Derivatization Research (Ⅲ, Ⅳ) (Ⅲ) Dihydro-pyrazolo [4,3-c] Synthesis And Antitumor Activity Was Measured Hexahydropyridine (Ⅳ) Monocarbonylation Curcumin Analogs With Anticancer Activity Tetrahydro Pyrido [4,3-b] Pyridine Synthesis And Biological

In order to find some lead compounds with activities of anti-cancer, a total oftwo series of57unreported compounds shown in the formula （Ⅲ） and （Ⅳ） weredesigned and synthesized. N-（4-substitutedbenzyl）-3,5-bis（benzylidene）-4-piperidonewere synthesized with substituted amines and methyl acrylate as raw materials via aseries of Michael addition, Dieckmann condensation, hydrolysis decarhoxylation andAdol condensation reactions. With these intermediates,2H-pyrazolo[4,3-c]hexahydropyridine derivatives (Ⅲ₁-Ⅲ₄₁) and tetrahydropyrido[4,3-b]pyridonederivatives (Ⅳ₁-Ⅳ₁₆) were synthesized. The structural formulas of compounds （Ⅲ）and （Ⅳ） are as follows respectively: All these target compounds are new compounds and their structures wereconfirmed by IR,¹H NMR, MS, and elementary analysis. Their physic-chemicalproperties, spectrum properties, reaction conditions and synthetic methods werediscussed as well.Further more, in order to investigate space structure of compounds（Ⅲ）, wenurtured and obtained the crystal structure of compoundⅢ₁by single crystal X-Raydiffraction analysis, it is trans-configuration.The growth inhibition activities of the compoundsⅢ₁-Ⅲ₄₁ against human breastcancer cell lines MCF-7and MDA-MB-231proliferation and compoundsⅣ₁-Ⅳ₁₆against leukemic K562cells, ovarian cancer HO-8910cells and liver cancerSMMC-7721cells proliferation were determined by the MTT assay according to thestandard bioactivity test procedures of the Zooblast-molecular Biology Laboratory ofShanghai Normal University of China. The results indicated that compoundsⅢ₃₃ andⅣ₈showed the best activities respectively. And experimental researches aboutapoptosis was also conducted by the Zooblast-molecular Biology Laboratory ofShanghai Normal University of China.The metabolic stability of compoudsⅢ₂₁,Ⅲ₃₃ in liver microsomes of humanand rat were investigated by central research institute of Shanghai PharmaceuticalsHolding Co.,Ltd.. At the same time we also authorize central research institute of Shanghai Pharmaceuticals Holding Co.,Ltd. To investigate the direct inhibitory effectof compoundⅢ₂₁ in liver microsomes of human. The results indicated that themetabolic stability of compoundⅢ₂₁ in liver microsomes of human and rat is goodand had no direct inhibitory effect on proliferation in liver microsomes of human.