Abstract:
Current methods for synthesis of oxazolo[5,4-b]- and oxazolo[4,5-b]pyridines have several limitations, such
as severe reaction conditions, lengthy reaction times, low yields and concurrent formation of side reaction
products. This article presents the results of study focused on a one-step method for the synthesis of new derivatives
of oxazolo[5,4-b]pyridine incorporating an aliphatic carboxylic group as a linker. During the investigation
of acylation reactions of 3-aminopyridine-2(1H)-ones with cyclic anhydrides of dicarboxylic acids
(succinic, maleic and glutaric), it was found that the monoamides formed at the initial stage undergo intramolecular
cyclization yielding derivatives of oxazolo[5,4-b]pyridine. Subsequently, the reaction conditions were
studied and optimized to achieve the target compounds with high yield and purity. The potential antiinflammatory
activity of the obtained derivatives of oxazolo[5,4-b]pyridine was evaluated by molecular docking
method using AutoDock Vina software. Compounds 11-14b exhibited higher binding affinity with the selected
target protein Prostaglandin synthase-2 (1CX2) compared to the reference anti-inflammatory drug diclofenac.
Thus, taking into account the results of in silico analyses, the newly synthesized oxazolo[5,4-
b]pyridine derivatives based on 3-aminopyridine-2(1H)-ones are promising candidates for further investigation
of their potential anti-inflammatory activity through in vivo methods.
