RESEARCH ARTICLE


Synthesis of Some 4,5-Dihydrothieno[3,2-e][1,2,4]Triazolo[4,3-a] Pyrimi-dine-2-Carboxamides as Anti-Inflammatory and Analgesic Agents



Omaima G. Shaaban1, Ola H. Rizk1, *, Aida E. Bayad2, Ibrahim M. El-Ashmawy3
1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt;
2 Univ. Fellow, Veterinary Services Unit, Faculty of Veterinary Medicine, University of Alexandria, Egypt;
3 Department of Veterinary Medicine, Faculty of Agricultural and Veterinary Medicine, Qassim University, Buraydah 1482, Al-Qassim, Saudi Arabia

Article Information


Identifiers and Pagination:

Year: 2013
Volume: 7
First Page: 49
Last Page: 65
Publisher ID: TOMCJ-7-49
DOI: 10.2174/1874104501307010049

Article History:

Received Date: 22/9/2013
Revision Received Date: 11/11/2013
Acceptance Date: 11/11/2013
Electronic publication date: 29/11/2013
Collection year: 2013

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Creative Commons License
© Shaaban et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt; Tel: +(203)4871317 ; Fax: + (203)4873273; Email: olarizk@yahoo.com


Abstract

A new series 4,5-dihydrothieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidine-2-carboxamide was synthesized. Twenty one newly synthesized compounds were investigated for their anti-inflammatory and analgesic activity using acute and subacute formalin-induced paw edema models and diclofenac Na as a reference. The acute toxicity (ALD50) and ulcerogenic effects of the active compounds were also determined. The thienotriazolopyrimidines 10a, 10c and 11c were found to exhibit remarkable anti-inflammatory activity at both models in addition to good analgesic activity with a delayed onset of action. Moreover, the active compounds showed high GI safety level and are well tolerated by experimental animals with high safety margin (ALD50 > 0.4 g/kg). Docking study using Molecular Operating Environment (MOE) version 2008.10 into COX-2 has been made for derivatives of highest anti-inflammatory activity.

Keywords: : Synthesis, thienotriazolopyrimidines, antiinflammatory activity, ulcerogenic effect, acute toxicity, analgesic activity, docking.