Discovery of N-{(1S,2S)-2-(3-Cyanophenyl)- 3-[4-(2-[(18)F]fluoroethoxy)phenyl]-1-methylpropyl}- 2-methyl-2-[(5-methylpyridin-2-yl)oxy]propanamide, a Cannabinoid-1 Receptor Positron Emission Tomography Tracer Suitable for Clinical Use.
Journal of medicinal chemistry 2007 Jul 3; 50(15):3427-30
Liu P P, Lin L S, Hamill T G, Jewell J P, Lanza T J, Gibson R E,
Departments of Medicinal Chemistry, Metabolic Disorders, Drug Metabolism, and Process Research, Merc
The discovery of a structurally distinct cannabinoid-1 receptor (CB1R) positron emission tomography tracer is described. Starting from an acyclic amide CB1R inverse agonist (1) as the lead compound, an efficient route to introduce 18F to the molecule was developed. Further optimization focused on reducing the lipophilicity and increasing the CB1R affinity. These efforts led to the identification of [18F]-16 that exhibited good brain uptake and an excellent signal-to-noise ratio in rhesus monkeys.