- Synthesis and biological evaluation of potential 5-HT7 receptor PET radiotracers
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Brain serotonin 7 receptor (5-HT7) is involved in several mood disorders and drug candidates targeting this subtype are currently in development. Positron emission tomography (PET) is a molecular imaging modality offering great promise for accelerating the process from preclinical discovery to clinical phases. As no PET radiopharmaceutical has yet been used successfully to study the 5-HT7 receptor in vivo, our objective is to develop the first 5-HT7 fluorine-18 labeled radiotracer. Four structural analogs of SB269970, a specific 5-HT7 receptor antagonist, divided in FP3 series and FPMP series were synthesized. Their antagonist effects were investigated by cellular functional assay. Nitro-precursors of these analogs were radiolabeled via a [18F-]nucleophilic substitution and in vitro autoradiographies were performed in rat brain. Chemical and radiochemical purities of fluorine radiotracers were >99% with specific activities in 40-129 GBq/μmole range. The four derivates presented antagonism potencies toward 5-HT7 receptors (pKB) between 7.8 and 8.8. The four PET radiotracers had suitable characteristic for 5-HT7 receptor probing in vitro even if the FP3 series seemed to be more specific for this receptor. These results encourage us to pursue in vivo studies.
- Andries, Julien,Lemoine, Laetitia,Le Bars, Didier,Zimmer, Luc,Billard, Thierry
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scheme or table
p. 3455 - 3461
(2011/08/03)
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- Improved protocol for asymmetric, intramolecular heteroatom Michael addition using organocatalysis: Enantioselective syntheses of homoproline, pelletierine, and homopipecolic acid
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(Chemical Equation Presented) An improved protocol for the construction of enantioenriched pyrrolidine, indoline, and piperidine rings using an organocatalyzed, intramolecular heteroatom Michael addition is described. Application to the enantioselective synthesis of homoproline, homopipecolic acid, and pelletierine has been accomplished.
- Carlson, Erik C.,Rathbone, Lauren K.,Yang, Hua,Collett, Nathan D.,Carter, Rich G.
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p. 5155 - 5158
(2008/09/21)
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- Asymetric Electrophilic α-Amidoalkylation 4: Generation and Trapping Reactions of Chiral N-Acylpyrrolidiniumions
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The pyrrole derivatives 1, 6, and 10 react in the presence of TiCl4 with the silyl enol ether 3 to form α-substituted pyrrolidine amides stereoselectively. 6 and 10 (after HCl-addition =>11) react even at -78 deg C, the reaction of 10 exceeds that of 6 in yield and stereoselctivity.
- Wanner, Klaus Th.,Hoefner, Georg
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