7-azaindirubin and 7-azaisoindigo derivative, its production and pharmaceutical use

Abstract

A method for designing and synthesizing 7-azaindirubin and 7-azaisoindigo derivative and its medicinal use are disclosed. It changes indirubin and isoindigo nuclear-parent molecule atomic composition to form into compound. It also changes original molecule electric property. The process is carried out by coupling at different position by 7-azaindole and indole bi-molecule, inhibiting CDKs and CDKIs growth and breed and inducing CDKIs biological function. It can be used to treat malignant tumor, HIV and nervous system diseases.

Description

technical field [0001] The present invention relates to a method for designing and synthesizing a class of novel structure 7-azaidirubin and 7-azaiisoindigo derivatives and their pharmaceutical application. The common feature of these molecules is that they are all formed by coupling 7-azaindole and indole bimolecules at different positions, and inhibit cell growth and proliferation through various mechanisms, including inhibition of cyclin-dependent kinases ( Cyclin-dependent kinases, referred to as cell cycle kinases, abbreviated as CDKs), inducing endogenous cell cycle kinase inhibitors (CDKIs) and other biological functions, and then have the ability to treat various diseases caused by cell growth disorders, including malignant tumors, Neurological diseases such as viral skin diseases, HIV, neurodegeneration and disorders, etc. Background technique [0002] The cyclin-dependent kinases (cyclin-dependent kinases, abbreviated as cell cycle kinases, abbreviated as CDKs) fa...

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Problems solved by technology

[0006] In summary, indirubin-like bisindole compounds are an important class of CDKs inhibitors with low toxicity and side effects, but their fat-solubility and water-solubility are poor, which affects their clinical application. In recent years, foreign Many pharmaceutical research institutes and pharmaceutical companies have carried out extensive structural modifications to indirubin compounds (WO: 99 / 62503, 1999-12-9; WO: 01 / 37819 A2, 2001-8-31; WO: 00 / 61555, 2000-10-19; US pat: 2002 / 0132792 A1, 2002-9-19), the properties such as the dissolution of these compounds are improved to varying degrees, in order to further improve the antitumor properties of indirubin bisindole compounds effect, it is necessary to make major changes to the structure of such compounds

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