Synthesis and pharmacological investigation of novel 1-substituted-4-phenyl-1,2,4-triazolo[4,3-a]quinazolin-5(4H)-ones as a new class of H1-antihistaminic agents.
A series of novel 1-substituted-4-phenyl-1,2,4-triazolo[4,3-a]quinazolin-5(4H)-ones 7 were synthesized by the cyclization of 2-hydrazino-3-phenylquinazolin-4(3H)-one 6 with various one carbon donors. The starting material 2-hydrazino-3-phenylquinazolin-4(3H)-one 6, was synthesized from aniline 1 by a novel innovative route. When tested for their in vivo H(1)-antihistaminic activity on conscious guinea pigs all the test compounds protected the animals from histamine induced bronchospasm significantly, whereas the compound 1-methyl-4-phenyl-1,2,4-triazolo[4,3-a]quinazolin-5(4H)-one 7b (percentage protection 70.7%) was found to be equipotent with the reference standard chlorpheniramine maleate (percentage protection 71%). These compounds show negligible sedation ( approximately 5%) when compared to the reference standard (26%). Hence they could serve as prototype molecules for future development.
Alagarsamy
Veerachamy
V
Medicinal Chemistry Laboratory, Periyar College of Pharmaceutical Sciences for Girls, Trichy 620 021, Tamilnadu, India. samy_veera@yahoo.com
Giridhar
Rajani
R
Yadav
Mangae Ram
MR
Yadav
Mangai Ram
MR
D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced / Q000517:prevention & control; D002744:Chlorpheniramine / Q000494:pharmacology; D003500:Cyclization; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis* / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D011799:Quinazolines; D014230:Triazoles; D002744:Chlorpheniramine