A kind of 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 application. Background technique [0002] Anti-angiogenesis is mainly used in the treatment of various vascular proliferative diseases including malignant tumors. Designed to reduce blood vessel density and inhibit angiogenesis. It was initially hypothesized that anti-angiogenesis inhibitors can circumvent typical drug resistance because their target cells are genetically stable endothelial cells. However, a variety of pro-angiogenic factors induced increased tumor invasiveness and subsequent drug resistance, so not all patients benefited from anti-angiogenic therapy. [0003] In order to better determine the resistance of cancer cells, more in-depth research has been done, which allows them to overcome anti-angiogenesis strategies. The acquired resistance of anti-angiogenesis inhibitors is mainly caused by the compensatory activation of pro-angiogenic factors. The compensatory activation of pro-angiogenic...

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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