Structure-kinetics relationships of Capadenoson derivatives as adenosine A 1 receptor agonists

Simulation and Comparative Analysis of Different Binding Modes of Non‐nucleoside Agonists at the A2AAdenosine Receptor

“…The first binding mode (binding mode 1, Figure A) presents the compounds oriented in a similar way to the one previously described for analogue agonists at the ARs ,,,. In detail, the 5‐cyano group and the 6‐amine of the pyridine derivatives (or the 4‐amine and the 5‐cyano group of the pyrimidines) point toward the amide function of Asn253 6.55 giving a polar interaction with this residue.…”

“…On the contrary, experimental data describing the binding mode of non‐nucleoside agonists at the ARs are still lacking and mutagenesis studies reported in literature showed that the ligand‐receptor recognition patterns could be slightly different for nucleoside and non‐nucleoside derivatives . Some molecular modelling studies attempted to predict the interaction between ARs and specific non‐nucleoside agonists, leading to the sketch of different arrangements of the ligands within the binding cavity ,,. The understanding of the binding mode of these molecules at the AR cavities could significantly help the design of novel agonists based on a simplified non‐nucleoside structure, with advantages considering an easier synthetic route or the possibility to explore different scaffolds and various substituents.…”

Non-Nucleoside Agonists of the Adenosine Receptors: An Overview

“…A biased agonism of Capadenoson was also assessed since this compound exhibited high potency in the activation of all the intracellular pathways upon A 1 AR stimulation, with the exception of the intracellular calcium mobilization, where the effect was lower with respect to other A 1 AR reference agonists [49]. Considering the AR affinity, Capadenoson showed also a high A 1 AR selectivity versus the other AR subtypes where the percentage of radioligand displacement was 0-2.5% [36]. In contrast, a recent work reported that this molecule can also bind the A 2B AR with a Ki of about 300 nM, but the authors did not specify the affinity at the other subtypes.…”

“…The early data are related to non-selective agonists ranging from partial to full agonist profiles. Subsequent reports described further non-nucleoside derivatives endowed with low nanomolar potency and improved selectivity for the A 1 , A 2A , or A 2B AR subtypes [30][31][32][33][34][35][36][37][38]. Structural features and biological activity of these molecules, synthetic approaches, and molecular modelling studies simulating the interaction between these compounds and AR targets are reviewed in this work.…”

Lithiation of 2-bromo-4-(1,3-dioxolan-2-yl)-1,3-thiazole

“…1,3-Thiazole derivatives exhibit the activities of selective enzyme inhibitors, [1][2][3][4] sigma receptors, 5,6 adenosine receptors 7,8 antagonists, and new T-type calcium channel blockers. 9 The actual task today is to obtain polyfunctional 1,3-thiazoles, which are suitable for further modification in order to synthesize the libraries of thiazole derivatives for screening and searching for pharmacologically promising compounds.…”