Vlasov S. Synthesis, physico-chemical and pharmacological properties of 6-substituted thieno[2,3-d]pyrimidines

The work is devoted to the development of the approaches and theoretical reasoning of the targeted search for the biologically active compounds among the derivatives of thieno[2,3-d]pyrimidine-6-caboxylic acids and 6-heteryl(acetyl)thieno[2,3-d]pyrimidines with various substituents at positions 1-4. The approaches for synthesis and modification of the compounds with oxo- and thio-groups at positions 2 and 4 of thieno[2,3-d]pyrimidine substituted at position 3, the substituted 6-acetylthieno[2,3-d]pyrimidines and 6-heterylthieno[2,3-d]pyrimidines with azole substituents were developed and improved. The relationship between structure and the antimicrobial activity of the obtained compounds has been analyzed. The prediction helped to identify the most probable pharmacological activity types; the screening experiments for anti-inflammatory, analgesic, histamine inhibition, anticancer activities together with the influence on the CNS and stomach mucosa were performed. The docking studies allowed development of the sustainable methodology for the search for the novel NSAIDs among the 6-substituted thieno[2,3-d]pyrimidines. The novel promising medicinal substance “Methyl 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate” with the high anti-inflammatory and analgesic activity has been proposed; the project the MCQ for this substance has been developed.