Synthesis and pharmacological investigation of novel 4-(2-methylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H(1)-antihistaminic agents.

Research paper by V V Alagarsamy, M M Rupeshkumar, K K Kavitha, S S Meena, D D Shankar, A A AA Siddiqui, R R Rajesh

Indexed on: 23 Nov '07Published on: 23 Nov '07Published in: European Journal of Medicinal Chemistry


A series of novel 1-substituted-4-(2-methylphenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones were synthesized by the cyclization of 2-hydrazino-3-(2-methylphenyl)-3H-quinazolin-4-one with various one carbon donors. The starting material 2-hydrazino-3-(2-methylphenyl)-3H-quinazolin-4-one was synthesized from 2-methyl aniline by a novel innovative route. The title compounds were tested for their in vivo H(1)-antihistaminic activity on guinea pigs; all the tested compounds protected the animals from histamine-induced bronchospasm significantly. Compound 1-methyl-4-(2-methylphenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (II) emerged as the most active compound of the series and it is more potent (72.45%) when compared to the reference standard chlorpheniramine maleate (71%). Compound II showed negligible sedation (11%) when compared to chlorpheniramine maleate (30%). Hence it could serve as the prototype molecule for further development as a new class of H(1)-antihistaminic agents.