Aryl nitrogen mustard-domide conjugate and preparation method and pharmaceutical application thereof

Abstract

The invention discloses an aryl nitrogen mustard-domide conjugate and a preparation method and pharmaceutical application thereof. Compound (1) is subjected to reaction with compound (2) in the presence of polypeptide condensing agents EDCI and DMAP, or HATU and DIPEA to obtain compound I that is used to prepare antitumor drugs. The two drugs of different target types are combined herein to form aprodrug; multi-action synergic antitumor effect is achieved; antitumor activity and tolerance are improved; drug resistance of tumors is decreased. The domide drugs are linked via amido bonds, so that chances for amino groups on domide benzene rings to be degraded by in-vivo enzymes can be slimmed, and in-vivo bioavailability of the drugs is improved.

Description

technical field

[0001] The present invention relates to the field of biomedicine, in particular to a class of aromatic nitrogen mustard-mildamine conjugates and pharmaceutically acceptable salts thereof, their preparation methods, pharmaceutical compositions containing these derivatives and their medical applications, Especially the application in the preparation of antitumor drugs. Background technique

[0002] The chemical name of Lenalidomide is 3-(4-amino-1,3-dihydro-1-oxo-2H-isoindol-2-yl)-2,6-piperidinedione, which is An important derivative of thalidomide is the second-generation oral immunomodulatory drug developed by Celgene Corporation of the United States. It has dual mechanisms of inhibiting tumor necrosis factor and inhibiting tumor angiogenesis. On the one hand, it can directly The anti-cancer effect can effectively inhibit the development of cancer cells and induce the death of cancer cells. On the other hand, it can regulate the immune function of patients a...

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