title: 4-(3-Methoxyphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones: new class of H1-antihistaminic agents.
abstract: A series of 1-substituted-4-(3-methoxyphenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones were synthesized by the cyclization of 2-hydrazino-3-(3-methoxyphenyl)-3H-quinazolin-4-one with various electrophile. The starting material 2-hydrazino-3-(3-methoxyphenyl)-3H-quinazolin-4-one was synthesized from 3-methoxy aniline by an innovative route. Title compounds were tested for their in vivo H1-antihistaminic activity on guinea pigs; all the tested compounds protected the animals from histamine induced bronchospasm significantly. Compound 1-methyl-4-(3-methoxyphenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (II) emerged as the most active compound of the series and was more potent (72.76%) than the reference standard chlorpheniramine maleate (71%). Compound II showed negligible sedation (10%) when compared to chlorpheniramine maleate (25%). Hence it could serve as prototype molecule for further development as a new class of H1-antihistaminic agents.
authors.affiliation: Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy, India. drvalagarsamy@gmail.com
authors.forename: V
authors.initials: V
authors.lastname: Alagarsamy
authors.forename: H K
authors.initials: HK
authors.lastname: Sharma
authors.forename: P
authors.initials: P
authors.lastname: Parthiban
authors.forename: J C Hanish
authors.initials: JC
authors.lastname: Singh
authors.forename: S Thirusenthil
authors.initials: ST
authors.lastname: Murugan
authors.forename: V Raja
authors.initials: VR
authors.lastname: Solomon
mesh_terms: D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D052999:Quinazolinones / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D014230:Triazoles / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D001993:Bronchodilator Agents; D002492:Central Nervous System Depressants; D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D007202:Indicators and Reagents; D052999:Quinazolinones; D014230:Triazoles