220565-63-9Relevant academic research and scientific papers
Investigations into the potential role of metabolites on the anti-leukemic activity of imatinib, nilotinib and midostaurin
Manley, Paul W.
, p. 561 - 570 (2019/09/03)
The efficacy and side-effects of drugs do not just reflect the biochemical and pharmacodynamic properties of the parent compound, but often comprise of cooperative effects between the properties of the parent and active metabolites. Metabolites of imatinib, nilotinib and midostaurin have been synthesised and evaluated in assays to compare their properties as protein kinase inhibitors with the parent drugs. The N-desmethylmetabolite of imatinib is substantially less active than imatinib as a BCR-ABL1 kinase inhibitor, thus providing an explanation as to why patients producing high levels of this metabolite show a relatively low response rate in chronic myeloid leukaemia (CML) treatment. The hydroxymethylphenyl and N-oxide metabolites of imatinib and nilotinib are only weakly active as BCR-ABL1 inhibitors and are unlikely to play a role in the efficacy of either drug in CML. The 3-(R)-HO-metabolite of midostaurin shows appreciable accumulation following chronic drug administration and, in addition to mutant forms of FLT3, potently inhibits the PDPK1 and VEGFR2 kinases (IC50 values 100 nM), suggesting that it might contribute to drug efficacy in acute myeloid leukaemia patients. The case studies discussed here provide further examples of how the synthesis and characterisation of metabolites can make important contributions to understanding the clinical efficacy of drugs.
Fukuyama Cross-Coupling Approach to Isoprekinamycin: Discovery of the Highly Active and Bench-Stable Palladium Precatalyst POxAP
Tang, Shuang-Qi,Bricard, Jacques,Schmitt, Martine,Bihel, Frédéric
supporting information, p. 844 - 848 (2019/01/30)
An efficient and user-friendly palladium(II) precatalyst, POxAP (post-oxidative-addition precatalyst), was identified for use in Fukuyama cross-coupling reactions. Suitable for storage under air, the POxAP precatalyst allowed reaction between thioesters and organozinc reagents with turnover numbers of ～90000. A series of 23 ketones were obtained with yields ranging from 53 to 99%. As proof of efficacy, an alternative approach was developed for the synthesis of a key precursor of the natural product isoprekinamycin.
Cobalt-Catalyzed Formation of 2-Pyridylzinc Reagents and Their Subsequent Coupling
Linke, Stephanie,Manolikakès, Sofia M.,Auffrant, Audrey,Gosmini, Corinne
, p. 2595 - 2600 (2018/06/08)
The preparation of pyridylzinc compounds from the corresponding pyridyl halides using a cobalt catalyst is described. The complex employed features a polydentate N-heterocyclic ligand and allows the reaction to be carried out in the absence of pyridine as
A method for preparing abiraterone acetate (by machine translation)
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Paragraph 0030; 0031, (2017/02/09)
The invention relates to a method for preparing abiraterone acetate, the method is to dehydrogenation epandrosterone as raw materials, with hydrazine hydrate, iodine response, to obtain 17-iodo-androst -5,16-diene -3 β-ol, then the under the catalysis of palladium benzene phosphine base43 with 3-pyridine zinc halide occurs arab League bit dragon Negishi coupling reaction, the final with acetyl chloride or acetic anhydride esterification, to obtain the target product abiraterone acetate. (by machine translation)
Novel process for preparing Imatinib
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Page/Page column 7, (2008/06/13)
A novel process is disclosed for producing Imatinib, using the precursor 2-chloro-4-(3-pyridyl)-pyrimidine, thus improving Imatinib preparation via an alternative synthetic route, avoiding the use of the toxic reagent cyanamide.
