title: Synthesis and pharmacological investigation of novel 4-(3-ethylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a] quinazolin-5-ones as a new class of H1-antihistaminic agents.
abstract: A series of novel 4-(3-ethylphenyl)-1-substituted-4H-[1,2,4] triazolo[4,3-a]quinazolin-5-ones (4a-j) were synthesized by the cyclization of 3-(3-ethylphenyl)-2-hydrazino-3H-quinazolin-4-one (3) with various one-carbon donors. The starting material, compound 3, was synthesized from 3-ethyl aniline by a new innovative route with improved yield. When tested for their in vivo H1-antihistaminic activity on conscious guinea pigs, all test compounds protected the animals from histamine induced bronchospasm significantly. Compound 4-(3-ethylphenyl)-1-methyl-4H - [1,2,4]triazolo[4,3-a]quinazolin-5-one (4b) emerged as the most active compound of the series and it is more potent (74.6 % protection) compared to the reference standard chlorpheniramine maleate (71 % protection). Compound 4b shows negligible sedation (10 %) compared to chlorpheniramine maleate (30 %). Therefore compound 4b can serve as the leading compound for further development of a new class of H1-antihistamines.
authors.affiliation: Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Fasalwadi, Sangareddy-502294, India. drvalagarsamy@gmail.com
authors.forename: Veerachamy
authors.initials: V
authors.lastname: Alagarsamy
authors.forename: Kunchu
authors.initials: K
authors.lastname: Kavitha
authors.forename: Mani
authors.initials: M
authors.lastname: Rupeshkumar
authors.forename: Viswas Raja
authors.initials: VR
authors.lastname: Solomon
authors.forename: Jaya
authors.initials: J
authors.lastname: Kumar
authors.forename: Dinakaran Sathesh
authors.initials: DS
authors.lastname: Kumar
authors.forename: Hemant Kumar
authors.initials: HK
authors.lastname: Sharma
mesh_terms: D000818:Animals; D001986:Bronchial Spasm / Q000209:etiology / Q000517:prevention & control*; D002744:Chlorpheniramine / Q000009:adverse effects / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011799:Quinazolines / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D006634:Histamine H1 Antagonists; D011799:Quinazolines; D002744:Chlorpheniramine; D006632:Histamine