N-aryl-β-carbolin derivatives and uses thereof

Abstract

The present invention relates to the field of pharmaceutical technology, in particular to N-aryl-β-carbolin derivatives and uses thereof; the synthesis method of the N-aryl-β-carbolin derivatives of the present invention is simple, and the steps are simple and convenient. First use tryptophan methyl ester and aldehyde derivatives to react to obtain indolopyrrole intermediates, then add an oxidant to obtain β-carbolin, and finally couple aromatic ring derivatives under alkaline conditions to obtain the β-carbolin of the present invention. N-aryl-β-carbolin derivatives have low cardiomyocyte toxicity, strong protective ability and high activity, which improves the application of carbolin derivatives in myocardial hypoxia-reoxygenation injury.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to N-aryl-β-carbolin derivatives and applications thereof. Background technique [0002] Coronary atherosclerotic heart disease is one of the most common diseases that threaten human health, and its incidence is on the rise. Nowadays, cardiovascular and cerebrovascular diseases have become the main diseases leading to human death. Ischemic heart disease is reported to be the leading cause of mortality worldwide, accounting for 8 million deaths in 2013. At present, the main means of treating coronary atherosclerosis is to quickly open the arteries related to myocardial blockage, so that the coronary artery bypass graft can be reperfused. However, studies have found that these treatments are accompanied by myocardial ischemia-reperfusion injury (MI / RI), which leads to further damage to myocardial cells. MIRI has become one of the important factors leading to death due to myocardia...

AI Technical Summary

Problems solved by technology

There are currently 4 isomers, among which 3-carboline is also called β-carboline and β-carbolin. Its natural products have a series of biological activities such as anti-inflammatory, bactericidal, cytotoxic, and anti-cancer properties. In the document "Regulatory Effects of β-Carboline and Feridone Alkaloids on Inflammatory Signal Transduction Pathways", it is reported that β-carbolin alkaloids have anti-HIV, anti-inflammatory, antibacterial, and inhibitory activities of monoammonia oxidase etc. Patent No. CN201910584227.8 Extraction process and application of β-carbolin-type alkaloids in bitterwood, discloses the application of β-carbolin-type alkaloids in bitterwood for the preparation of anti-tumor drugs; but at present, most Most β-carbolins are obtained by extracting natural substances, and the yield and purity are extremely low, which seriously affects their development and application, and there are few studies on the anti-myocardial hypoxia-reoxygenation injury of β-carbolin derivatives

[0004] Patent No. CN201810124764X reported that α-carbolin derivatives have anti-hypoxia-reoxygenation injury activity in cardiomyocytes. However, the synthesis steps of α-carbolin’s mother nucleus are long and the yield is low, especially when benzotriazole is used in multiple Removal of N under the action of polyphosphoric acid 2 The yield of α-carborine obtained by ring closure after the molecule is only about 20%, and the total yield is lower than 10%, which limits the development of carbolin derivatives. At the same time, studies have shown that the cardiomyocyte toxicity of α-carborin derivatives is relatively large, and the anti-cardiomyocyte hypoxia-reoxygenation injury activity is not significant enough, which seriously restricts the application of carbolin derivatives in cardiomyocyte protection

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