title: Synthesis and in vitro characterization of fluorinated U-50488 analogs for PET studies of kappa opioid receptors.
abstract: The kappa type-specific opioid, U-50488 7, was selected as a parent compound for the synthesis of an 18F-labeled analog suitable for imaging kappa opioid receptors with positron emission tomography (PET). The N-normethyl U-50488 analog 5 was synthesized as a precursor for fluoroalkylation, but it was found to be too unreactive for this technique. Instead, the desired N-fluoroalkyl analogs 10, 11 were made by alkylation of trans-diaminocyclohexane precursor 4 with subsequent acylation. The in vitro binding affinity (Ki) of these fluorinated ligands for the kappa opioid receptor is reduced two orders of magnitude relative to U-50488. The decrease in binding affinity caused by the fluoroalkyl substitution renders these new analogs inappropriate for PET studies.
authors.affiliation: Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: P L
authors.initials: PL
authors.lastname: Chesis
authors.forename: M J
authors.initials: MJ
authors.lastname: Welch
mesh_terms: D005461:Fluorine; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D011759:Pyrrolidines / Q000138:chemical synthesis*; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D014055:Tomography, Emission-Computed
chemical_list: D005462:Fluorine Radioisotopes; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D005461:Fluorine