190728-24-6Relevant articles and documents
One-step synthesis of [18F]cabozantinib for use in positron emission tomography imaging of c-Met
Lien, Vegard Torp,Klaveness, Jo,Olberg, Dag Erlend
, p. 11 - 17 (2018)
Cabozantinib is an FDA-approved kinase inhibitor for the treatment of medullary thyroid cancer and advanced renal cell carcinoma, which exerts its therapeutic effect by inhibiting, among others, the tyrosine kinase c-Met. Noninvasive imaging techniques are becoming increasingly important clinically to ensure drug efficacy, staging, monitoring, and patient stratification. PET isotope labelled tyrosine kinase inhibitors have, for the same reason, potential as PET tracers for imaging of various cancers. On the basis of cabozantinib, we synthesized the novel boronic acid pinacol ester 4 as a labelling precursor, where the boronic ester moiety replaces the fluorine native to this kinase inhibitor. By this, we wanted to explore whether recently developed Cu-mediated fluorination methods are adaptable to more complex substrates and thereby provide easy access to [18F]cabozantinib directly. Hydrolysis was implemented before preparative purification due to challenges with on-column hydrolysis of the precursor 4, and [18F]cabozantinib was obtained in ≥99% radiochemical purity and in 2.8?±?0.05% (n?=?4) isolated decay corrected yield in a synthesis time of 90?minutes. The molar activity of representative batches was determined to be 17?±?8?GBq/μmol.
Synthesis and antiproliferative evaluation of novel N-arylquinolones
Lien, Vegard Torp,Olberg, Dag Erlend,Hagelin, Gunnar,Klaveness, Jo
, p. 1947 - 1957 (2019)
Abstract: Novel N-aryl-substituted quinolones were evaluated for antiproliferative activity. The chemical modifications were inspired by previously reported cytotoxic agents with structural similarities. Dimethylated anilines displayed the most potent effect in the renal cancer cell line Caki-1 and the breast cancer cell line MDA-MB-231, with GI50 values down to 24 μM. Further evaluation in the NCI60 cell lines revealed growth inhibition up to 50%, with the strongest effect observed in renal and lung cancer cell lines. In silico ADMET evaluation indicated favorable characteristics for both gastrointestinal and CNS uptake. The potential toxic electrophilic α,β-unsaturated carbonyl functionalities were shown to be inert to ethanethiol. Graphic abstract: [Figure not available: see fulltext.]
Method of Treating Cancer and Bone Cancer Pain
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, (2020/08/25)
This invention is directed to the treatment of cancer, particularly lung cancer, breast cancer, melanoma, renal cell carcinoma, thyroid cancer that has metastasized to the bone. The invention is also directed to a method for treating bone cancer pain in a
COMPOUNDS FOR THE TREATMENT OF KINASE-DEPENDENT DISORDERS
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Paragraph 00245; 00267-00268, (2020/08/13)
The present invention relates to compounds that modulate cellular activities such as proliferation, differentiation, programmed cell death, migration, and chemoinvasion, by modulating protein kinase enzymatic activity, and compositions thereof, and methods of using such compounds.