Synthesis and pharmacological investigation of novel 4-(3-ethylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a] quinazolin-5-ones as a new class of H1-antihistaminic agents.

A series of novel 4-(3-ethylphenyl)-1-substituted-4H-[1,2,4] triazolo[4,3-a]quinazolin-5-ones (4a-j) were synthesized by the cyclization of 3-(3-ethylphenyl)-2-hydrazino-3H-quinazolin-4-one (3) with various one-carbon donors. The starting material, compound 3, was synthesized from 3-ethyl aniline by a new innovative route with improved yield. When tested for their in vivo H1-antihistaminic activity on conscious guinea pigs, all test compounds protected the animals from histamine induced bronchospasm significantly. Compound 4-(3-ethylphenyl)-1-methyl-4H - [1,2,4]triazolo[4,3-a]quinazolin-5-one (4b) emerged as the most active compound of the series and it is more potent (74.6 % protection) compared to the reference standard chlorpheniramine maleate (71 % protection). Compound 4b shows negligible sedation (10 %) compared to chlorpheniramine maleate (30 %). Therefore compound 4b can serve as the leading compound for further development of a new class of H1-antihistamines.