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N-Desmethyl Imatinib is a major active metabolite of imatinib, an anticancer agent that selectively targets tyrosine kinases, including Bcr-ABL, platelet-derived growth factor receptor (PDGFR), and KIT. It is formed when imatinib undergoes demethylation by the cytochrome P450 (CYP) isomer CYP3A4 and possesses the same in vitro potency at Bcr-ABL kinase as imatinib.
Used in Oncology:
N-Desmethyl Imatinib is used as an anticancer agent for the treatment of chronic myelogenous leukemia (CML) and certain forms of acute lymphoblastic leukemia (ALL). It is a metabolite of Gleevec, a tyrosine kinase inhibitor highly specific for BCR-ABL, the enzyme associated with these diseases.
Used in Antibacterial Applications:
N-Desmethyl Imatinib is used as an aminoglycoside antibiotic, similar to gentamycin, for its toxic effects on bacterial, yeast, higher plant, and mammalian cells, as well as protozoans and helminthes.
Used in Neurology:
N-Desmethyl Imatinib is used as an anti-epileptic agent for the treatment of epilepsy and related seizure disorders.

404844-02-6

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404844-02-6 Usage

Check Digit Verification of cas no

The CAS Registry Mumber 404844-02-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 4,0,4,8,4 and 4 respectively; the second part has 2 digits, 0 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 404844-02:
(8*4)+(7*0)+(6*4)+(5*8)+(4*4)+(3*4)+(2*0)+(1*2)=126
126 % 10 = 6
So 404844-02-6 is a valid CAS Registry Number.
InChI:InChI=1/C28H29N7O/c1-20-4-9-24(17-26(20)34-28-31-12-10-25(33-28)23-3-2-11-30-18-23)32-27(36)22-7-5-21(6-8-22)19-35-15-13-29-14-16-35/h2-12,17-18,29H,13-16,19H2,1H3,(H,32,36)(H,31,33,34)

404844-02-6Relevant articles and documents

Haptens, antigens and antibodies of imatinib and N-demethylated imatinib and application thereof

-

, (2021/06/09)

The invention relates to the technical field of immunological detection, and particularly discloses haptens, antigens and antibodies of imatinib and N-demethylated imatinib and application of the haptens, the antigens and the antibodies, the structure of

Global PROTAC Toolbox for Degrading BCR-ABL Overcomes Drug-Resistant Mutants and Adverse Effects

Yang, Yiqing,Gao, Hongying,Sun, Xiuyun,Sun, Yonghui,Qiu, Yueping,Weng, Qinjie,Rao, Yu

, p. 8567 - 8583 (2020/09/16)

The BCR-ABL fusion oncoprotein causes chronic myeloid leukemia or acute lymphoblastic leukemia in Ph+ patients because the ABL kinase is constitutively activated. However, current clinical treatment with ABL inhibitors is seriously limited by drug resistance and adverse effects. Although the emerging proteolysis-Targeting chimeras (PROTACs) have been introduced to degrade BCR-ABL, most of them showed limited activity and could not overcome the common drug-resistant mutants, especially for T315I mutant. Herein, we systematically designed a set of unique PROTACs by globally targeting all the three binding sites of BCR-ABL, including dasatinib-, ponatinib-, and asciminib-based PROTACs. Our ponatinib-based PROTACs showed practical activity as dasatinib-based PROTACs, while no reported ponatinib-based PROTACs could degrade BCR-ABL before. As a proof of concept, some additional dasatinib-based PROTACs were then designed to degrade T315I mutant too. We provided a global PROTAC toolbox for degrading both wild-Type and T315I-mutated BCR-ABL from each binding site. More importantly, these PROTACs showed better selectivity and less adverse effects than the inhibitors, indicating that PROTACs had great potential for overcoming clinical drug resistance and safety issues.

