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Design and Synthesis of Anti-tumor Protein Tyrosine Kinase Inhibitor

Author: LiYinKe
Tutor: CaiZhengHong
School: Southwest Jiaotong University
Course: Pharmacognosy
Keywords: Anti-tumor Protein tyrosine kinase inhibitors Design Synthesis
CLC: R914
Type: Master's thesis
Year: 2011
Downloads: 106
Quote: 0
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Abstract


Phosphorylation of tyrosine residues of protein tyrosine kinase can catalyze a variety of substrate proteins , cell growth , proliferation , differentiation and apoptosis plays an important role . Seen in many cancer cell type tyrosine kinase receptor overexpression or activation , the event will not only lead to cell-mediated disorder , intracellular signaling abnormal activation , cell transformation , continuous proliferation , resistance to apoptosis induced by tumor , but also with tumor invasion and metastasis , tumor angiogenesis , tumor resistance to chemotherapy and radiotherapy is closely related . Effectively inhibit protein tyrosine kinase activity , can achieve the purpose of treatment of cancer . Therefore, the research and development of protein tyrosine kinase inhibitors has become the research focus of anticancer drugs . The papers in the series of tyrosine kinase inhibitor structure-activity relationship studies on the basis of the literature using homology modeling and molecular docking speculated inhibitors - enzyme binding mode , the use of computer-aided design , design and the synthesis of a series of 6 - substituted the aminobenzoyl indole ketone derivative and 4 - substituted indirubin derivatives as the antineoplastic protein tyrosine kinase inhibitor activity screening candidate compounds . 6 - substituted the aminobenzoyl indole ketone derivative synthesis method is discussed . That should not be used in the synthesis of the indole ring of Sn and hydrochloric acid One-Pot Synthesis byproduct of the law , a serious loss of product ; and decarboxylation - ring-closing less byproducts , high yield, more viable . This thesis synthesis of the target compound 19 , indole ketones 16 , Indirubin compounds 3 . All compounds are all characterized by 1H - NMR ( 600 MHz ) and MS (ESI) confirmatory structure , wherein the intermediate product after the identification of the 13C-NMR ( 600 MHz ) .

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CLC: > Medicine, health > Pharmacy > Drug basic science > Medicinal Chemistry
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