Bosutinib

Base Information

• Chemical Name: Bosutinib
• CAS No.: 380843-75-4
• Molecular Formula: C26H29Cl2N5O3
• Molecular Weight: 530.454
• Hs Code.: 29335990
• European Community (EC) Number: 700-455-1
• UNII: 5018V4AEZ0
• DSSTox Substance ID: DTXSID10861568
• Nikkaji Number: J1.678.415J
• Wikipedia: Bosutinib
• Wikidata: Q894611
• NCI Thesaurus Code: C60809
• RXCUI: 1307619
• Pharos Ligand ID: ZLQR6LZVF9RB
• Metabolomics Workbench ID: 56170
• ChEMBL ID: CHEMBL288441
• Mol file: 380843-75-4.mol

Synonyms:bosutinib;SKI-606;SKI606

Chemical Property of Bosutinib

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 9.15E-17mmHg at 25°C
• Melting Point: 116-120 °C
• Refractive Index: 1.651
• Boiling Point: 649.7 °C at 760 mmHg
• PKA: 7.63±0.10(Predicted)
• Flash Point: 346.7 °C
• PSA: 82.88000
• Density: 1.36 g/cm³
• LogP: 5.13918
• Storage Temp.: room temp
• Solubility.: DMSO: ≥15mg/mL
• XLogP3: 5.4
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 9
• Exact Mass: 529.1647452
• Heavy Atom Count: 36
• Complexity: 734

Purity/Quality:

99.0% MIN ^*data from raw suppliers

Bosutinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36
• Safety Statements: 26

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CN1CCN(CC1)CCCOC2=C(C=C3C(=C2)N=CC(=C3NC4=CC(=C(C=C4Cl)Cl)OC)C#N)OC
• Recent ClinicalTrials: A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP
• Recent EU Clinical Trials: A patient guided dose reduction strategy of tyrosine kinase inhibitors in chronic myeloid leukaemia: a prospective, multi-centre, non-randomised non-inferiority study.
• Recent NIPH Clinical Trials: Phase 1 Dose Escalation Study of Bosutinib in Patients with Amyotrophic Lateral Sclerosis (ALS)
• Description: In September 2012, the US FDA approved bosutinib (also referred to as SKI-607) for the treatment of relapsed or refractory chronicmyeloid leukemia (CML) for patients with resistance or intolerance to prior therapy. The National Cancer Institute estimates that in 2012, 5430 men and women were diagnosed with CML and 610 died of CML. First and second-line therapies for the treatment of CML include imatinib, dasatinib, and nilotinib. Bosutinib, which was initially identified as a Src inhibitor, was later found to be a dual inhibitor of Bcr–Abl (IC50=1.4 nM) and Src family kinases (IC50=3.5 nM). Bosutinib inhibits 16 of 18 imatinib-resistant forms of Bcr–Abl expressed in murine myeloid cell lines. In preclinical in vivo studies, bosutinib at 15 mg/kg administered orally for 5 days caused regression of K562 CML tumors in nude mice and in BaF3 tumors expressing wild type or different imatinib-resistant Bcr–Abl mutants at varying doses. A manufacturing process for the synthesis of bosutinib monohydrate has been reported that employs a key three-component cyclization reaction involving an aniline, a cyanoacetamide intermediate, and triethyl orthoformate followed by cyclization using phosphorous oxytrichloride and an optimized hydration procedure.
• Uses: A novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells. peripheral vasolidator increases cerebral blood flow, potential therapeutic for Altzheimer’s disease, cognitive impairment and dementia Bosutinib (SKI-606) is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM, respectively.
• Clinical Use: Protein kinase inhibitor: Treatment of Philadelphia chromosome-positive chronic myelogenous leukaemia resistant or intolerant to prior therapy
• Drug interactions: Potentially hazardous interactions with other drugs Analgesics: possibly increased risk of ventricular arrhythmias with methadone. Anti-arrhythmics: possibly increased risk of ventricular arrhythmias with amiodarone and disopyramide; concentration possibly increased by dronedarone - avoid or consider reducing dose of bosutinib. Antibacterials: concentration possibly increased by ciprofloxacin, clarithromycin, erythromycin and telithromycin - avoid or consider reducing dose of bosutinib; possibly increased risk of ventricular arrhythmias with moxifloxacin; concentration reduced by rifampicin and possibly rifabutin - avoid. Antidepressants: concentration possibly reduced by St John’s wort - avoid. Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin, phenobarbital, phenytoin and primidone - avoid. Antifungals: concentration increased by ketoconazole and possibly by fluconazole, itraconazole, posaconazole and voriconazole - avoid or consider reducing dose of bosutinib. Antimalarials: possibly increased risk of ventricular arrhythmias with chloroquine and hydroxychloroquine. Antipsychotics: possibly increased risk of ventricular arrhythmias with haloperidol; avoid with clozapine, increased risk of agranulocytosis. Antivirals: concentration possibly increased by atazanavir, boceprevir, darunavir, fosamprenavir, indinavir, ritonavir, saquinavir and telaprevir - avoid or consider reducing dose of bosutinib; concentration possibly reduced by efavirenz and etravirine - avoid. Aprepitant: concentration possibly increased - avoid or consider reducing dose of bosutinib. Beta-blockers: possibly increased risk of ventricular arrhythmias with sotalol. Bosentan: concentration of bosutinib possibly reduced - avoid. Calcium channel blockers: concentration possibly increased by diltiazem or verapamil - avoid or consider reducing dose of bosutinib. Cytotoxics: concentration possibly increased by imatinib - avoid or consider reducing dose of bosutinib. Domperidone: avoid concomitant use, risk of ventricular arrhythmias. Fosaprepitant: concentration possibly increased by fosaprepitant - avoid or consider reducing dose of bosutinib Grapefruit juice: concentration possibly increased by grapefruit juice - avoid or consider reducing dose of bosutinib. Modafinil: concentration of bosutinib possibly reduced - avoid.

