Ixabepilone

Base Information

• Chemical Name: Ixabepilone
• CAS No.: 219989-84-1
• Molecular Formula: C27H42N2O5S
• Molecular Weight: 506.707
• Hs Code.: 2941906000
• European Community (EC) Number: 630-424-7
• NSC Number: 747973
• UNII: K27005NP0A
• DSSTox Substance ID: DTXSID70870252
• Nikkaji Number: J1.408.120H
• Wikipedia: Ixabepilone
• Wikidata: Q11711607
• NCI Thesaurus Code: C37452
• RXCUI: 337523
• Pharos Ligand ID: BFPU6BQD7ZJH
• Metabolomics Workbench ID: 62862
• ChEMBL ID: CHEMBL1201752
• Mol file: 219989-84-1.mol

Synonyms:azaepothilone B;BMS 247550;BMS-247550;BMS247550;ixabepilone

Chemical Property of Ixabepilone

Chemical Property:

• Vapor Pressure: 1.93E-20mmHg at 25°C
• Refractive Index: 1.532
• Boiling Point: 697.815 °C at 760 mmHg
• PKA: 13.73±0.70(Predicted)
• Flash Point: 375.825 °C
• PSA: 140.29000
• Density: 1.122 g/cm³
• LogP: 4.37930
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility.: Chloroform (Slightly), Methanol (Slightly)
• XLogP3: 3.6
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 2
• Exact Mass: 506.28144362
• Heavy Atom Count: 35
• Complexity: 817

Purity/Quality:

99% ^*data from raw suppliers

Ixabepilone ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC1CCCC2(C(O2)CC(NC(=O)CC(C(C(=O)C(C1O)C)(C)C)O)C(=CC3=CSC(=N3)C)C)C
• Isomeric SMILES: C[C@H]1CCC[C@@]2([C@@H](O2)C[C@H](NC(=O)C[C@@H](C(C(=O)[C@@H]([C@H]1O)C)(C)C)O)/C(=C/C3=CSC(=N3)C)/C)C
• Recent ClinicalTrials: Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy
• Recent EU Clinical Trials: Phase II, open label, single arm study to investigate anti-tumor effect of ixabepilone in patients with locally recurrent metastatic breast cancer (mBC) selected by the ixabepilone Drug Response Prediction (DRP) after failure of an anthracycline and a taxane
• Description: Ixabepilone, a semisynthetic analog of epothilone B, was launched for the treatment of metastatic or locally advanced breast cancer. It is indicated for use in combination with capecitabine in patients who have previously failed treatment with an anthracycline such as doxorubicin and a taxane such as paclitaxel. It is also approved as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine. Ixabepilone is the first member of the epothilone family of anticancer agents to be approved. Epothilones are novel cytotoxic macrolides derived from bacterial fermentation.Like the taxanes, their mechanism of action involves binding to and stabilizing microtubules, which results in mitotic arrest and apoptosis. The most common adverse reactions (X20%) associated with ixabelipone as monotherapy or in combination with capecitabine were peripheral sensory neuropathy, fatigue/asthenia, myalgia/arthralgia, alopecia, nausea, vomiting, stomatitis/ mucositis, diarrhea, and musculoskeletal pain. The most common hematologic abnormalities (W 40%) include neutropenia, leukopenia, anemia, and thrombocytopenia. Ixabelipone in combination with capecitabine is contraindicated in patients with AST or ALT W2.5 ULN (upper limit of normal) or bilirubin W1 ULN due to increased risk of toxicity and neutropenia-related death. Ixabepilone is an epothilone with broad-spectrum anticancer activity against a panel of 21 cancer cell lines (IC50s = 1.4-34.5 nM). It stabilizes and induces the polymerization of microtubules and induces cell cycle arrest during mitosis. Ixabepilone is cytotoxic to HCT116/VM46 and A2780Tax clonogenic cells, which are resistant to paclitaxel (; IC90s = 16 and 12.3 nM, respectively, for colony growth inhibition). In vivo, ixabepilone (6.3 and 10 mg/kg, i.v., respectively) shows antitumor activity in paclitaxel-resistant human Pat-21 breast carcinoma and HCT116/VM46 colon carcinoma mouse xenograft models with log cell kill (LCK) values of 1.6 and 2.4, respectively. Ixabepilone (10 mg/kg, i.v.) also increases the time for tumors to quadruple in volume by 7.2, 9, 6.5, 4.7, and >10 weeks, respectively, in mice implanted with Rh18 rhabdomyosarcoma, NB1643 neuroblastoma, WT5 Wilms'' tumor, OS29 osteosarcoma, and BT29 brain carcinoma cells. Formulations containing ixabepilone have used in the treatment of metastatic breast cancer.
• Uses: Ixabepilone is an anti-tumor agent used in the treatment of patients suffering from solid tumors, such as metastatic breast cancer. Antineoplastic; antimitotic.

