The synthesis and biological assessment of [[1,2,4]triazolo[4,3-a]pyridine-3-yl]acetamides with an 1,2,4-oxadiazol cycle in positions 6, 7 and 8

• Published in: Z͡h︡urnal orhanichnoï ta farmat͡s︡evtychnoï khimiï Vol. 17; no. 1(65); pp. 28 - 35
• Main Authors: Karpina, V. R., Kovalenko, S. S., Kovalenko, S. M., Zaremba, O. V., Silin, O. V., Langer, T.
• Format: Journal Article
• Language: English
• Published: National University of Pharmacy (Kharkiv) 13.03.2019
• Subjects: oxadiazole; triazolopyridine
• ISSN: 2308-8303; 2518-1548
• DOI: 10.24959/ophcj.19.965

Fused heterocyclic 1,2,4-triazoles have provided much attention due to variety of their interesting biological properties. Aim. To develop the method for the synthesis of novel 2-[(1,2,4-oxadiazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl]acetamides and conduct the biological assessment of the compounds synthesized. Results and discussion. A diverse set of acetamides newly synthesized consists of 32 analogs bearing an 1,2,4-oxadiazole cycle in positions 6, 7 and 8. A convenient scheme of the synthesis starts from commercially available 2-chloropyridine-3-, 2-chloropyridine-4-, 2-chloropyridine-5-carboxylic acids with amidoximes to form the corresponding 2-chloro-[3-R1-1,2,4-oxadiazol-5-yl]pyridines, then follows the reaction of hydrazinolysis with an excess of hydrazine hydrate. The process continues via the ester formation with the pyridine ring closure, then the amide formations of the end products are obtained by hydrolysis into acetic acid. Experimental part. A series of new 2-[6-(1,2,4-oxadiazol-5-yl)-, 2-[7-(1,2,4-oxadiazol-5-yl)-, 2-[8-(1,2,4-oxadiazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl]acetamides were obtained in good yields, and their structures were proven by the method of 1H NMR spectroscopy. The prognosis and study of their pharmacological activity were also conducted. Conclusions. The synthetic approach of obtaining the representatives of 2-[(1,2,4-oxadiazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl]acetamides previously unknown can be used as an applicable method for the synthesis of diverse functionalized [1,2,4]triazolo[4,3-a]pyridine derivatives.