Synthesis of 4-butyl-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H(1)-antihistaminic agents.
A series of novel 4-butyl-1-substituted-4H-[1,2,4]triazolo [4,3-a] quinazolin-5-ones were synthesized by the cyclization of 3-butyl-2-hydrazino-3H-quinazolin-4-one with various one carbon donors. The starting material 3-butyl-2-hydrazino-3H-quinazolin-4-one was synthesized from butyl amine by a new innovative route. When tested for their in vivo H(1)-antihistaminic activity on conscious guinea pigs, all the test compounds protected the animals from histamine induced bronchospasm significantly. Compound 4-butyl-1-methyl-4H-[1,2,4]triazolo[4,3-a] quinazolin-5-one (II) emerged as the most active compound of the series and it is equipotent (71.91% protection) when compared to the reference standard chlorpheniramine maleate (71% protection). Compound II show negligible sedation (9%) when compared to chlorpheniramine maleate (30%).
Alagarsamy
V
V
Dayananda Sagar College of Pharmacy, Kumaraswamy Layout, Bangalore 560 078, India. drvalagarsamy@gmail.com
Shankar
D
D
Murugesan
S
S
D000465:Algorithms; D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced / Q000517:prevention & control; D002744:Chlorpheniramine / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D011799:Quinazolines; D002744:Chlorpheniramine; D006632:Histamine