<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml">A series of novel 4-(3-ethylphenyl)-1-substituted-4<italic>H</italic>-[1,2,4] triazolo[4,3-<italic>a</italic>]quinazolin-5-ones (<bold>4a-j</bold>) were synthesized by the cyclization of 3-(3-ethylphenyl)-2-hydrazino-3<italic>H</italic>-quinazolin-4-one (<bold>3</bold>) with various one-carbon donors. The starting material, compound <bold>3</bold>, was synthesized from 3-ethyl aniline by a new innovative route with improved yield. When tested for their <italic>in vivo</italic> H1-antihistaminic activity on conscious guinea pigs, all test compounds protected the animals from histamine induced bronchospasm significantly. Compound 4-(3-ethylphenyl)-1-methyl-4<italic>H</italic> - [1,2,4]triazolo[4,3-<italic>a</italic>]quinazolin-5-one (<bold>4b</bold>) 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 <bold>4b</bold> 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.</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.

Synthesis and pharmacological investigation of novel 4-(3-ethylphenyl)-1-substituted-4<italic>H</italic>-[1,2,4]triazolo[4,3-<italic>a</italic>] quinazolin-5-ones as a new class of H1-antihistaminic agents

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

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

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

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

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

Acta Pharmaceutica

Synthesis and pharmacological investigation of novel 4-(3-ethylphenyl)-1-substituted-4-[1,2,4]triazolo[4,3-] quinazolin-5-ones as a new class of H-antihistaminic agents

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...

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

Publié en ligne: 20 mars 2009

Pages: 97 - 106

DOI: https://doi.org/10.2478/v10007-009-0003-1

Mots clés
kinazolin-5-oni, sedacija, H-antihistaminici

This content is open access.

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