Design,Synthesis,and Activity Study Of Indole Ketones,Anthraquinones

Part 1.Design,synthesis and activity study of indole ketonesProtease-activated receptors(PARs)is a kind of GPCR on the cell surface.Almost all cells in the human body have the existence and expression of different types of PARS,and their physiological functions is very extensive.Protease-activated receptors currently have four family members: PAR1,PAR2,PAR3,and PAR4.In addition to PAR2 is a pancreatic receptor,the others is thrombin receptors.The expression of human platelets in PAR1 and PAR4 is an important target for antithrombotic drugs.Because of PAR1 have a higher affinity for thrombin than PAR4,the PAR1 inhibitor limits the production of thrombin,which may lead to bleeding risk,but PAR4 can reduce the risk.At present,there are no antithrombotic drugs that the target PAR4.MS-986120 is an inhibitor of PAR4 during the second phase of clinical trials.In this paper,PAR4 was used as a target for computer-aided drug design,and dozens of compounds were virtually selected.The PP260(P1),an indolinone compound with better inhibitory activity,was selected through activity detection.From the perspective of chemical synthesis,P1 derivatives were designed and synthesized.After pharmacological screening,four inhibitors with relatively good inhibitory activity were screened out.We also discussed the structure-activity relationship of these compounds at the same time.Next time,we will try to do a chiral separation experiment and screen out more ideal drug molecules.Part 2.Design,synthesis and activity study of anthraquinonesIt is well known that that tumor metastasis is one of the most important factors of death in cancer patients.In the dominant ways of tumor metastasis,the lymphatic metastasis is the most common way of tumor spread.A new generation of lymph node trackers developed in recent years not only can label lymph nodes but also kill the lymphadenectomy residual tumor cells.As its characteristics of navy blue and anti-tumor activity,the Pixantrone was selected as the prospective lymph node labeling reagent and the Pixantrone Sulfate was screened out as the lymph node tracer.In this paper,we designed and synthesized seven kinds of salt related to Pixantrone and optimized the synthetic route.According to its ideal particle shape,Pixantrone Sulfate was selected as a hopeful lymph node tracer in the future.