Synthesis and pharmacological investigation of novel 1‐substituted‐4‐(4‐substituted phenyl)‐4H‐[1,2,4]triazolo[4,3‐a]quinazolin‐5‐ones as a new class of H1‐antihistamine agents

A series of novel 1‐substituted‐4‐(4‐substituted phenyl)‐4H‐[1,2,4]triazolo[4,3‐a]quinazolin‐5‐ones was synthesized by the cyclization of 2‐hydrazino‐3‐(4‐substituted phenyl)‐3H‐quinazolin‐4‐one with various one‐carbon donors. The starting material, 2‐hydrazino‐3‐(4‐substituted phenyl)‐3H‐quinazolin‐4‐one, was synthesized from 4‐substituted aniline by a novel innovative route. When tested for in‐vivo H1‐antihistamine activity on conscious guinea‐pigs, all the test compounds significantly protected the animals against histamine‐induced bronchospasm. The compound 1‐methyl‐4‐(4‐chloro phenyl)‐4H‐[1,2,4]triazolo[4,3‐a]quinazolin‐5‐one (VII) was more potent (72.71% protection), and 1‐methyl‐4‐(4‐methoxy phenyl)‐4H‐[1,2,4]triazolo[4,3‐a]quinazolin‐5‐one (II) was equipotent (71% protection), when compared with the reference standard, chlorpheniramine maleate (71% protection). Compounds II and VII showed negligible sedation (5% and 8% respectively) when compared with chlorpheniramine maleate (25%). Compounds II and VII could serve as prototype molecules for further development as a new class of H1‐antihistamines.