title: Synthesis and pharmacological investigation of novel 4-(2-methylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H(1)-antihistaminic agents.
abstract: A series of novel 1-substituted-4-(2-methylphenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones were synthesized by the cyclization of 2-hydrazino-3-(2-methylphenyl)-3H-quinazolin-4-one with various one carbon donors. The starting material 2-hydrazino-3-(2-methylphenyl)-3H-quinazolin-4-one was synthesized from 2-methyl aniline by a novel innovative route. The title compounds were tested for their in vivo H(1)-antihistaminic activity on guinea pigs; all the tested compounds protected the animals from histamine-induced bronchospasm significantly. Compound 1-methyl-4-(2-methylphenyl)-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 (72.45%) when compared to the reference standard chlorpheniramine maleate (71%). Compound II showed negligible sedation (11%) when compared to chlorpheniramine maleate (30%). Hence it could serve as the prototype molecule for further development as a new class of H(1)-antihistaminic agents.
authors.affiliation: Medicinal Chemistry Research Laboratory, Dayananda Sagar College of Pharmacy, Kumaraswamy Layout, Bangalore 560 078, India. samy_veera@yahoo.com
authors.forename: V
authors.initials: V
authors.lastname: Alagarsamy
authors.forename: M
authors.initials: M
authors.lastname: Rupeshkumar
authors.forename: K
authors.initials: K
authors.lastname: Kavitha
authors.forename: S
authors.initials: S
authors.lastname: Meena
authors.forename: D
authors.initials: D
authors.lastname: Shankar
authors.forename: A A
authors.initials: AA
authors.lastname: Siddiqui
authors.forename: R
authors.initials: R
authors.lastname: Rajesh
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D008297:Male; D008745:Methylation; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*
chemical_list: D006634:Histamine H1 Antagonists; D011799:Quinazolines; D014230:Triazoles