title: Synthesis and biological evaluation of halogenated naphthyridone carboxamides as potential ligands for in vivo imaging studies of substance P receptors.
abstract: With the aim of developing new radioligands for in vivo studies of substance P receptors using positron emission tomography or single photon emission computed tomography, 2- and 3-halo naphthyridone-6-carboxamide derivatives were synthesized. Their affinities toward the target receptors were evaluated on CHO cells and compared to the unsubstituted analogue EP 00652218 (IC(50) = 100 nM +/- 20). The IC(50) value was not altered in the case of 2-chloro compound 1 (IC(50) = 100 nM +/- 15) and only slightly reduced for the 2-fluoro and -iodo analogues 6 and 8 (IC(50) = 500 nM +/- 80). A drastic reduction in binding (IC(50) > 1000 nM) was observed for the halogenated compounds 2-5, 7, and 9.
authors.affiliation: Groupe de Développements Méthodologiques en Tomographie par Emission de Positons, UMR CEA, Université de Caen-Basse Normandie, Centre Cyceron, 15 Boulevard Henri Becquerel, 14070 Caen Cedex, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bagot-Guéret
authors.forename: Marie-Delphine
authors.initials: MD
authors.lastname: Le Bas
authors.forename: Sylvie
authors.initials: S
authors.lastname: Tymciu
authors.forename: Mircea
authors.initials: M
authors.lastname: Darabantu
authors.forename: Patrick
authors.initials: P
authors.lastname: Emond
authors.forename: Denis
authors.initials: D
authors.lastname: Guilloteau
authors.forename: Marie Claire
authors.initials: MC
authors.lastname: Lasne
authors.forename: Anne
authors.initials: A
authors.lastname: Wijkhuisen
authors.forename: Louisa
authors.initials: L
authors.lastname: Barré
authors.forename: Cécile
authors.initials: C
authors.lastname: Perrio
mesh_terms: D000818:Animals; D001711:Biotransformation; D016466:CHO Cells; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006219:Halogens / Q000138:chemical synthesis / Q000378:metabolism*; D006868:Hydrolysis; D008024:Ligands; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000378:metabolism*; D011869:Radioligand Assay / Q000379:methods; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D006219:Halogens; D008024:Ligands; D009287:Naphthyridines; D018040:Receptors, Neurokinin-1