343788-51-2Relevant articles and documents
Rhenium(i) complexation-dissociation strategy for synthesising fluorine-18 labelled pyridine bidentate radiotracers
Ciancaleoni, Gianluca,Clegg, Jack K.,Fraser, Benjamin H.,Howard, James K.,Klenner, Mitchell A.,Massi, Massimiliano,Maynard-Casely, Helen E.,Pascali, Giancarlo,Zhang, Bo
, p. 8853 - 8865 (2020)
A novel fluorine-18 method employing rhenium(i) mediation is described herein. The method was found to afford moderate to high radiochemical yields of labelled rhenium(i) complexes. Subsequent thermal dissociation of the complexes enabled the radiosynthesis of fluorine-18 labelled pyridine bidentate structures which could not be radiofluorinated hitherto. This rhenium(i) complexation-dissociation strategy was further applied to the radiosynthesis of [18F]CABS13, an Alzheimer's disease imaging agent, alongside other 2,2′-bipyridine, 1,10-phenanthroline and 8-hydroxyquinoline labelled radiotracers. Computational modelling of the reaction mechanism suggests that the efficiency of rhenium(i) activation may be attributed to both an electron withdrawal effect by the metal center and the formation of an acyl fluoride intermediate which anchors the fluoride subsequent to nucleophilic addition.
SNAr Radiofluorination with in Situ Generated [18F]Tetramethylammonium Fluoride
Lee, So Jeong,Morales-Colón, María T.,Brooks, Allen F.,Wright, Jay S.,Makaravage, Katarina J.,Scott, Peter J. H.,Sanford, Melanie S.
, p. 14121 - 14130 (2021/09/28)
This report describes a method for the nucleophilic radiofluorination of (hetero)aryl chlorides, (hetero)aryl triflates, and nitroarenes using a combination of [18F]KF·K2.2.2 and Me4NHCO3 for the in situ formation of a strongly nucleophilic fluorinating reagent (proposed to be [18F]Me4NF). This method is applied to 24 substrates bearing diverse functional groups, and it generates [18F](hetero)aryl fluoride products in good to excellent radiochemical yields in the presence of ambient air/moisture. The reaction is applied to the preparation of 18F-labeled HQ-415 for potential (pre)clinical use.
Telescoping the Synthesis of the [18F]CABS13 Alzheimer's Disease Radiopharmaceutical via Flow Microfluidic Rhenium(I) Complexations
Evans, Brendan J.,Fraser, Benjamin H.,Klenner, Mitchell A.,Massi, Massimiliano,Moon, Vaughan,Pascali, Giancarlo
, p. 3554 - 3564 (2020/10/02)
The syntheses of rhenium(I) complexes were achieved under flow microfluidic conditions. The use of a single microreactor was applied towards complexation of the 6-chloro-2,2'-bipyridine diimine ligand, with ideal complexation conditions around 170 °C. Subsequent radiolabelling with [18F]fluoride was further achieved by flowing through a second heated microreactor, alongside a stream of dried radiofluorination media. Temperature modulation across both microreactors resulted in 23.6 % and 37.0 % radiochemical yield (RCY) of [18F]6-fluoro-2,2'-bipyridine and its associated [18F]tricarbonyl(2-fluoro-2,2'-bipyridine)rhenium(I) chloride complex, respectively. Translation of this set-up to the synthesis of the [18F]CABS13 Alzheimer's disease positron emission tomography (PET) imaging agent was achieved with the incorporation of a third microreactor to enable thermal control of the complexation, fluorination and decomplexation pathways. Optimal RCYs of 2.7 % and 1.9 % of [18F]CABS13 and its rhenium(I) complexation were achieved in-flow, respectively. However, discrepancies in the RCYs were found to arise from differences in the grade of anhydrous dimethyl sulfoxide (DMSO) employed in the continuous-flow reactions. Anhydrous DMSO from Sigma-Aldrich (≤ 99.9 %) in former experiments afforded higher yielders in comparison to replicate experiments employing anhydrous DMSO from Merck Millipore (≤ 99.7 %), thus demonstrating that control of the solvent grade is key to optimizing reaction RCYs.
