STUDY OF ANTI-INFLAMMATORY AND ANTINOCICEPTIVE PROPERTIES OF NEW DERIVATIVES OF CONDENSED 3-AMINOTHIENO[2,3-b]PYRIDINES AND 1,4-DIHYDROPYRIDINES

Abstract

α-сyanothioacetamide derivatives are promising targets for the search for effective and safe antinociceptive agents with antipyretic and antiexudative activity. The aim. To conductin vivo experimentalstudy ofanti-inflammatory andanalgesic effects of new thienopyridines and 1,4-dihydropyridines derivatives. Materials and methods. The synthesized cyanothioacetamide derivatives were subjected to virtual bioscreening using Swiss Target Prediction online service. 140 laboratory rats were randomly distributed into intact and control (dextran edema) groups, reference groups (acetylsalicylic acid and nimesulide) and ten experimental groups for the investigated derivatives of thieno[2,3-b]pyridine and1,4-dihydropyridine. The anti-inflammatory activity ofthe compounds ata dose of5 mg/kg was evaluatedby modeling acute dextran edema ofrat paw. Determination of analgesic activity was carried out in the hotplate analgesic assay on 130 rats in comparison with sodium metamizole. Results. 1,4-dihydropyridines AZ331 and AZ420, as well as thienopyridine derivative AZ023 were determined to have strong anti-inflammatory activity (2.5 times more effective than nimesulide and2.2times more effective than acetylsalicylic acid). Compounds AZ023, AZ331 and AZ383 showed pronounced analgesic activity. The time of stay on the heated plate for rats of experimental groups that were fed withAZ331andAZ383for prophylactic purpose was respectively 9.56and9.93times more than the same index in the reference group. The animals receiving AZ023 were characterized by an increase in the latent reaction time up to 241.2 seconds, which is 14.53 times higher than that in the rats received sodium metamizole. Conclusion. New thienopyridineand1,4-dihydropyridinederivativeswithhighantiinflammatory andanalgesic activity were synthesizedandstudied; they were recognized as promising targets for further preclinical studies.