Design, Synthesis And Anti-tumor Evaluation Of Azaoxindoles,5-fluorooxindoles, And Synthesis Of 2-(Piperazin-l-yl) Benzamides Library

Most of the signal transduction pathways are mediated by protein kinases regulating every aspect of cell function including cell growth, differentiation, migration, and apoptosis. Overexpressed Protein kinases were result in many diseases such as cancers. Protein tyrosine kinases are a kind of the main protein kinase. In recent years, with protein tyrosine kinases target inhibitor study more and more, cancer treatment has been achieved in encouraging important progress. There are two classes of PTKs present in cells:the receptor protein tyrosine kinases and the nonreceptor protein tyrosine kinases. The first chapter of the paper will introduce protein tyrosine kinases and clinical listed drugs.Dissertation chart 2 mainly introduces the synthesis of azaoxindole and 5-fluorooxindole derivatives (sixty) which are on the basis of the drug of sunitinib. A series of indolin-2-ones were found to have moderate antitumor activity against the selected tumor cell lines. Compounds ZHL2010-g were found to have more potent cytotoxicity (IC50=12.97μM and 15.78μM) against KB cell line and the K562 cell line compared to Sunitinib (IC50=21.91μM and 21.97μM).Compound library is the source of new drug development. So the quality and scale of the compound libraries in new drug development plays an important role. The third chapter of paper briefly introduces compound library construction (442), the antitumor activity screening are still in progress.