Macromolecule vinblastine conjugate adopting amino acids or oligopeptides as connexons

Abstract

The invention relates to a macromolecule vinblastine conjugate adopting amino acids or oligopeptides as connexons. Specifically, the invention relates to a conjugate represented by a formula I, or pharmaceutically-acceptable salts thereof. The conjugate is prepared by conjugating a biocompatible macromolecule and vinblastine through amino acids or oligopeptides, wherein each symbol in the formula I is described in an instruction. The invention further relates to a method for preparing the conjugate or the pharmaceutically-acceptable salts thereof, drug combinations combined through the conjugate and the pharmaceutically-acceptable salts thereof, application in medicine for treating and / or preventing proliferative disease, neoplastic disease or carcinoma disease. According to the present invention, hydroxy group on C-4 of the vinblastine or the hydroxy group on the deacetylated C-4 of derivatives is adopted as a cross-linked group, and is conjugated with the macromolecule through the amino acids or the oligopeptides to obtain an effective conjugate of the vinblastine with novel characteristic.

Description

Macromolecule-vinblastine conjugate with amino acid or oligopeptide as linker technical field The invention relates to a conjugate formed by a biocompatible macromolecule through an amino acid or an oligopeptide and a vinblastine drug and a non-toxic pharmaceutically acceptable salt thereof, wherein the vinblastine drug is vinblastine, vincristine, and vindesine , Vinrelbine and Vinflunine. Background technique Vinblastine drugs are the most commonly used antineoplastic drugs clinically, including vinblastine, vincristine, vindesine, vinorelbine and vinflunine. The chemical structures of vinblastine drugs are shown below: Vinblastine antineoplastic drugs can not only bind to tubulin and inhibit the polymerization of tubulin double microsomes into microtubules; Cancer cells divide and multiply. Vinblastine is a representative of vinblastine drugs, mainly effective for lymphoma, choriocarcinoma and testicular tumors, and also effective for other cancers such as lung canc...

AI Technical Summary

Problems solved by technology

Although vinblastine drugs are widely used clinically, as cytotoxic antineoplastic drugs, these drugs have side effects such as bone marrow suppression and gastrointestinal reactions, and the adverse reactions are large.

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