Synthesis And Activity Screening Of Novel Small Molecule Self - Phagocytic Inhibitors

Autophagy is a general designation intracellular substances degraded by cells depending on lysosome.Scientists found that Autophagy played a very important role not only in cell growth and development but also in disease during recent research.Now,Autophagy shows a good prospect in a new research field.In this dissertation,the definition of Autophgy,the morphological features and classification of Autophagy,the important role of Autophagy in physiology and pathophysiology were introduced concisely.At the same time,the development of Autophagy inhibitors was reviewed. MBCQ was obtained by HCS from thousands of compounds in our lab,which had good autophagy inhibitory activity induced by rapamycin under electron microscope,the EC₅₀was 0.778μM.MBCQ was used as a lead copmpound,36 new quinazoline derivatives were designed and synthesized by using bioisosterism.All the target compounds and intermediates were confirmed by ¹H-NMR and ESI-MS,some of them were confirmed by ¹³C-NMR and HR-MS.Primary pharmacological tests showed that some of the compounds had good inhibitory activities,while XLH29 was the best inhibitor during recent research,the EC₅₀was 0.083μM.