Synthesis of biologically active N-methyl derivatives of amidines and cyclized five-membered products of amidines with oxalyl chloride

A series of substituted N-methylisonicotinamidine (2a–f), N-methylpyrazine-2-carboxamidine (2g–i) derivatives were synthesized by reaction of amidine derivatives (1a–i) with methyl iodide in presence of triethylamine. Five-membered condensed dihydroimidazolylbenzenesulfonamide derivatives (3a–i) were obtained by the reaction of amidine derivatives (1a–i) with acylating agent oxalyl chloride. All the compounds, i.e. 2a–i and 3a–i were purified by crystallization. Structures of all the synthesized compounds are supported by correct IR, 1H NMR, mass spectral and analytical data. Anti-inflammatory activity evaluation was carried out using carrageenan-induced paw oedema assay and compounds 2e, 3a and 3d exhibited good anti-inflammatory activity (44%, 31% and 37% activity at 50 mg/kg p.o., respectively). Analgesic activity evaluation was carried out using acetic acid writhing assay and compounds 2a and 3f gave 75% activity each at 100 mg/kg p.o.; on the other hand compounds 3a and 3d exhibited 60% analgesic activity each at 50 mg/kg p.o. Compounds 3a and 3d exhibited good anti-inflammatory and analgesic activities.

Graphical abstractA number of N-methylisonicotinamidine (2a–f), N-methylpyrazine-2-carboxamidine (2g–i) and dihydroimidazolylbenzenesulfonamide (3a–i) derivatives have been synthesized and screened for anti-inflammatory and analgesic activities. Compounds 3a and 3d exhibited good anti-inflammatory and analgesic activities.Figure optionsDownload full-size imageDownload as PowerPoint slide