Acta Pharmaceutica, Vol. 59 No. 1, 2009.
Short communication, Note
https://doi.org/10.2478/v10007-009-0003-1
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
; Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Fasalwadi, Sangareddy-502294, India
KUNCHU KAVITHA
; Bharathi College of Pharmacy, Bharathi Nagar, K. M. Doddi-571422, Mandya (Dist), India
MANI RUPESHKUMAR
; Bharathi College of Pharmacy, Bharathi Nagar, K. M. Doddi-571422, Mandya (Dist), India
VISWAS RAJA SOLOMON
; Medicinal & Process Chemistry Division, Central Drug Research Institute, Lucknow-226001, India
JAYA KUMAR
; Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Fasalwadi, Sangareddy-502294, India
DINAKARAN SATHESH KUMAR
; Department of Pharmaceutical Chemistry, Nalanda College of Pharmacy Cheralpally, Nalgonda-508001, India
HEMANT KUMAR SHARMA
; Department of Pharmaceutical Chemistry, Patel College of Pharmacy, Bhopal, India
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.
Keywords
quinazolin-5-ones; sedation; H1-antihistaminic agents
Hrčak ID:
31554
URI
Publication date:
1.3.2009.
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