1. Synthesis and evaluation of potent and selective human V1a receptor antagonists as potential ligands for PET or SPECT imaging
- Author
-
Karine Fabio, Neal G. Simon, Graham B. Jones, Christophe Guillon, Ned D. Heindel, Michael J. Brownstein, Shi-fang Lu, Michael S. Placzek, Carl Jeffrey Lacey, and Craig F. Ferris
- Subjects
Receptors, Vasopressin ,SRX246 ,Clinical Biochemistry ,Pharmaceutical Science ,Plasma protein binding ,Pharmacology ,Blood–brain barrier ,Ligands ,Biochemistry ,digestive system ,Article ,Cell Line ,chemistry.chemical_compound ,Spect imaging ,Drug Discovery ,medicine ,Humans ,Receptor ,Molecular Biology ,Radioisotopes ,Tomography, Emission-Computed, Single-Photon ,Organic Chemistry ,Antagonist ,Antidiuretic Hormone Receptor Antagonists ,In vitro ,Arginine Vasopressin ,medicine.anatomical_structure ,chemistry ,Blood-Brain Barrier ,Positron-Emission Tomography ,Molecular Medicine ,Azetidines ,Protein Binding - 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.
- Published
- 2011