Synthesis of 2-chloropurine ribosides with chiral amino acid amides at C6 and their evaluation as A < sub > 1 < /sub > adenosine receptor agonists

Bioorg Chem. 2022 May 18;126:105878. doi: 10.1016/j.bioorg.2022.105878. Online ahead of print.ABSTRACTA series of purine ribonucleosides bearing chiral amino acid amides at the C6 position of 2-chloropurine was synthesized. Molecular docking of the synthesized analogs of 2-chloroadenosine by their affinity for A1 adenosine receptors (A1ARs) was conducted. The investigation of A1AR stimulating activity of synthesized nucleosides was carried out in a model of an isolated mouse atrium. We have shown that derivatives with tyrosine, valine, and serine residues exhibit the properties of A1AR partial agonists. Animal experiments in the open field test have shown that these compounds have different profiles of psychoactive action. These nucleosides have an ophthalmic hypotensive effect and reduce intraocular pressure in a manner slightly inferior to that of timolol and brimonidine. The synthesized nucleosides can be the basis for further design and synthesis of new A1AR agonists.PMID:35660725 | DOI:10.1016/j.bioorg.2022.105878

Source: Bioorganic Chemistry - June 6, 2022 Category: Chemistry Authors: Maria Ya Berzina Barbara Z Eletskaya Alexei L Kayushin Elena V Dorofeeva Olga I Lutonina Ilya V Fateev Alexander S Paramonov Maria A Kostromina Evgeniy A Zayats Yulia A Abramchik Dmitriy V Maltsev Ludmila V Naumenko Alena S Taran Dmitry S Yakovlev Alexand Source Type: research