title: Synthesis and evaluation of potent and selective human V1a receptor antagonists as potential ligands for PET or SPECT imaging.
abstract: SRX246 is a potent, highly selective human vasopressin V1a antagonist that crosses the blood-brain barrier in rats. CNS penetration makes SRX246 an ideal candidate for potential radiolabeling and use in visualization and characterization of the role of the V1a receptor in multiple stress-related disorders. Before radiolabeling studies, cold reference analogs of SRX246 were prepared. This study describes the synthesis and in vitro screening for human V1a receptor binding and permeability of fluoro, iodo, and methyl reference compounds for SRX246 and the preparation of a tin precursor. For each compound, the potential utility of corresponding radiolabeled analogs for PET and SPECT imaging is discussed.
authors.affiliation: Dept. of Chemistry, Lehigh University, Bethlehem, PA 18015, USA.
authors.forename: Karine
authors.initials: K
authors.lastname: Fabio
authors.forename: Christophe
authors.initials: C
authors.lastname: Guillon
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Lacey
authors.forename: Shi-fang
authors.initials: SF
authors.lastname: Lu
authors.forename: Ned D
authors.initials: ND
authors.lastname: Heindel
authors.forename: Craig F
authors.initials: CF
authors.lastname: Ferris
authors.forename: Michael
authors.initials: M
authors.lastname: Placzek
authors.forename: Graham
authors.initials: G
authors.lastname: Jones
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Brownstein
authors.forename: Neal G
authors.initials: NG
authors.lastname: Simon
mesh_terms: D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000378:metabolism; D001384:Azetidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D008024:Ligands; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D011868:Radioisotopes / Q000737:chemistry* / Q000494:pharmacology*; D017483:Receptors, Vasopressin / Q000032:analysis; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001384:Azetidines; D008024:Ligands; D011868:Radioisotopes; D017483:Receptors, Vasopressin; C584649:SRX246; D001127:Arginine Vasopressin