220127-57-1 Usage
Description
Imatinib mesylate, also known as Gleevec or Glivec, is a methanesulfonate salt that is the monomesylate salt of imatinib. It is an orally bioavailable tyrosine kinase inhibitor, highly specific for BCR-ABL, the enzyme associated with chronic myelogenous leukemia (CML) and certain forms of acute lymphoblastic leukemia (ALL). Imatinib is the first of a new class of anticancer drugs that are specifically designed to target the molecular pathways involved in the development of disease. It is a competitive inhibitor of the tyrosine kinase as well as Abl, Kit, and the PDGFR kinases, binding to the ATP-binding site of the target kinase and preventing the transfer of phosphate from ATP to the tyrosine residues of various substrates, consequently blocking the proliferation of the leukemic cells.
Uses
Used in Pharmaceutical Industry:
Imatinib mesylate is used as an anticancer agent for the treatment of chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST) that express Kit. It is effective in blast crisis, accelerated phase, or chronic phase after interferon-alpha failure. Imatinib has advantages over IFN-alpha, such as reduced toxicity, more rapid hematological response, higher rate of cytogenic response, and oral administration.
Used in Antifungal Applications:
Imatinib mesylate is used as an echinocandin antifungal, active against infections with Aspergillus and Candida. It inhibits cell wall synthesis, providing an alternative treatment option for patients with fungal infections.
Used in Research and Development:
Imatinib mesylate is used as a multi-target inhibitor of v-Abl, c-Kit, and PDGFR in research and development for the study of various oncogenic events and the development of targeted therapies for cancer treatment.
Used in Drug Metabolism Studies:
Imatinib mesylate is used in studies related to drug metabolism, as it is primarily metabolized by the CYP3A4 enzyme system. Understanding the interaction between Imatinib and the CYP3A4 system can help in predicting potential drug-drug interactions and modifying the patient's exposure to the drug.
a small-molecule inhibitor
Imatinib mesylate (also called Gleevec) is a small-molecule inhibitor of the fusion protein Bcr-Abl, the causal agent in chronic myelogenous leukemia.
As an inhibitor of PDGFR, imatinib mesylate appears to have utility in the treatment of a variety of dermatological diseases. Imatinib has been reported to be an effective treatment for FIP1L1-PDGFRalpha+ mast cell disease, hypereosinophilic syndrome, and dermatofibrosarcoma protuberans.
Originator
Novartis (Switzerland)
Biochem/physiol Actions
Imatinib mesylate is a tyrosine kinase inhibitor with antineoplastic activity. Imatinib is a potent inhibitor of the Bcr-Abl kinase encoded by the bcr-abl oncogene as well as receptor tyrosine kinases encoded by c-kit and platelet-derived growth factor receptor (PDGFR) oncogenes. Imatinib mesylate inhibition of Bcr-Abl tyrosine kinase created by the Philadelphia chromosome abnormality found in CML decreases proliferation and enhances apoptosis in leukemias CML and ALL. Inhibition of c-kit tyrosine activity inhibits mast-cell and cellular proliferation in those diseases overexpressing c-kit such as gastrointestinal stromal tumor (GIST).
References
1) Buchdunger, et al.(1996) Inhibition of the Abl Protein-Tyrosine Kinase in Vitro and in Vivo by a 2-Phenylpyrimidine Derivative; Cancer Res. 56 100
2) Heinrich et al (2000) Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 96 925
3) Morioka et al. (2016) Effect of Collagen Type 1 or Human Fibronectin on Imatinib Cytotoxicity in Oral Squamous Cell Carcinoma; Pharmacology and Pharmacy, 7 255 [Focus Biomolecules Citation]
4) Hazekawa et al. (2017) Assessment of cytotoxicity of imatinib for oral squamous cell carcinoma by a real-time cell analysis system; E. J. Bio., 13 56 [ Focus Biomolecules Citation]
Check Digit Verification of cas no
The CAS Registry Mumber 220127-57-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,2,0,1,2 and 7 respectively; the second part has 2 digits, 5 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 220127-57:
(8*2)+(7*2)+(6*0)+(5*1)+(4*2)+(3*7)+(2*5)+(1*7)=81
81 % 10 = 1
So 220127-57-1 is a valid CAS Registry Number.
InChI:InChI=1/C29H31N7O.CH4O3S/c1-21-5-10-25(18-27(21)34-29-31-13-11-26(33-29)24-4-3-12-30-19-24)32-28(37)23-8-6-22(7-9-23)20-36-16-14-35(2)15-17-36;1-5(2,3)4/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34);1H3,(H,2,3,4)
220127-57-1Relevant articles and documents
A PROCESS FOR PREPARATION OF IMATINIB BY USING VILSMEIER REAGENT
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Page/Page column 15, (2021/07/17)
The present invention relates to a process of preparation of Imatinib, wherein said process comprises one or more steps of converting benzoic acid intermediate (formula 8) into Imatinib in presence of Vilsmeier reagent preferably under basic condition. Vilsmeier reagent in the present invention is prepared by reaction of chlorinating agent and catalyst. In a preferred embodiment Chlorinating agent is thionyl chloride and catalyst is dimethyl formamide.
Preparation method of imatinib mesylate
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Paragraph 0010, (2020/12/05)
The invention discloses a preparation method of imatinib mesylate. The method comprises the following steps: chlorinating imatinib acid[4-(4-methylpiperazine-1-ylmethyl)benzoic acid dihydrochloride] with thionyl chloride to generate an imatinib mesylate intermediate I; condensing the imatinib mesylate intermediate I with imatinib amine [N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine] toobtain an imatinib mesylate intermediate II, and finally salifying the imatinib mesylate intermediate II with methanesulfonic acid to obtain imatinib mesylate. According to the invention, the raw materials imatinib acid and imatinib amine used in the method are common medical intermediates, other raw materials and reagents used in the process are convenient and easy to obtain, the reaction process and post-treatment operation are simple and convenient, the yield is high, and the production cost is effectively reduced through process optimization.
Purification method of imatinib
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Paragraph 0090; 0091; 0092; 0093, (2017/10/28)
The invention relates to a purification method of imatinib. The method has the characteristics of simple technique, high safety, environment friendliness, low cost and favorable repeatability, and can implement industrialized large-scale production. By using the method, the content of the genotoxic impurity N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-aminopyrimidine in the imatinib can be lowered to 2ppm or below according to the pharmacopoeia requirement, and the product purity is up to 99.8% or above.
