Discovery of N-{(1S,2S)-2-(3-cyanophenyl)- 3-[4-(2-[18F]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

  • J Med Chem. 2007 Jul 26;50(15):3427-30. doi: 10.1021/jm070131b.
Ping Liu ,  Linus S Lin ,  Terence G Hamill ,  James P Jewell ,  Thomas J Lanza Jr ,  Raymond E Gibson ,  Stephen M Krause ,  Christine Ryan ,  Waisi Eng ,  Sandra Sanabria ,  Xinchun Tong ,  Junying Wang ,  Dorothy A Levorse ,  Karen A Owens ,  Tung M Fong ,  Chun-Pyn Shen ,  Julie Lao ,  Sanjeev Kumar ,  Wenji Yin ,  Joseph F Payack ,  Shawn A Springfield ,  Richard Hargreaves ,  H Donald Burns ,  Mark T Goulet ,  William K Hagmann
PMID: 17608398 DOI: 10.1021/jm070131b
Abstract

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.