Synthesis and pharmacological investigation of novel 1-alkyl-4-(4-substituted aryl/heteroaryl)-1,2,4-triazolo [4,3- a] quinazolin-5 (4H)-ones as a new class of H1-antihistaminic agents.
A series of novel 1-alkyl-4-(4-substituted aryl/heteroaryl)- 1,2,4-triazolo [4,3-a] quinazolin-5(4H)-ones were synthesized by the cyclization of 2-hydrazino-3-(4-subst. aryl/heteroaryl) quinazolin-4(3H)-one with various carbon donors. The starting material, 2-hydrazino-3-(4-subst. aryl/heteroaryl) quinazolin-4(3H)-one, was synthesized from 4-subst. arylamine/ heteroarylamine by a novel innovative route. When tested for their in vivo Hi-antihistaminic activity on conscious guinea pigs, all the test compounds protected the animals from histamine induced bronchospasm significantly, whereby the compound 1-methyl-4-(2-py-ridyl)-1,2,4-triazolo[4,3-a] quinazolin-5(4H)-one (II) was found to be more potent (percent protection 71.43 %) when compared to the reference standard, chlorpheniramine maleate (percent protection 71 %). Compound II showed negligible sedation (8 %) when compared to chlorpheniramine maleate (25 %). Hence it could serve as prototype molecule for further development as a new class of H1-antihistamines.
Alagarsamy
Veerachamy
V
Medicinal Chemistry Research Laboratory, Arulmigu Kalasalingam College of Pharmacy, Anand Nagar, Krishnan koil-626 190, Tamilnadu State, India. samy_veera@yahoo.com
Yadav
Mangae Ram
MR
Giridhar
Rajani
R
D000818:Animals; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D006993:Hypnotics and Sedatives; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008970:Molecular Weight; D009043:Motor Activity / Q000187:drug effects; D052999:Quinazolinones / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D014230:Triazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D007202:Indicators and Reagents; D052999:Quinazolinones; D014230:Triazoles