1714967-27-7Relevant articles and documents
Acid-sensitive PEGylated cabazitaxel prodrugs for antitumor therapy
Liu, Tao,Zou, Hui,Mu, Jingqing,Yu, Na,Xu, Yang,Liu, Guohua,Liang, Xingjie,Guo, Shutao
, p. 1751 - 1754 (2021)
Although the antitumor drug cabazitaxel shows great therapeutic potential, its high toxicity and poor water solubility limit its utility. However, the use of stimuli-responsive prodrugs is a promising strategy for overcoming these limitations. Herein, we report the synthesis of two highly water soluble, acid-sensitive PEGylated acyclic-ketal-linked cabazitaxel prodrugs (PKCs) with improved antitumor efficacy. In an acidic tumor microenvironment, the PKCs hydrolyzed rapidly to release the native drug, whereas they were stable in the normal physiological environment. Compared with cabazitaxel injection, the PKCs had much higher maximum tolerated doses; and in an MDA-MB-231 subcutaneous xenograft nude mouse model, the PKCs showed better antitumor efficacy and safety than cabazitaxel injection. The prodrug strategy reported herein could be useful for the development of other water soluble, acid-sensitive prodrugs with improved efficacy.
Preparation method of cabazitaxel
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, (2021/11/27)
The invention discloses a preparation method of cabazitaxel, which comprises the following specific steps: dissolving 10-deacetylbaccatin III with dichloromethane and pyridine, dropwise adding 2,2,2-trichloroethyl chloroformate, and treating to obtain an intermediate I; mixing toluene, 4-dimethylaminopyridine, the intermediate I and (4S,5R)-3-tert-butoxycarbony-2-(4-anisy)- 4-phenyl-5-oxazolidinecarboxylic acid, stirring, dropwise adding N,N'-dicyclohexylcarbodiimide, and stirring for reaction to obtain an intermediate II; dissolving the intermediate II with ethyl acetate and acetic acid, adding zinc powder, carrying out a stirring reaction to obtain an intermediate III, dissolving the intermediate III with dichloromethane, adding 1,8-bis(dimethylamino)naphthalene, a molecular sieve and trimethyloxonium tetrafluoroborate, and carrying out a stirring reaction to obtain an intermediate IV; dissolving and clarifying the intermediate IV with methanol, dropwise adding a hydrochloric acid methanol solution having a concentration of 1mol/L, and stirring for reaction to obtain cabazitaxel. According to the method, methylation can be realized at room temperature, the product purity is good, the yield is high, starting materials are easy to obtain, and large-scale preparation can be carried out.
Method for synthesizing cabazitaxel by using 10-deacetylbaccatin III
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Paragraph 0017; 0019; 0020; 0023; 0027, (2018/06/23)
The invention discloses a method for synthesizing cabazitaxel by using 10-deacetylbaccatin III. The method comprises the steps of under the condition of existence of a solvent, a catalyst, and an anti-degradation agent, preparing a cabazitaxel intermediate 7,10-methoxy baccatin III by using 10-deacetylbaccatin III as a starting material; then, under the condition of existence of the catalyst and anti-degradation agent, performing a condensation reaction on the cabazitaxel intermediate 7,10-methoxy baccatin III and a side chain of docetaxel so as to prepare a cabazitaxel precursor N-1; performing hydrolyzation and ring opening on the cabazitaxel precursor N-1 under the acid condition, so as to obtain a crude cabazitaxel product; and performing column chromatography, crystallization, recrystallization and purification on the crude product so as to obtain the cabazitaxel. The method is low in cost and high in yield, the prepared product has high purity and contains fewer impurities, and the method is suitable for industrial production and promotion in the market.