Technology Process of Ixabepilone

There total 75 articles about Ixabepilone which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 69.0%

[4S-[4R*,7S*,8R*,9R*,15R*(E)]]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-1-aza-13(Z)-cyclohexadecene-2,6-dione (219989-87-4) → ixabepilone (219989-84-1)

Guidance literature:

With DMDO; In dichloromethane; at -78 - -50 ℃; for 1h;

DOI:10.1021/jo010275c

Reference yield: 43.0%

(3S,6R,7S,8S)-11-((2R,3S)-3-((S,E)-2-amino-3-methyl-4-(2-methylthiazol-4-yl)but-3-enyl)-2-methyloxiran-2-yl)-3,7-dihydroxy-4,4,6,8-tetramethyl-5-oxoundecanoic acid (219990-25-7) → ixabepilone (219989-84-1)

Guidance literature:

With diphenyl-phosphinic acid; sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 4 ℃; for 24h;

DOI:10.1021/ja001899n

Reference yield: 40.0%

(3S,6R,7S,8S,12R,13S,15S)-15-amino-12,13-epoxy-4,4,6,8,12,16-hexamethyl-3,7-dihydroxy-17-(2-methyl-4-thiazolyl)-5-oxo-16-heptadecenoic acid → ixabepilone (219989-84-1)

Guidance literature:

With diphenyl phosphoryl azide; sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 0 - 4 ℃; for 24h; Inert atmosphere;

upstream raw materials:

[4S-[4R*,7S*,8R*,9R*,15R*(E)]]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-1-aza-13(Z)-cyclohexadecene-2,6-dione

(3S,6R,7S,8S)-11-((2R,3S)-3-((S,E)-2-amino-3-methyl-4-(2-methylthiazol-4-yl)but-3-enyl)-2-methyloxiran-2-yl)-3,7-dihydroxy-4,4,6,8-tetramethyl-5-oxoundecanoic acid

(Z)-(6R,7S,8S)-3-Methoxy-4,4,6,8-tetramethyl-5-oxo-7-(2,2,2-trichloro-ethoxycarbonyloxy)-undeca-2,10-dienoic acid tert-butyl ester

(5R)-5-hydroxy-2-iodo-6-methyl-7-(2-methylthiazol-4-yl)-2,6-heptadiene

Refernces

• 1、 -. "PROCESS FOR THE PREPARATION OF (1S,3S,7S,10R,11S,12S,16R)-7,11-DIHYDROXY-8,8,10,12,16-PENTAMETHYL-3-[(1E)-1-METHYL-2-(2-METHYL-4-THIAZOLYL)ETHENYL]-17-OXA-4-AZABICYCLO[14.1.0]HEPTADECANE-5,9-DIONE AND INTERMEDIATES THEREOF". Page/Page column 60. . Retrieved 2015/06/25.
• 2、 -. "PROCESS FOR PREPARATION OF IXABEPILONE AND INTERMEDIATES USEFUL IN SAID PROCESS.". Page/Page column 11. . Retrieved 2013/11/19.