Pyridine compound and application

Abstract

The invention provides a pyridine compound and application. Based on the find of VEGFR-2 (Vascular Endothelial Growth Factor Receptor-2), EphB4 (Ephrin type-B receptor 4) and TIE-2 compensatory activation, biphenyl arylurea is used as a novel leading compound to analyze conservative conformations of three receptor active sites and find out a general structure region; a molecular hybridization medicine design strategy is adopted to construct a compound library meeting the requirements of the conformations of the general structure region; multi-level activity screening finds out a multi-target inhibitor capable of simultaneously resisting three compensatory paths. A kinase screening test proves that almost pyridine compounds have relatively good kinase inhibition activity; a cell proliferation test proves that almost compounds have relatively strong cell proliferation inhibition activity; structure-activity relationship analysis used as a novel medical effect segment for designing the multi-target inhibitor, and the pyridine compound can be used for preparing an anti-angiogenesis medicine.

Description

technical field [0001] The invention relates to a pyridine compound and its application. Background technique [0002] Anti-angiogenesis is mainly used in the treatment of various angioproliferative diseases including malignant tumors. Designed to reduce blood vessel density and inhibit angiogenesis. It was initially hypothesized that antiangiogenic inhibitors could circumvent typical drug resistance because their target cells are genetically stable endothelial cells. However, multiple proangiogenic factors induce increased tumor invasiveness and subsequent acquired drug resistance, so not all patients benefit from antiangiogenic therapy. [0003] Further studies were conducted to better define the resistance of cancer cells, which allowed them to overcome anti-angiogenic strategies. Acquired resistance to anti-angiogenic inhibitors is mainly caused by compensatory activation of pro-angiogenic factors. Compensatory activation of pro-angiogenic factors enables tumors to e...

AI Technical Summary

Problems solved by technology

[0005] At present, although some innovative progress has been made in the research of anti-angiogenic drugs, there are still the following problems: ① Regulation of angiogenesis is a network involving multiple signaling pathways. After the action of single-target drugs, angiogenesis often appears compensatory. pathway, leading to the generation of drug resistance; ②The target selectivity of the discovered anti-angiogenic drugs is not high, and there are many adverse reactions; ③Single-target anti-angiogenic drugs can only act on one link of the angiogenesis process, and the Multi-factor regulation and its complexity directly limit the effect of single-target drugs

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