Optimization of 2-Amino-4,6-diarylpyrimidine-5-carbonitriles as Potent and Selective A<sub>1</sub> Antagonists
Cristina Val, Carlos Rodríguez-García, Rubén Prieto‐Díaz, Abel Crespo, Jhonny Azuaje, Carlos Carbajales, María Majellaro, Alejandro Díaz‐Holguín, José Brea, Marı́a Isabel Loza, Claudia Gioé-Gallo, Marialessandra Contino, Angela Stefanachi, Xerardo García‐Mera, Juan C. Estévez, Hugo Gutiérrez‐de‐Terán, Eddy Sotelo
Abstract
ARs were conveniently interpreted with rigorous free energy perturbation simulations, which started from the receptor-driven docking model that guided the design of these series.
Topics & Concepts
ChemistrySelectivityPyrimidineStereochemistryDocking (animal)Chemical spaceMolecular modelFree energy perturbationStructure–activity relationshipChemical synthesisCombinatorial chemistryComputational chemistryIn vitroMolecular dynamicsDrug discoveryBiochemistryCatalysisMedicineNursingAdenosine and Purinergic SignalingReceptor Mechanisms and SignalingPharmacological Receptor Mechanisms and Effects