Cabazitaxel CAS 183133-96-2
Introduction：Basic information about Cabazitaxel CAS 183133-96-2, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Cabazitaxel Basic informationAntitumour Activity Pharmacokinetics
| Product Name: | Cabazitaxel |
| Synonyms: | (2AR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9-(((2R,3S)-3-((tert-butoxycarbonyl)amino)-2-;TXD-258;(αR,βS)-β-[[(1,1-DiMethylethoxy)carbonyl]aMino]-α-hydroxybenzenepropanoic Acid (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(Acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-11-hydroxy-4,6-diMethoxy-4a,8,13,13-tetraMethyl-5-oxo-7,11-Methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl Ester;XRP 6258;Cabazitaxel;XRP6258;RPR-116258A;TAXOID XRP6258;TXD 258;CS-877;Cabazitaxel 183133-96-2 |
| CAS: | 183133-96-2 |
| MF: | C45H57NO14 |
| MW: | 835.93 |
| EINECS: | 680-632-7 |
| Product Categories: | API;XRP-6258;Aromatics;Plant extracts;Herb extract;Final material;Pharmaceutical intermediate;Chiral Reagents;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;APIs |
| Mol File: | 183133-96-2.mol |
Cabazitaxel Chemical Properties
| Melting point | 180 °C |
| Boiling point | 870.7±65.0 °C(Predicted) |
| density | 1.31 |
| storage temp. | Inert atmosphere,Store in freezer, under -20°C |
| solubility | Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly) |
| pka | 11.20±0.46(Predicted) |
| form | White solid. |
| color | White to Off-White |
| Optical Rotation | [α]/D -36 to -44°, c =0.5 in methanol |
| InChIKey | BMQGVNUXMIRLCK-JACFBOAKNA-N |
Safety Information
| Safety Statements | 24/25 |
| WGK Germany | WGK 2 |
| HS Code | 29329990 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Acute Tox. 4 Oral Muta. 2 Repr. 2 Skin Irrit. 2 STOT RE 2 |
| Antitumour Activity | Cabazitaxel is a semisynthetic taxane derivative that acts as a microtubule inhibitor. It binds to tubulin, promoting the assembly of tubulin into microtubules and inhibiting their disassembly, which results in microtubule stabilization, the inhibition of cell division, cell cycle arrest and the arrest of tumour proliferation. Cabazitaxel demonstrated antitumour activity against advanced human tumours xenografted in mice. As well as being active in docetaxel-sensitive tumours, cabazitaxel showed activity in tumour models insensitive to chemotherapy, including docetaxel. Cabazitaxel also penetrates the blood-brain barrier to a greater extent than docetaxel. |
| Pharmacokinetics | The pharmacokinetic data for cabazitaxel demonstrated dose proportionality, with a high plasma clearance and a long terminal half-life. The very large volume of distribution at steady state suggests extensive penetration into tissues. Of interest, cabazitaxel is able to cross the blood-brain barrier in preclinical models. Cabazitaxel is mainly metabolized by the cytochrome P450 (CYP) enzyme 3A4/5 and to a lesser extent by CYP2C8, suggesting that it has the potential to inhibit CYP3A enzymes. |
| Description | In June 2010, the U.S. FDA approved cabazitaxel (also referred to asXRP6258 and RPR 116258A) in combination with the steroid prednisonefor the treatment of metastatic Castration-Resistant Prostate Cancer(mCRPC) for patients who were previously treated with a docetaxelcontainingregimen for late-stage disease. Cabazitaxel is a semisynthetic analog of thenatural product taxol, which is isolated from the bark of the yew tree.Cabazitaxel is a microtubule inhibitor that binds to the taxol-binding site oftubulin. Similar to other tubulin inhibitors of the taxol class, cabazitaxelinhibits microtubule disassembly resulting in mitotic blockade and celldeath. Docetaxel, also a semisynthetic taxol analog, was approved by theFDA for the treatment of mCRPC in 2004. However, docetaxel is a substratefor P-gp, which is thought to contribute to the constitutive and acquiredresistance of cancer cells to taxanes. Cabazitaxel has poor affinity for P-gpand showed antitumor activity in preclinical in vitro studies and in vivotumor models that overexpress this protein. Cabazitaxel is synthesized ona commercial scale from 10-deacetylbaccatin . |
| Chemical Properties | White solid |
