- Synthesis and evaluation of 2-pyridylbenzothiazole, 2-pyridylbenzoxazole and 2-pyridylbenzofuran derivatives as 11C-PET imaging agents for β-amyloid plaques
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The syntheses and SAR of new series of β-amyloid binding agents are reported. The effort to optimize signal-to-background ratios for these ligands are described. Compounds 8, 21 and 30 displayed desirable lipophilicity and pharmacokinetic properties. Compounds 8 and 21 were evaluated with in vitro autoradiographic studies and in vivo in APP/PS1 transgenic mice. It is shown that it was possible to increase the signal-to-background ratios compared to PIB 1, as demonstrated by compounds 8 and 21.
- Swahn, Britt-Marie,Wensbo, David,Sandell, Johan,Sohn, Daniel,Slivo, Can,Pyring, David,Malmstr?m, Jonas,Arzel, Erwan,Vallin, Michaela,Bergh, Margareta,Jeppsson, Fredrik,Johnson, Allan E.,Juréus, Anders,Neelissen, Jan,Svensson, Samuel
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- Synthesis and evaluation of three 18F-labeled aminophenylbenzothiazoles as amyloid imaging agents
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We have developed three fluorine-18 labeled 6-(methyl)amino-2-(4′- fluorophenyl)-1,3-benzothiazoles, which display high in vitro binding affinity for human amyloid β plaques (Ki ≤ 10 nM). The radiolabeled probes were synthesized by aromatic nucleophilic substitution of the corresponding nitro precursor with 18F-fluoride, followed by deprotection of the BOC group if required. Determination of the octanol/water partition coefficient, biodistribution studies in mice, and in vivo μPET studies in rats and a rhesus monkey showed that initial brain uptake was high and brain washout was fast in normal animals. Radiometabolites were quantified in plasma and brain of mice and in monkey plasma using HPLC. Of the tested compounds, [18F]2 (6-amino-2-(4′-[18F]fluorophenyl)- 1,3-benzothiazole) shows the most favorable brain kinetics in mice, rats, and a monkey. Its polar plasma radiometabolites do not cross the blood-brain barrier. The preliminary results strongly suggest that this new fluorinated compound is a promising candidate as a PET brain amyloid imaging agent. 2009 American Chemical Society.
- Serdons, Kim,Van Laere, Koen,Janssen, Peter,Kung, Hank F.,Bormans, Guy,Verbruggen, Alfons
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supporting information; experimental part
p. 7090 - 7102
(2010/07/20)
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- 2-Hydroxy-4,6-diamino-[1,3,5]triazines: A novel class of VEGF-R2 (KDR) tyrosine kinase inhibitors
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2-Hydroxy-4,6-diamino-[1,3,5]triazines are described which are a novel class of potent inhibitors of the VEGF-R2 (flk-1/KDR) tyrosine kinase. 4-(Benzothiazol-6-ylamino)-6-(benzyl-isopropyl-amino)-[1,3,5]triazin-2-ol (14d) exhibited low nanomolar potency i
- Baindur, Nand,Chadha, Naresh,Brandt, Benjamin M.,Asgari, Davoud,Patch, Raymond J.,Schalk-HiHi, Celine,Carver, Theodore E.,Petrounia, Ioanna P.,Baumann, Christian A.,Ott, Heidi,Manthey, Carl,Springer, Barry A.,Player, Mark R.
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p. 1717 - 1720
(2007/10/03)
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- Mesolimbic selective antipsychotic arylcarbamates
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4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidine has been linked to various arylcarbamates to obtain compounds having affinity for dopamine-D1 and -D2, serotonin 5HT(2A) and α1-adrenoceptors. When linkers with restricted flexibility are used, the biological activity is reduced indicating that a bended conformation is needed in this series of bioactive molecules. Compounds with a relatively low D2/5HT(2A) affinity ratio in receptor binding experiments and high affinity for the α1-adrenoceptors exhibit a pharmacological profile which suggests a preferential effect on the mesocorticolimbic dopaminergic system and an 'atypical' antipsychotic activity.
- Hansen, John Bondo,Fink-Jensen, Anders,Christensen, Birgitte V.,Gronvald, Frederick C.,Jeppesen, Lone,Mogensen, John P.,Nielsen, Erik B.,Scheideler, Mark A.,White, Francis J.,Zhang, Xu-Feng
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p. 839 - 858
(2007/10/03)
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