380843-75-4

Basic information

• Product Name: Bosutinib
• Synonyms: 3-Quinolinecarbonitrile, 4-[(2,4-dichloro-5-Methoxyphenyl)aMino]-6-Methoxy-7-[3-(4-Methyl-1-piperazinyl)propoxy]-;Bosutinib(TINIBS );4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile Bosutinib (SKI-606);WAY-173606;Bosulif(bosutinib);SKI-606;BOSUTINIB;Bosutinib for research
• CAS NO: 380843-75-4
• Molecular Formula: C₂₆H₂₉Cl₂N₅O₃
• Molecular Weight: 530.45
• EINECS: 1308068-626-2
• Product Categories: Intermediates & Fine Chemicals;Pfizer compounds;Pharmaceuticals;API;Aromatics Compounds;Aromatics;Heterocycles;Inhibitors;Bosutinib ada@tuskwei.com whatsapp;8618031153937
• Mol File: 380843-75-4.mol
• Article Data: 21

Chemical Properties

• Melting Point: 116-120 ºC
• Boiling Point: 649.7 °C at 760 mmHg
• Flash Point: 346.7 °C
• Appearance: off-white to light brown/
• Density: 1.36
• Vapor Pressure: 9.15E-17mmHg at 25°C
• Refractive Index: 1.651
• Storage Temp.: room temp
• Solubility: DMSO: ≥15mg/mL
• PKA: 7.63±0.10(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: Bosutinib(CAS DataBase Reference)
• NIST Chemistry Reference: Bosutinib(380843-75-4)
• EPA Substance Registry System: Bosutinib(380843-75-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 380843-75-4(Hazardous Substances Data)

Usage

Description

Bosutinib, also known as SKI-607, is a dual Src/Abl inhibitor that was approved by the US FDA in September 2012 for the treatment of relapsed or refractory chronic myeloid leukemia (CML) in patients with resistance or intolerance to prior therapy. It was initially identified as a Src inhibitor but was later found to inhibit both Bcr-Abl and Src family kinases. Bosutinib has shown efficacy in preclinical in vivo studies and has a manufacturing process for the synthesis of its monohydrate form.

Uses

Used in Oncology:
Bosutinib is used as an anticancer agent for the treatment of relapsed or refractory chronic myeloid leukemia (CML) in patients with resistance or intolerance to prior therapy. It inhibits 16 of 18 imatinib-resistant forms of Bcr-Abl expressed in murine myeloid cell lines and has shown regression of CML tumors in preclinical in vivo studies.
Used in Cancer Cell Research:
Bosutinib is used as a novel Src kinase inhibitor to suppress the migration and invasion of human breast cancer cells, indicating its potential use in cancer cell research and development.
Used in Neurology:
Bosutinib is used as a peripheral vasolidator to increase cerebral blood flow, making it a potential therapeutic agent for Alzheimer's disease, cognitive impairment, and dementia.
Used in Pharmaceutical Research:
Bosutinib (SKI-606) is a novel, dual Src/Abl inhibitor with IC50 values of 1.2 nM and 1 nM, respectively, making it a valuable compound for pharmaceutical research and development.

Originator

Wyeth (United States)

Biochem/physiol Actions

Bosutinib (SKI-606) is an orally active; dual Src/Abl tyrosine kinase inhibitor with potent antiproliferative activity. It does not appear to inhibit c-Kit and PDGRF, which are thought to be the cause of numerous side effects in anticancer treatment with some other tyrosine kinase inhibitors.

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.

Metabolism

Mainly hepatically metabolised. The major circulating metabolites identified in plasma are oxydechlorinated (M2) bosutinib (19% of parent exposure) and N-desmethylated (M5) bosutinib (25% of parent exposure), with bosutinib N-oxide (M6) as a minor circulating metabolite. All the metabolites are inactive. Excretion is mainly via the faeces.

References

Golas et al. (2003), SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice; Cancer Res., 63 375 Remsing Rix et al. (2009), Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells; Leukemia, 23 477 Redaelli et al. (2009), Activity of bosutinib, Dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants; J. Clin. Oncol., 27 469 MacDonald et al. (2018), Src family kinase inhibitor bosutinib enhances retinoic acid-induced differentiation of HL-60 leukemia cells; Leuk. Lymphoma, 59 2941 Vultur et al. (2008), SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells; Mol. Cancer Ther., 7 1185

InChI:InChI=1/C26H29Cl2N5O3/c1-32-6-8-33(9-7-32)5-4-10-36-25-13-21-18(11-24(25)35-3)26(17(15-29)16-30-21)31-22-14-23(34-2)20(28)12-19(22)27/h11-14,16H,4-10H2,1-3H3,(H,30,31)

Upstream product

• 109-01-3 1-methyl-piperazine 
• 380844-49-5 7-(3-chloropropoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile 
• 5317-33-9 3-(4-methyl-1-piperazinyl)-1-propanol 
• 622369-46-4 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile 
• 366-99-4 3-fluoro-4-methoxyaniline 
• 98446-49-2 2,4-dichloro-5-methoxyaniline 
• 622369-40-8 4-chloro-6-methoxy-7-fluoro-quinoline-3-carbonitrile 
• 622369-38-4 7-fluoro-6-methoxy-4-oxo-1,4-dihydro-3-quinolinecarbonitrile 
• 214470-68-5 7-(3-chloro-propoxy)-4-chloro-6-methoxy-quinoline-3-carbonitrile 
• 92878-95-0 1-(2-methoxy-5-nitrophenoxy)-3-chloropropane 
• 846023-54-9 1-[3-(2-methoxy-5-nitrophenoxy)propyl]-4-methylpiperazine 
• 3943-74-6 4-hydroxy-3-methoxybenzoic acid methyl ester 
• 111627-40-8 methyl 4-(3-chloropropoxy)-3-methoxybenzoate 
• 846023-24-3 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)acetamide 

Downstream Products

• 918639-08-4 bosutinib monohydrate 
• 918639-09-5 4-((2,4-dichloro-5-methoxyphenyl)-amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)-propoxy)-3-quinoline-carbonitrile isopropanol solvate 
• 918639-10-8 4-((2,4-dichloro-5-methoxyphenyl)-amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)-propoxy)-3-quinoline-carbonitrile methanol solvate 
• 1450912-84-1 C₃₃H₄₀Cl₂F₂N₈O₃ 

Relevant articles and documents

A robust, streamlined approach to bosutinib monohydrate

This article describes a systematic approach used to streamline the process for the isolation of bosutinib monohydrate, a promiscuous solvate former. A thorough understanding of the complex solid form landscape was garnered, and this knowledge was used to

Method for preparing bosutinib intermediate

The invention provides a method for preparing a bosutinib intermediate. The method comprises the following steps: A, adding SM-1, 1-bromo-3-chloropropane and an acid-binding agent into a reaction solvent, controlling the temperature until the reaction is

Bosutinib purification method

The invention provides a bosutinib purification method. The method includes the steps of firstly, dissolving crude bosutinib in an acetonitrile-water mixed solvent; secondly, optionally performing activated carbon decoloring, and filtering to obtain filtrate; thirdly, cooling, crystallizing, filtering, and drying to obtain purified bosutinib. The bosutinib purification method has the advantages that the method can replace a column chromatography purification method or a preparative chromatography purification method to remove impurities, which is hard to purify by a conventional crystallizingmethod, in the crude bosutinib, and the method is low in solvent use amount, simple in process, high in purification yield and product purity and beneficial to industrial production.