PRMT5 INHIBITORS AND USES THEREOF
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, (2019/04/05)
Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
Synthesis and evaluation of radioiodinated 1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}piperidin-4-amine derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging
Effendi, Nurmaya,Ogawa, Kazuma,Mishiro, Kenji,Takarada, Takeshi,Yamada, Daisuke,Kitamura, Yoji,Shiba, Kazuhiro,Maeda, Takehiko,Odani, Akira
, p. 5576 - 5585 (2017/10/06)
Platelet-derived growth factor receptor β (PDGFRβ) is a transmembrane tyrosine kinase receptor and it is upregulated in various malignant tumors. Radiolabeled PDGFRβ inhibitors can be a convenient tool for the imaging of tumors overexpressing PDGFRβ. In this study, [125I]-1-{5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinoline-8-yl}piperidin-4-amine ([125I]IIQP) and [125I]-N-3-iodobenzoyl-1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}-piperidin-4-amine ([125I]IB-IQP) were designed and synthesized, and their potential as PDGFRβ imaging agents was evaluated. In cellular uptake experiments, [125I]IIQP and [125I]IB-IQP showed higher uptake by PDGFRβ-positive cells than by PDGFRβ-negative cells, and the uptake in PDGFRβ-positive cells was inhibited by co-culture with PDGFRβ ligands. The biodistribution of both radiotracers in normal mice exhibited hepatobiliary excretion as the main route. In mice inoculated with BxPC3-luc (PDGFRβ-positive), the tumor uptake of radioactivity at 1 h after the injection of [125I]IIQP was significantly higher than that after the injection of [125I]IB-IQP. These results indicated that [125I]IIQP can be a suitable PDGFRβ imaging agent. However, further modification of its structure will be required to obtain a more appropriate PDGFRβ-targeted imaging agent with a higher signal/noise ratio.
Discovery of a novel class of imidazo[1,2-a ]pyridines with potent PDGFR activity and oral bioavailability
Hicken, Erik J.,Marmsater, Fred P.,Munson, Mark C.,Schlachter, Stephen T.,Robinson, John E.,Allen, Shelley,Burgess, Laurence E.,Delisle, Robert Kirk,Rizzi, James P.,Topalov, George T.,Zhao, Qian,Hicks, Julie M.,Kallan, Nicholas C.,Tarlton, Eugene,Allen, Andrew,Callejo, Michele,Cox, April,Rana, Sumeet,Klopfenstein, Nathalie,Woessner, Richard,Lyssikatos, Joseph P.
, p. 78 - 83 (2014/02/14)
The in silico construction of a PDGFRβ kinase homology model and ensuing medicinal chemistry guided by molecular modeling, led to the identification of potent, small molecule inhibitors of PDGFR. Subsequent exploration of structure-activity relationships
PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF
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, (2014/07/08)
Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.
IMIDAZO[1,2-A]PYRIDINE COMPOUNDS AS RECEPTOR TYROSINE KINASE INHIBITORS
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, (2008/12/04)
Compounds of Formula I: in which A, B, R1, R1a, R2, R3, R4, R5 R6, R7 and R8 have the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment of diseases mediated by class 3 and class 5 receptor tyrosine kinases. Particular compounds of this invention have also been found to be inhibitors of Pim-1.
IMIDAZO[1,2-A]PYRIDINE COMPOUNDS AS RECEPTOR TYROSINE KINASE INHIBITORS
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, (2008/12/04)
Compounds of Formula (I) in which A, B, R1, R1a, R2, R3, R4, R5, R6, R7 and R8 have the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment of diseases mediated by class 3 and class 5 receptor tyrosine kinases. Particular compounds of this invention have also been found to be inhibitors of Pim-1
NOVEL COMPOUNDS HAVING AN ANTI-BACTERIAL ACTIVITY
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Page/Page column 143, (2010/10/20)
The present invention describes novel anti-bacterial compounds of formula (I). These compounds are, amongst others, of interest as inhibitors of DNA gyrase.
