Val, Cristina; Rodriguez-Garcia, Carlos; Prieto-Diaz, Ruben; Crespo, Abel; Azuaje, Jhonny; Carbajales, Carlos; Majellaro, Maria; Diaz-Holguin, Alejandro; Brea, Jose M.; Loza, Maria Isabel; Gioe-Gallo, Claudia; Contino, Marialessandra; Stefanachi, Angela; Garcia-Mera, Xerardo; Estevez, Juan C.; Gutierrez-de-Teran, Hugo; Sotelo, Eddy published the artcile< Optimization of 2-Amino-4,6-diarylpyrimidine-5-carbonitriles as Potent and Selective A1 Antagonists>, Recommanded Product: 3-(3-Chlorophenyl)-3-oxopropanenitrile, the main research area is amino diarylpyrimidin carbonitrile preparation adenosine receptor SAR docking.
Herein, document of a large collection of 108 2-amino-4,6-disubstituted-pyrimidine derivatives as potent, structurally simple, and highly selective A1AR ligands. The most attractive ligands were confirmed as antagonists of the canonical cyclic adenosine monophosphate pathway, and some pharmacokinetic parameters were preliminarilly evaluated. The library, built through a reliable and efficient three-component reaction, comprehensively explored the chem. space allowing the identification of the most prominent features of the structure-activity and structure-selectivity relationships around this scaffold. These included the influence on the selectivity profile of the aromatic residues at positions R4 and R6 of the pyrimidine core but most importantly the prominent role to the unprecedented A1AR selectivity profile exerted by the Me group introduced at the exocyclic amino group. The structure-activity relationship trends on both A1 and A2AARs were conveniently interpreted with rigorous free energy perturbation simulations, which started from the receptor-driven docking model that guided the design of these series.
Journal of Medicinal Chemistry published new progress about Adenosine A1 receptor antagonists. 21667-62-9 belongs to class nitriles-buliding-blocks, and the molecular formula is C9H6ClNO, Recommanded Product: 3-(3-Chlorophenyl)-3-oxopropanenitrile.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts