《Substituted 4-phenylthiazoles: Development of potent and selective A1, A3 and dual A1/A3 adenosine receptor antagonists》 was published in European Journal of Medicinal Chemistry in 2020. These research results belong to Abdelrahman, Aliaa; Yerande, Swapnil G.; Namasivayam, Vigneshwaran; Klapschinski, Tim A.; Alnouri, Mohamad Wessam; El-Tayeb, Ali; Mueller, Christa E.. Category: pyridine-derivatives The article mentions the following:
Adenosine acts as a powerful signaling mol. via four distinct G protein-coupled receptors, designated A1, A2A, A2B and A3 adenosine receptors (ARs). A2A and A2B ARs are Gs-coupled, while A1 and A3 ARs inhibit cAMP production via Gi proteins. Antagonists for A1 and A3 ARs may be useful for the treatment of (neuro)inflammatory diseases including acute kidney injury and kidney failure, pulmonary diseases, and Alzheimer’s disease. In the present study, we optimized the versatile 2-amino-4-phenylthiazole scaffold by introducing substituents at N2 and C5 to obtain A1 and A3 AR antagonists including dual-target compounds Selective A1 antagonists with (sub)nanomolar potency were produced, e.g. 11 and 13. These compounds showed species differences being significantly more potent at the rat as compared to the human A1 AR, and were characterized as inverse agonists. Several potent and selective A3 AR antagonists, e.g. 7, 8, 17 and 22 (Ki values of 5-9 nM at the human A3 AR) were prepared, which were much less potent at the rat orthologue. Moreover, dual A1/A3 antagonists (10, 18) were developed showing Ki values between 8 and 42 nM. Docking and mol. dynamic simulation studies using the crystal structure of the A1 AR and a homol. model of the A3 AR were performed to rationalize the observed structure-activity relationships. The experimental part of the paper was very detailed, including the reaction process of 2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8Category: pyridine-derivatives)
2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8) belongs to pyridine. Pyridine is widely used in the precursor to agrochemicals and pharmaceuticals. Also, it is used as an important reagent and organic solvent.Category: pyridine-derivatives