title: 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.
abstract: 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.
authors.affiliation: Medicinal Chemistry Research Laboratory, Arulmigu Kalasalingam College of Pharmacy, Anand Nagar, Krishnan koil-626 190, India. samy_veera@yahoo.com
authors.forename: V
authors.initials: V
authors.lastname: Alagarsamy
authors.forename: Rajani
authors.initials: R
authors.lastname: Giridhar
authors.forename: M R
authors.initials: MR
authors.lastname: Yadav
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D001986:Bronchial Spasm / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D006168:Guinea Pigs; D039563:Histamine H1 Antagonists, Non-Sedating / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism; D012890:Sleep / Q000187:drug effects; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: C515702:1-methyl-4-(4-chloro phenyl)-4H-(1,2,4)triazolo(4,3-a)quinazolin-5-one; C515703:1-methyl-4-(4-methoxy phenyl)-4H-(1,2,4)triazolo(4,3-a)quinazolin-5-one; D039563:Histamine H1 Antagonists, Non-Sedating; D011799:Quinazolines; D011969:Receptors, Histamine H1; D014230:Triazoles