Acta Pharm. 59 (2009) 97-106

full paper

Short communication

 

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

VEERACHAMY ALAGARSAMY, KUNCHU KAVITHA, MANI RUPESHKUMAR, VISWAS RAJA SOLOMON, JAYA KUMAR, DINAKARAN SATHESH KUMAR and HEMANT KUMAR SHARMA

drvalagarsamy@gmail.com

1 Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Fasalwadi, Sangareddy-502294, India

2 Bharathi College of Pharmacy, Bharathi Nagar, K. M. Doddi-571422, Mandya (Dist), India

3 Medicinal & Process Chemistry Division, Central Drug Research Institute, Lucknow-226001, India

4 Department of Pharmaceutical Chemistry, Nalanda College of Pharmacy Cheralpally, Nalgonda-508001, India

5 Department of Pharmaceutical Chemistry, Patel College of Pharmacy, Bhopal, India

Accepted January 15, 2009

 

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.

 

Keywords: quinazolin-5-ones, sedation, H1-antihistaminic agents