Synthesis and pharmacological profile of some new 2-substituted-2, 3-dihydro-1H-perimidine

摘要

Background and objective: The development of new antimicrobial drugs is stilldemanded as there is increasing resistance of microorganisms to currently availableantimicrobial drugs and searches for safer nonsteroidal anti-inflammatory agents withgreater cyclooxygenase COX II selectivity is challenging. The new series of 2-substituted2,3-dihydro-1H-perimidine(4a-j) that are close analogs to Naproxen 5, might inhibit COX IIenzyme in a similar manner to naproxen 5. This study aimed to synthesize some newheterocyclic compounds for enhancing biological activity.Methods: 1,8-Diaminonaphthalene 2 was condensed with a variety of aldehydes andketones 3 to afford a new series of 2-substituted-2,3-dihydro-1H-perimidines4a-j usinga suitable synthetic strategy. All the synthesized 2,3-dihydro-1H-perimidine compounds4a-jwere screened for their invitro antimicrobial activities against two identifiable strainsusing the agar diffusion method. At the same time, the synthesized pyrimidine derivatives4a-were evaluated for their COX inhibition activity. Supplementary to these, theconstitutions of the newly synthesized 2,3-dihydro-1H-perimidines 4a-j had been confirmedon the basis of their IR, 1H- and 13C-NMR spectral data.Results: The synthesized 2-substituted-2,3-dihydro-1H-perimidine compounds 4a-jexhibited promising antibacterial activity against Escherichia coli microorganism,while none of the synthesized derivatives 4a-jshowed likely result against Staphylococcusaureus strain. In addition, compound 4b had the most potent anti-inflammatory activity withan inhibition rate of 47% at 1000 nM.Conclusion: The synthesized products4a-j possessed antibacterial activity (towardsEscherichia coli microorganism; however, compounds 4c,4e, and 4j took the highestactivity) and anti-inflammatory activity (compound 4b showed the highest inhibition rate).