Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 and Fluorine-18 (N-Fluoroalkyl) Labeled 2β-Carbomethoxy-3β-(4'-(3-furyl)phenyl)tropanes and -nortropanes:  Candidate Radioligands for in Vivo Imaging of the Serotonin Transporter with Positron Emission Tomography

• Published in: Journal of medicinal chemistry Vol. 48; no. 22; pp. 7080 - 7083
• Main Authors: Stehouwer, Jeffrey S, Plisson, Christophe, Jarkas, Nachwa, Zeng, Fanxing, Voll, Ronald J, Williams, Larry, Martarello, Laurent, Votaw, John R, Tamagnan, Gilles, Goodman, Mark M
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 03.11.2005; Amer Chemical Soc
• Subjects: Biological and medical sciences; Chemistry, Medicinal; Contrast media. Radiopharmaceuticals; Life Sciences & Biomedicine; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; ACID; AFFINITY; ANALOGS; ESTERS; CHEMISTRY; COCAINE; RECEPTOR; DOPAMINE TRANSPORTER; BETA-CIT; TROPANE; Intravenous administration; Fluorine 18; Nitrogen heterocycle; Ligand; Furan derivatives; Monkey; Central nervous system; Carbon Isotopes; Molecular interaction; Encephalon; Ester; Tissue; Structure activity relation; Membrane transport; Primates; Carbon 11; Bicyclic compound; Chemical synthesis; Carrier protein; Fluorine Isotopes; Radiolabelling; Serotonin; In vitro; Tropane derivatives; In vivo; Vertebrata; Biological fixation; Mammalia; Animal; Distribution; Affinity; Fluorine Organic compounds; Pharmacokinetics; Positron emission tomography
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm0504095

2β-Carbomethoxy-3β-(4‘-(3-furyl)phenyl)nortropane (1) was synthesized along with the N-methyl (2), N-fluoroethyl (3), N-fluoropropyl (4), and N-fluorobutyl (5) derivatives. The binding affinity for each compound to the human serotonin, dopamine, and norepinephrine transporters was determined using transfected HEK-293 cells. Radiolabeling and microPET brain imaging studies were performed with [11C]1, [11C]2, and [18F]3 to determine their utility as in vivo imaging agents.