| Originator | Sanofi-Aventis (France) |
| Uses | Cabazitaxel (Jevtana, XRP6258) is a semi-synthetic derivative of a natural taxoid. |
| Uses | A novel semi-synthetic taxane with antitumor activity used for the treatment of castration-resistant prostate cancer. A microtubule inhibitor. |
| Definition | ChEBI: A tetracyclic diterpenoid that is 10-deacetylbaccatin III having O-methyl groups attached at positions 7 and 10 as well as an O-(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hyroxy-3-phenylpropanoyl group attached at position 13. Acts as a microtubule inhibitor, binds tubulin and promotes microtubule assembly and simultaneously inhibits disassembly. |
| Brand name | Jevtana |
| Clinical Use | Cabazitaxel was developed by Sanofi-Aventis as an intravenous injectable drug for the treatment ofhormone-refractory metastatic prostate cancer. As a microtubule inhibitor, cabazitaxel differs from docetaxel because it exhibits a much weaker affinity for P-glycoprotein (P-gp), an adenosinetriphosphate (ATP)-dependent drug efflux pump. Cancer cells that express P-gp become resistantto taxanes, and the effectiveness of docetaxel can be limited by its high substrate affinity for P-gp.Clinical studies confirmed that cabazitaxel retains activity in docetaxel-resistant tumors. Commonadverse events with cabazitaxel include diarrhea and neutropenia. Cabazitaxel in combination withprednisone is an important new treatment option for men with docetaxel-refractory metastatic CRPC(castration-resistant prostate cancer). |
| Synthesis | The semi-synthesis of cabazitaxel started from 10-deacetylbaccatin III (15) which can be prepared from 7-xylosyl-10-deacetylbaccatin natural productmixture according to a literature process procedure (the Scheme). 10-Deacetylbaccatin III wasprotected with triethylsilyl chloride (TESCl) in pyridine to afford the corresponding 7,13-bis-silyl etherin 51% yield, which was methylated with MeI and NaH in DMF to give 10-methoxy-7,13-bis silyl ether16 in 76% yield. After de-silylation of 16 with triethylamine trihydrofluoride complex at roomtemperature, triol 17 was obtained in 77% yield. Selective methylation of 17 with MeI and NaH inDMF at 0 oC provided 7,10-dimethyl ether 18 in 74% yield. Compound 18 was condensed withcommercially available oxazolidinecarboxylic acid 19 in the presence ofdicyclohexylcarbodiimide/dimethylaminopyridine (DCC/DMAP) in ethyl acetate at room temperatureto generate ester 20 in 76% yield. The oxazolidine moiety of compound 20 was selectively hydrolyzedunder mild acidic conditions to yield the hydroxy Boc-amino ester derivative cabazitaxel (III) in 32%yield. |
| Drug interactions | Potentially hazardous interactions with other drugs Antibacterials: Avoid with clarithromycin, rifabutin, rifampicin and telithromycin. Antidepressants: Avoid with St John's wort. Antiepileptics: Avoid with carbamazepine, fosphenytoin, phenobarbital, phenytoin and primidone. Antifungals: Avoid with itraconazole, ketoconazole and voriconazole. Antipsychotics: Avoid with clozapine (increased risk of agranulocytosis). Antivirals: Avoid with atazanavir, indinavir, ritonavir and saquinavir. |
| Metabolism | Extensively metabolised in the liver (>95%), mainly by the CYP3A4 isoenzyme (80-90%). Cabazitaxel is the main circulating compound in human plasma. Seven metabolites were detected in plasma (including 3 active metabolites issued form O-demethylations), with the main one accounting for 5% of parent exposure.Excreted as metabolites into the urine (4%) and faeces (76%). |
Cabazitaxel Preparation Products And Raw materials
| Raw materials | Benzenepropanoic acid, β-[[(1,1-dimethylethoxy)carbonyl]amino]-α-(1-ethoxyethoxy)-, (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-11-hydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester, (αR,βS)--->Benzenepropanoic acid, β-[[(1,1-dimethylethoxy)carbonyl]amino]-α-[(tetrahydro-2H-pyran-2-yl)oxy]-, (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-11-hydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester, (αR,βS)--->1380584-07-5-->N',O'-(4-Methoxybenzylidene)cabazitaxel-->Cabazitaxel N-1 |