Technology Process of Bosutinib

There total 48 articles about Bosutinib 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: 99.4%

bosutinib benzoate → bosutinib (380843-75-4)

Guidance literature:

With 1-methyl-pyrrolidin-2-one; sodium hydrogencarbonate; In water; at 0 - 30 ℃; for 3h; Temperature; Inert atmosphere;

Reference yield: 88.6%

7-[3-(4-methylpiperazin-1-yl)propoxy]-6-methoxy-4-chloro-quinoline-3-carbonitrile (492444-39-0) + 2,4-dichloro-5-methoxyaniline (98446-49-2) → bosutinib (380843-75-4)

Guidance literature:

With potassium carbonate; In N,N-dimethyl-formamide; at 110 - 115 ℃; for 5h;

Reference yield: 83.5%

C26H31Cl2N5O4 → bosutinib (380843-75-4)

Guidance literature:

With sodium acetate; trichlorophosphate; In acetonitrile; at 65 - 70 ℃; for 6h; Reagent/catalyst; Solvent; Temperature; Inert atmosphere;

upstream raw materials:

1-methyl-piperazine

7-(3-chloropropoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile

3-(4-methyl-1-piperazinyl)-1-propanol

4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile

Downstream raw materials:

bosutinib monohydrate

4-((2,4-dichloro-5-methoxyphenyl)-amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)-propoxy)-3-quinoline-carbonitrile isopropanol solvate

4-((2,4-dichloro-5-methoxyphenyl)-amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)-propoxy)-3-quinoline-carbonitrile methanol solvate

C₃₃H₄₀Cl₂F₂N₈O₃

Refernces

• 1、 -. "Method for preparing bosutinib intermediate". Paragraph 0082. . Retrieved 2020/09/20.
• 2、 -. "Preparation method of disubstituted 4-chloroquinoline-3-carbonitrile derivative and preparation method of bosutinib". Paragraph 0102-0106. . Retrieved 2019/10/01.