A series of pyridines and pyridine based sulfa-drugs as antimicrobial agents: Design, synthesis and antimicrobial activity

Resumo

Herein, we report a series of pyridines and their sulfa drug derivatives as antimicrobial agents. Regioselective alkylation followed by hydrozinolysis of 2-pyridone 1 gave the target compounds 2 and 3. Compound 3 was cyclized with acetylacetone or heated in dry benzene to give 2-(pyrazol-1-yl)nicotinonitrile 5 and 3-amino-1H-pyrazolo[3,4-b]pyridine derivatives 6, respectively. Diazotization of compound 3 with nitrous acid at low temperature afforded tetrazolo[1,5-a]pyridine derivative 8. Compounds 6 and 7 were obtained by condensation of hydrazine derivative 3 with D-glucose and D-ribose. Acid-mediated hydrolysis and sulfurization of dicyano compound 2 gave pyridine-3,5-dicarboxamide 11 and 2-thioxopyridine 12 derivatives, respectively. The later compound was alkylated with allyl bromide, benzyl chloride and mono chloroacetic acid to produce the corresponding S-alkylated derivatives 13–15. Compound 15 underwent the Thrope–Ziegler cyclization/condensation with sulfa-drugs to give the corresponding thienopyridine 16 and sulfonamide derivatives 17–19. Antimicrobial study of the new syntheized compounds demonstrated signficant activity of compounds 8–11 and 17–19.