SYNTHESIS AND INVITRO CHARACTERIZATION OF FLUORINATED U-50488 ANALOGS FOR PET STUDIES OF KAPPA-OPIOID RECEPTORS

The κ type-specific opioid, U-50488 7, was selected as a parent compound for the synthesis of an 18F-labeled analog suitable for imaging κ 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 κ 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. © 1990.