Synthesis And Qsar. Bifendate Analogues

SYNTHESIS OF DERiVATIVESOF ~ -DDB AM) STUDY OF THEIR QSARYue hongyi (Medicinal Chemistry)Tutor:Zeng zhaojunABSTRACT4,4?-Dimethoxy-5,6, 5?,6?-bis(methylenedioxy)-2,2 ?-dimethoxycarbonyl biphenyl (Y -DDB), which was discovered in the process of studying the antihepatotoxic components from Schizandra chinensis, has been well known as an effective agent for liver protect. It can decrease hepatic damage and hepatocytes necrosis induced by some chemical substance such as carbon tetrachloride, Dgalactosamin or thioacetamide, lower the level of syrum glutamic-pyrumic transaminase(GPT) and glutamic-oxalacetic transaminase (GOT), relieve the symptom of intoxicant heptitis caused by chemotherapic agents such as Fluorouracil Methotrexate. Y -DDB has no mutagenicity or malformationity and low toxicity. But studies on the disposition of ~?-DDB showed that it can be destroyed in gastrol or intestinal and little is absorbed. 24 hours after administration orally, 78.4% of the dosage can be recovered. ~O?O% is absorbed to draw a strong ability of decrease the activity of GPT. That is to say i?-DDB has a good biologic activity but a poor bioavialability.In order to decrease its side-effects and increase its bioavialability , we synthesized 17 derivatives of y -DDB, 15 of which were new compounds. Their structures were confirmed by NMIR and MS The pharmacological test showed that these compounds could lower the level of syrum GPT significantly. At the same time we summarized some laws of QSAR about these compounds.