Design of a Serotonin 4 Receptor Radiotracer with Decreased Lipophilicity for Single Photon Emission Computed Tomography
European Journal of Medicinal Chemistry 94 (2015) 386e396 Contents lists available at ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech Original article Design of a serotonin 4 receptor radiotracer with decreased lipophilicity for single photon emission computed tomography Nathalie Fresneau a,Noe Dumas b, Benjamin B. Tournier b, Christine Fossey c, Celine Ballandonne c,Aurelien Lesnard c, Philippe Millet b, Yves Charnay b, * * Thomas Cailly c, Jean-Philippe Bouillon a, ,Fred eric Fabis c, a Normandie Univ., COBRA, UMR 6014 et FR 3038, Univ. Rouen, INSA Rouen, CNRS, 1 Rue Tesniere, F-76821 Mont-Saint-Aignan Cedex, France b Hopitaux^ Universitaires de Geneve, Departement de Sante Mentale et de Psychiatrie, Service de Psychiatrie Generale, Unite des Biomarqueurs de Vulnerabilite, Chemin du Petit-Bel-Air, 2, CH-1225 Geneve, Switzerland c Normandie Univ., Universite de Caen Basse-Normandie, CERMN (EA 4258, FR CNRS 3038 INC3M, SF 4206 ICORE), UFR des Sciences Pharmaceutiques, Bd Becquerel, F-14032 Caen, France article info abstract Article history: With the aim to develop a suitable radiotracer for the brain imaging of the serotonin 4 receptor subtype Received 3 June 2014 (5-HT4R) using single photon emission computed tomography (SPECT), we synthesized and evaluated a Received in revised form library of di- and triazaphenanthridines with lipophilicity values which were in the range expected to 5 March 2015 favour brain penetration, and which demonstrated specific binding to the target of interest. Adding Accepted 6 March 2015 additional nitrogen atoms to previously described phenanthridine ligands exhibiting a high unspecific Available online 9 March 2015 binding, we were able to design a radioiodinated compound [125I]14.
[Show full text]