Synthesis and pharmacological investigation of novel 4-benzyl-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H1-antihistaminic agents.
A series of novel 1-substituted-4-benzyl-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones were synthesized by the cyclization of 2-hydrazino-3-benzyl-3H-quinazolin-4-one with various one-carbon donors. The starting material 2-hydrazino-3-benzyl-3H-quinazolin-4-one was synthesized from benzylamine by a new innovative route. When tested for their in vivo H1 -antihistaminic activity on guinea pigs, all the test compounds protected the animals from histamine induced bronchospasm significantly. The compound 1-methyl-4-benzyl-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 (percent protection 76%) when compared to the reference standard chlorpheniramine maleate (percent protection 71%). Compound II showed negligible sedation (7%) when compared to chlorpheniramine maleate (30%). Hence it could serve as prototype molecule for further development as a new class of H1 -antihistamines.
Alagarsamy
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Medicinal Chemistry Research Laboratory, Dayananda Sagar College of Pharmacy, Kumaraswamy Layout, Bangalore 560 078, India. samy_veera@yahoo.com
Solomon
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VR
Murugan
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M
D000818:Animals; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared
D006634:Histamine H1 Antagonists; D011799:Quinazolines