Mallo-Abreu, Ana; Prieto-Diaz, Ruben; Jespers, Willem; Azuaje, Jhonny; Majellaro, Maria; Velando, Carmen; Garcia-Mera, Xerardo; Caamano, Olga; Brea, Jose; Loza, Maria I.; Gutierrez-de-Teran, Hugo; Sotelo, Eddy published the artcile< A Nitrogen-Walk Approach to Explore Bioisosteric Replacements in a Series of Potent A2B Adenosine Receptor Antagonists>, Computed Properties of 1003-32-3, the main research area is dihydrobenzoimidazopyrimidine carboxylate preparation SAR docking A2B adenosine receptor antagonist.
A systematic exploration of bioisosteric replacements for furan and thiophene cores in a series of potent A2BAR antagonists was carried out using the nitrogen-walk approach. A collection of 42 novel alkyl 4-substituted-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates I [R = H, cyclopentyl, Ph, etc.; R1 = Et, i-Pr], which contain 18 different pentagonal heterocyclic frameworks at position 4, was synthesized and evaluated. This study enabled the identication of new ligands that combine remarkable affinity (Ki < 30 nM) and exquisite selectivity. The SAR trends identified were substantiated by a mol. modeling study, based on a receptor-driven docking model and including a systematic free energy perturbation (FEP) study. Preliminary evaluation of the CYP3A4 and CYP2D6 inhibitory activity in optimized ligands evidenced weak and negligible activity resp. The stereospecific interaction between hA2BAR and the eutomer of the most attractive novel antagonist (S)-II (Ki = 3.66 nM) was validated. Journal of Medicinal Chemistry published new progress about Adenosine A2B receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Computed Properties of 1003-32-3.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica