Imatinib Mesylate: An Optimization in its Synthesis

Boechat, Núbia; Bastos, Mônica M.; Duarte, S. L.; Costa, Jorge; Mafra, João C. M.; Daniel, L. C. C.

doi:10.5935/1984-6835.20130023

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…)pyrimidin-2amine (5) was obtained from the aromatic nucleophilic substitution reaction of intermediate PAPP via the formation of a diazonium salt with 84% yield, which was characterized, and its data agreed with those in the literature [29]. The carbonyl nucleophilic substitution reaction between intermediate PAPP and chloroacetyl chloride (7) generated N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)chloroacetamide (8) in 81% yield, and its characterization data were in accordance with the literature [30].…”

Section: N-(5-azido-2-methylphenyl)-4-(pyridin-3-ylsupporting

confidence: 72%

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

Pimentel

Hoelz

Canzian

et al. 2021

Beilstein J. Org. Chem.

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The enzyme tyrosine kinase BCR-Abl-1 is the main molecular target in the treatment of chronic myeloid leukemia and can be competitively inhibited by tyrosine kinase inhibitors such as imatinib. New potential competitive inhibitors were synthesized using the (phenylamino)pyrimidine-pyridine (PAPP) group as a pharmacophoric fragment, and these compounds were biologically evaluated. The synthesis of twelve new compounds was performed in three steps and assisted by microwave irradiation in a 1,3-dipolar cycloaddition to obtain 1,2,3-triazole derivatives substituted on carbon C-4 of the triazole nucleus. All compounds were evaluated for their inhibitory activities against a chronic myeloid leukemia cell line (K562) that expresses the enzyme tyrosine kinase BCR-Abl-1 and against healthy cells (WSS-1) to observe their selectivity. Three compounds showed promising results, with IC50 values between 1.0 and 7.3 μM, and were subjected to molecular docking studies. The results suggest that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One compound showed the greatest interaction affinity for BCR-Abl-1 in the docking studies.

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Section: N-(5-azido-2-methylphenyl)-4-(pyridin-3-ylsupporting

confidence: 72%

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

Pimentel

Hoelz

Canzian

et al. 2021

Beilstein J. Org. Chem.

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“…Imatinib, which was only released for use in 2001, is considered a milestone in the history of current medicine, as it is one of the main representants of the first generation of kinase inhibitors (KIs). Since it was developed, it has been possible to offer chronic myeloid leukemia patients a more effective therapy with fewer adverse events [ 32 ].…”

Section: Recent Prospects Into Clinical Investigationsmentioning

confidence: 99%

Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution

Pessoa

Machado

Silva

et al. 2022

IJMS

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The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients’ prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones’ survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host’s immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.

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