medicinal Chemistry·Vicente YazijiEddy Sotelo

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