Development of Gleevec Analogues for Reducing Production of β-Amyloid Peptides through Shifting β-Cleavage of Amyloid Precursor Proteins

Sun, Weilin,Netzer, William J.,Sinha, Anjana,Gindinova, Katherina,Chang, Emily,Sinha, Subhash C.

supporting information, p. 3122 - 3134 (2019/04/01)

Imatinib mesylate, 1a, inhibits production of β-amyloid (Aβ) peptides both in cells and in animal models. It reduces both the β-secretase and γ-secretase cleavages of the amyloid precursor protein (APP) and mediates a synergistic effect, when combined with a β-secretase inhibitor, BACE IV. Toward developing more potent brain-permeable leads, we have synthesized and evaluated over 75 1a-analogues. Several compounds, including 2a-b and 3a-c, inhibited production of Aβ peptides with improved activity in cells. These compounds affected β-secretase cleavage of APP similarly to 1a. Compound 2a significantly reduced production of the Aβ42 peptide, when administered (100 mg/kg, twice daily by oral gavage) to 5 months old female mice for 5 days. A combination of compound 2a with BACE IV also reduced Aβ levels in cells, more than the additive effect of the two compounds. These results open a new avenue for developing treatments for Alzheimer's disease using 1a-analogues.

A novel structure of the kinase inhibitors

-

, (2018/06/07)

The invention provides compounds of a novel kinase inhibitor as shown in the formula (I) or pharmaceutically acceptable salts, solvates, esters, acids, metabolites, combination drugs or prodrugs thereof. The compounds independently combines with at least

Enantioselective synthesis of α-secondary and α-tertiary piperazin-2- Ones and piperazines by catalytic asymmetric allylic alkylation

Korch, Katerina M.,Eidamshaus, Christian,Behenna, Douglas C.,Stoltz, Brian M.,Nam, Sangkil,Horne, David

, p. 179 - 183 (2015/02/05)

The asymmetric palladium-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2- ones allows the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogues. The introduction of these chiral tertiary piperazines resulted in imatinib analogues which exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts.

The kinetic deuterium isotope effect as applied to metabolic deactivation of imatinib to the des-methyl metabolite, CGP74588

Manley, Paul W.,Blasco, Francesca,Mestan, Jürgen,Aichholz, Reiner

, p. 3231 - 3239 (2013/07/11)

There has recently been a burgeoning interest in impeding drug metabolism by replacing hydrogen atoms with deuterium to invoke a kinetic isotope effect. Imatinib, a front-line therapy for both chronic myeloid leukemia and of gastrointestinal stromal tumours, is often substantially metabolised via N-demethylation to the significantly less active CGP74588. Since deuterium-carbon bonds are stronger than hydrogen-carbon bonds, we hypothesised that the N-trideuteromethyl analogue of imatinib might be subject to a reduced metabolic turnover as compared to imatinib and lead to different pharmacokinetic properties, and hence improved efficacy, in vivo. Consequently, we investigated whether the N-trideuteromethyl analogue would maintain target inhibition and show a reduced propensity for N-demethylation in in vitro assays with liver microsomes and following oral administration to rats. The N-trideuteromethyl compound exhibited similar activity as a tyrosine kinase inhibitor as imatinib and similar efficacy as an antiproliferative in cellular assays. In comparison to imatinib, the trideuterated analogue also showed reduced N-demethylation upon incubation with both rat and human liver microsomes, consistent with a deuterium isotope effect. However, the reduced in vitro metabolism did not translate into increased exposure of the N-trideuteromethyl analogue following intravenous administration of the compound to rats and no significant difference was observed for the formation of the N-desmethyl metabolite from either parent drug.

N-phenyl-2-pyrimidine-amine derivatives

-

, (2008/06/13)

The invention relates to N-phenyl-2-pyrimidine-amine derivatives of formula (I) wherein the substituents are defined as indicated in the description, to processes for the preparation thereof, to medicaments comprising those compounds, and the use thereof

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