Synthesis and Biological Evaluation of Some Novel Thieno[2,3-d] pyrimidine Derivatives as Potential Anti-inflammatory and Analgesic Agents

Alaa   A.   El-Tombary; Soad   A.M.   El-Hawash; Nargues   S.   Habib; Raafat      Soliman; Ibrahim   M.   El-Ashmawy; Omaima   G.   Shaaban

doi:10.2174/1573406411309080012

Abstract

A novel series of thienopyrimidine derivatives bearing various substituents or linked to various heterocyclic moieties through atoms spacers were prepared starting from 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6- carboxamide potassium salt 3. Twelve out of the prepared compounds were selected and evaluated for their antiinflammatory activity using the formalin-induced paw edema and the turpentine oil-induced granuloma pouch bioassays using diclofenac sodium as a reference standard. The ulcerogenic effects and acute toxicity (ALD₅₀) values of these compounds were also determined. In addition, the analgesic activity of the same compounds was evaluated using the rat tail withdrawal technique. The results revealed that compounds 5a, 13, 14b, 15a, 16a and 16b had high anti-inflammatory effect comparable to diclofenac sodium, whereas compounds 5a, 14a, 15a and 16a revealed pronounced analgesic activity that is equal or higher than that of the reference. All of the tested compounds revealed high GI safety profile and were well tolerated by the experimental animals with high safety margin (ALD₅₀ > 3.0g/Kg).

Keywords: Thienopyrimidine, pyrazole, dihydropyrazolone, thiazolidine, oxadiazole, thiadiazole, anti-inflammatory, analgesic, ulcerogenic effect.