Design,Synthesis And Biological Evaluations Of Thienopyrimidine Diones

Neurodegenerative diseases have become an important factor affecting our life and health.Because of their complex pathogenesis,Neurodegenerative diseases are hard to cure.It has been reported that the activation of the CB2 receptor in the microglia can inhibit excessive activation and inflammation.Therefore,CB2 receptor has been identified as a new target for the study of neuroprotective drugs.Thus,our research has very practical significance.In this paper,the design based on the preliminary research and the conception of bio-isosterism.Herein,19 novel compounds have been synthesized and structurally characterized by 1H NMR.The purity of these compounds were tested by high performance liquid chromatography.The test showed the compounds A12,A15,A18 exhibit higher affinity and potency for CB2 receptor than the compound CP55940 during in vitro study.Among them,EC50 value of compound A12 was 19.5 nM.Moreover,We found that the functionality of these ligands is controlled by the position of substituents on the thiophene ring.