title: Synthesis and biological evaluation of novel fluoro and iodo quinoline carboxamides as potential ligands of NK-3 receptors for in vivo imaging studies.
abstract: In order to develop radioligands of human NK-3 receptor (hNK-3r) for imaging studies by positron emission tomography (PET) or single photon emission computed tomography (SPECT), a new series of fluoro- and iodo-quinoline carboxamides were synthesized and evaluated in a target receptor binding assay. Compared to the unsubstituted parent compound SB 223 412 (Ki=27 nM +/- 9), affinity was not altered for the analogues 1c and 2c bearing a fluorine in position 8 (Ki approximately 24-27 nM), and was only slightly reduced for compounds 1b, 2b, 1e and 2e fluorinated or iodinated at the position 7 (Ki approximately 49-67 nM). A drastic reduction in binding (Ki > 115 nM) was observed for all other halogenated compounds 1a, 2a, 1d, 2d, 1f and 2f.
authors.affiliation: Groupe de Développements Méthodologiques en Tomographie par Emission de Positons, UMR CEA, FRECNRS 2698, Université de Caen-Basse Normandie, Centre Cyceron, 15 Boulevard Henri Becquerel, 14070 Caen Cedex, France.
authors.forename: Idriss
authors.initials: I
authors.lastname: Bennacef
authors.forename: Sylvie
authors.initials: S
authors.lastname: Tymciu
authors.forename: Martine
authors.initials: M
authors.lastname: Dhilly
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Lasne
authors.forename: Danielle
authors.initials: D
authors.lastname: Debruyne
authors.forename: Cécile
authors.initials: C
authors.lastname: Perrio
authors.forename: Louisa
authors.initials: L
authors.lastname: Barré
mesh_terms: D005461:Fluorine / Q000737:chemistry; D007455:Iodine / Q000737:chemistry; D008024:Ligands; D049268:Positron-Emission Tomography; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism*; D018042:Receptors, Neurokinin-3 / Q000737:chemistry / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D008024:Ligands; D011804:Quinolines; D018042:Receptors, Neurokinin-3; C106716:SB 223412; D005461:Fluorine; D007455:Iodine