4-substituted anilino-podophyllotoxine derivative and application

Abstract

The invention provides a 4-substituted anilino-podophyllotoxine derivative which refers to a 4'-O-demethyl-4-deoxy-4-substituted anilino-podophyllotoxine derivative. A series of compounds with anti-cancer activity is synthetized by taking the traditional drug etoposide as a lead compound by structural transformation; primary in vitro screening and in vivo antitumor tests show that the compounds have better anti-tumor activity, wherein when the compound GL3 improves the anti-tumor action, the toxicity of the compound GL3 is obviously reduced, and thereby, the compound GL3 can be used for preparing anti-tumor drugs which has higher antitumor activity and lower toxicity and has effect on multi-drug drug resistant tumors. The structural general formula of the 4-substituted anilino-podophyllotoxine derivative is shown in the specification.

Description

technical field The invention belongs to the preparation and use of compounds, and mainly relates to the preparation of 4'-O-desmethyl-4-deoxy-4-substituted anilino epipodophyllotoxin derivatives and their application in the preparation of antitumor drugs. Background technique Etoposide and teniposide are currently clinically used antineoplastic drugs, both of which are semi-synthetic derivatives of 4'-O-desmethyl epipodophyllotoxin. 4'-O-desmethyl epipodophyllotoxin derivatives can destroy the structure and function of DNA by inhibiting the activity of DNA topoisomerase II, thereby exerting an anti-tumor effect. Although the above two compounds have been used clinically for many years, they still have problems such as poor water solubility, bone marrow suppression, and easy drug resistance, which limit their application. Therefore, in order to overcome the above shortcomings and find more efficient and low-toxic podophyllotoxin compounds, researchers have carried out a se...

AI Technical Summary

Problems solved by technology

Although the above two compounds have been used clinically for many years, there are still problems such as poor water solubility, bone marrow suppression, and easy drug resistance, which limit their application.

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