N-aryl-beta-carboline derivatives and application thereof

Abstract

The invention relates to the technical field of medicines, and concretely relates to N-aryl-beta-carboline derivatives and an application thereof. The synthesis method of the N-aryl-beta-carboline derivatives is simple, and simple in steps. The method comprises the following steps: reacting tryptophan methyl ester with an aldehyde derivative to obtain an indolopyrrole intermediate, then adding anoxidizing agent, performing cyclization to obtain beta-carboline, and finally coupling with aromatic ring derivatives under an alkaline condition to obtain the N-aryl-beta-carboline derivatives. The compounds are low in myocardial cell toxicity, strong in protection capability and high in activity, and the application of the carboline derivatives in myocardial anoxia reoxygenation injury is improved.

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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