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

Abstract

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.