- Potent and selective tariquidar bioisosters as potential PET radiotracers for imaging P-gp
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Compounds 8a-d have been designed as bioisosters of tariquidar for imaging P-gp expression and density by PET. The results displayed that compounds 8b and 8d could be considered potential P-gp/BCRP ligands suitable as 11C and 18F radiotracers, respectively.
- Contino, Marialessandra,Zinzi, Laura,Perrone, Maria Grazia,Leopoldo, Marcello,Berardi, Francesco,Perrone, Roberto,Colabufo, Nicola Antonio
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supporting information
p. 1370 - 1374
(2013/03/14)
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- Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: Application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer
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Arylphenylpyrrolidinylmethylphenoxybenzamides were found to have high affinity and selectivity for κ opioid receptors. On the basis of receptor binding assays in Chinese hamster ovary (CHO) cells expressing cloned human opioid receptors, (S)-3-fluoro-4-(4-((2-(3-fluorophenyl)pyrrolidin-1-yl)methyl) phenoxy)benzamide (25) had a Ki = 0.565 nM for κ opioid receptor binding while having a Ki = 35.8 nM for μ opioid receptors and a Ki = 211 nM for δ opioid receptor binding. Compound 25 was also a potent antagonist of κ opioid receptors when tested in vitro using a [35S]-guanosine 5′O-[3-thiotriphosphate] ([35S]GTP-γ-S) functional assay in CHO cells expressing cloned human opioid receptors. Compounds were also evaluated for potential use as receptor occupancy tracers. Tracer evaluation was done in vivo, using liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods, precluding the need for radiolabeling. (S)-3-Chloro-4-(4-((2-(pyridine-3-yl)pyrrolidin-1-yl)methyl) phenoxy)benzamide (18) was found to have favorable properties for a tracer for receptor occupancy, including good specific versus nonspecific binding and good brain uptake.
- Mitch, Charles H.,Quimby, Steven J.,Diaz, Nuria,Pedregal, Concepcion,De La Torre, Marta G.,Jimenez, Alma,Shi, Qing,Canada, Emily J.,Kahl, Steven D.,Statnick, Michael A.,McKinzie, David L.,Benesh, Dana R.,Rash, Karen S.,Barth, Vanessa N.
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p. 8000 - 8012
(2012/01/19)
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- DIARYL ETHERS AS OPIOID RECEPTOR ANTAGONIST
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A compound of the formula (I) wherein the variables X1 to X10, R1 to R7 including R3', E, v, y, z, A and B are as described, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixtures thereof, useful for the treatment, prevention or amelioration of obesity and Related Diseases is disclosed.
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Page/Page column 186-187
(2008/06/13)
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