Nitrogen-substituted podophyllin derivatives with anti-tumor activity, preparation method and use thereof

Abstract

The invention discloses nitrogen substitution podophyllum type derivatives with antitumor activity and a preparation method and application thereof. The nitrogen substitution podophyllum type derivatives (as formula V) with fine antitumor activity are prepared by introducing 1-(3-amino propyl) imidazole, benzimidazole, 2-thienylmethylamine or trihydroxymethyl aminomethane to C ring 4-position activated by 4-demethylation surface podophyllotoxin. The nitrogen substitution podophyllum type derivatives can act on tumor cells with multiple paths and multiple target points, and accordingly better antitumor curative effect is achieved. Antitumor activity of the derivatives is evidently increased compared with that of the 4-demethylation surface podophyllotoxin. The derivatives can be prepared into antitumor drugs to apply to antitumor therapies.

Description

technical field

[0001] The present invention relates to podophyllotoxin derivatives, in particular to nitrogen-substituted podophyllotoxin derivatives obtained by substituting the 4-position of the C ring of 4'-desmethyl epipodophyllotoxin and a preparation method thereof. The present invention also relates to said The use of nitrogen-substituted podophyllotoxin derivatives in the preparation of antitumor drugs belongs to the field of preparation and application of podophyllotoxin derivatives. Background technique

[0002] Podophyllotoxin and 4′-Demethylepipodophyllotoxin (4′-Demethylepipodophyllotoxin) are extracted from podophyllum plants (for example: Berberidaceae plants Taoerqi, mountain lotus leaf, star anise lotus, etc.) The obtained natural active lead compound with unique antitumor activity. However, Podophyllotoxin or 4'-desmethylepipodophyllotoxin has defects such as low anti-tumor activity to varying degrees, which severely limits their clinical use. Contents ...

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