Synthesis, Anti-Inflammatory, Analgaesic and Anti-Amoebic Activity Evaluation of Some Pyrimidobenzimidazole and Pyrimidopyridoimidazole Derivatives

Abstract

o-Phenylenediamine, 4-nitro-1,2-phenylenediamine, 3,4-diaminobenzophenone, 3,4-diaminotoluene, 4,5-dimethylphenylenediamine and 3,4-diaminobenzoic acid (1a–f) react with 4-isothiocyanatobutan-2-one to give the pyrimidobenzimidazole derivatives (2a–f) respectively. Condensation of 4-nitro-1,2-phenylenediamine with 4-isothiocyanatobutan-2-one at room temperature gave the thiourea derivative (3). o-Nitroaniline, on condensation with 4-isothiocyanatobutan-2-one at pH ca. 5 and under reflux conditions, gave the thiourea derivative (4). 2,3-Diaminopyridine, on condensation with 4-isothiocyanatobutan-2-one, gave product (5). Condensation of 2,3-diaminopyridine with 4-isothiocyanato-4-methylpentan-2-one using acetic acid as solvent gave compounds (6)–(8), whereas compounds (7) and (9) were isolated from the same reagents in dimethylformamide (DMF). 4-Isothiocyanato-4-methylpentan-2-one, on refluxing in acetic acid, gave compound (6). Anti-inflammatory activity evaluation was carried out at 100 mg/kg p.o. (paw oedema) for compounds (2a–f), (7) and (8). Compounds (2b), (2d) and (7) showed good anti-inflammatory and analgesic activities. Anti-amoebic activity evaluation of (2a–f) and (7) against Entamoeba histolytica (strain HM-1: IMSS) was carried out, and compound (2b) exhibited anti-amoebic activity similar to metronidazole in vitro.