title: 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.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt;
authors.forename: Omaima G
authors.initials: OG
authors.lastname: Shaaban
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt;
authors.forename: Ola H
authors.initials: OH
authors.lastname: Rizk
authors.affiliation: Univ. Fellow, Veterinary Services Unit, Faculty of Veterinary Medicine, University of Alexandria, Egypt;
authors.forename: Aida E
authors.initials: AE
authors.lastname: Bayad
authors.affiliation: Department of Veterinary Medicine, Faculty of Agricultural and Veterinary Medicine, Qassim University, Buraydah 1482, Al-Qassim, Saudi Arabia.
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: El-Ashmawy
keywords: Synthesis; acute toxicity; analgesic activity; antiinflammatory activity; docking.; thienotriazolopyrimidines; ulcerogenic effect