183133-96-2Relevant articles and documents
Preparation method of cabazitaxel
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Paragraph 0016; 0035; 0045-0050; 0059-0061; 0070-0071;....., (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.
Synthesis and biological evaluation of novel cabazitaxel analogues
Ren, Sumei,Zhang, Minmin,Wang, Yujie,Guo, Jia,Wang, Junfei,Li, Yingxia,Ding, Ning
, (2021/06/07)
Cabazitaxel is one of the most recently FDA-approved taxane anticancer agent. In view of the advantages in preclinical and clinical data of cabazitaxel over former toxoids, the synthesis and biological evaluation of novel cabazitaxel analogues were conducted. First, a novel semi-synthesis of cabazitaxel was described. This strategy is concise and efficient, which needs five steps from the 10-deacetylbaccatin III (10-DAB) moiety and a commercially available C13 side chain precursor with a 32% overall yield. Besides, this strategy avoids using many hazardous reagents that involved in the previously reported processes. Then, a panel of cabazitaxel analogues were prepared basing on this strategy. The cytotoxicity evaluations showed that the majority of these cabazitaxel analogues are potent against both A549 and KB cells and their corresponding drug-resistant cell lines KB/VCR, and A549/T, respectively. Further in vivo antitumor efficacies assessment of 7,10-di-O-methylthiomethyl (MTM) modified cabazitaxel (compounds 16 and 19) on SCID mice A549 xenograft model showed they both had similar antitumor activity to the cabazitaxel. Since compound 19 was observed causing more body wight loss on the mice than 16, these preliminary studies suggest 16 might be a potent drug candidate for further preclinical evaluation.
Acid-sensitive PEGylated cabazitaxel prodrugs for antitumor therapy
Liu, Tao,Zou, Hui,Mu, Jingqing,Yu, Na,Xu, Yang,Liu, Guohua,Liang, Xingjie,Guo, Shutao
supporting information, p. 1751 - 1754 (2021/03/08)
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.
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.
Taxane anti-tumor drug KABA docetaxel synthesis method
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, (2017/08/25)
The invention relates to a novel synthesis method of taxane antitumor drug cabazitaxel. The method relates to six-step reaction. Firstly, a key intermediate compound 7 as shown in the specification is obtained, and then reacts with di-tert-butyl dicarbonate ester (Boc)2O, so as to obtain the final product cabazitaxel. The whole reaction process does not relate to low-temperature operation and column chromatography purification, and the method is easy to operate, convenient to purify, and easy in mass production.
Novel cabazitaxel anhydrous compound and preparation method and crystal form thereof
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Paragraph 0045-0046, (2017/08/09)
The invention specifically relates to a cabazitaxel anhydrous compound and a preparation method and crystal form thereof. The method is fewer in steps, mild in reaction conditions, simple and convenient in purification, high in reaction yield, less in pollution, and available in raw materials, and the obtained novel crystal form is stable and facilitates industrial production.
A high-purity kaba he game process for the preparation of intermediate
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, (2017/04/27)
The invention belongs to the technical field of drug synthesis, and particularly relates to a compound (2alpha, 5beta, 7beta, 10beta, 13alpha)-4-(acetyloxy)-13-({(2R, 3S)-3-[(tert-butoxycarbonyl)amino]-2-[2-methoxy-2-prop-2-yl]oxy]-3-phenylpropionyl}oxy)-1,7,10-trimethoxy-9-oxo-5,20-epoxy-11-ene-2-yl benzoate (compound II, namely '7, 10, 13-trimethoxy-10-DAB'). The invention also relates to a preparation method of high-purity (2alpha, 5beta, 7beta, 10beta, 13alpha)-4-(acetyloxy)-13-({(2R, 3S)-3-[(tert-butoxycarbonyl)amino]-2-[2-methoxy-2-prop-2-yl]oxy]-3-phenylpropionyl}oxy)-1-hydroxy-7,10-dimethoxy-9-oxo-5,20-epoxy-11-ene-2-yl benzoate (compound 1). The preparation method comprises the steps of silica gel chromatographic column chromatography and recrystallization. In the compound I prepared by the preparation method, the content of impurities compound II and compound III is remarkably reduced. The compounds I and III can be used for preparing an anti-cancer drug cabazitaxel.
Kaba he of the intermediate compounds (by machine translation)
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Paragraph 0176 - 0178, (2017/05/25)
The present invention relates to intermediate compounds of Kabbah, in particular for the preparation of the intermediate compound he Kabbah 6, preparation method thereof, and he Kabbah for preparing the compound of the method. Intermediates to of the present invention the process of preparing kaba he races, in each step of the reaction time is greatly shortened, the reaction yield is greatly improved, greatly reduces the cost of synthesizing of Kabbah. (by machine translation)
NOVEL METHOD FOR PREPARING CABAZITAXEL FROM 10-DEACETYLBACCATIN III IN HIGH YIELD, AND NOVEL INTERMEDIATE THEREFOR
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, (2015/11/03)
The present invention relates to a novel method for preparing cabazitaxel from 10-deacetylbaccatin III, and a novel intermediate therefor, and more specifically, to: a method which allows cabazitaxel to be more easily prepared in a high yield and in a high purity within a short time compared with a conventional method by preparing cabazitaxel via a novel intermediate using 10-deacetylbaccatin III as a starting material, and thus is suitable for industrial mass production; and a novel intermediate therefor.
PROCESS FOR THE PREPARATION OF CABAZITAXEL AND ITS SOLVATES
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Page/Page column 18; 19; 20, (2015/06/25)
The present disclosure provides anisole and benzyl alcohol solvates of cabazitaxel and methods of their production. The solvates may be characterized by powder x-ray diffraction patterns. The present disclosure also provides methods for the synthesis of cabazitaxel.
