Synthesis of 1-Substituted-4-(Pyridin-4-yl) [1,2,4] Triazolo [4,3-a] Quinazolin-5(4H)-ones as a New Class of H1- Antihistaminic Agents

Abstract

Purpose: To synthesize a new series of 1-substituted-4-(pyridin-4-yl) [1,2,4] triazolo [4,3-a]quinazolin- 5(4H)-ones and evaluate them for H1-antihistaminic activity with negligible side effects in guinea pigs.
Methods: The synthesized compounds were characterized by Infrared spectroscopy (IR), proton nuclear magnetic resonance (¹H-NMR) and mass spectrometry (MS) data. The purity of the compounds was determined by elemental analysis. The antihistaminic activity of the compounds was evaluated in guinea pigs by histamine-induced bronchoconstriction method.
Results: Among the series, 1-methyl-4-(pyridin-4-yl) [1,2,4] triazolo [4,3-a] quinazolin-5(4H)-one (S5) was the most potent with 72.85 % protection and its potency was comparable to that of the reference, chlorpheniramine maleate (70.09 %). Interestingly, the sedative property of compound S5 was negligible (5.09 %) when compared to chlorpheniramine maleate (29.58 %).
Conclusion: Compound S5 can serve as a lead molecule for further development into a new class of H1-antihistaminic agents.

Keywords: Quinazolin-5-ones, Antihistaminic activity, Histamine, Bronchoconstriction