Discovery ofN-{(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
Journal of Medicinal Chemistry2007Vol. 50(15), pp. 3427–3430
Citations Over TimeTop 10% of 2007 papers
Ping Liu, Linus S. Lin, Terence G. Hamill, James P. Jewell, Thomas J. Lanza, Raymond E. Gibson, Stephen M. Krause, Christine Ryan, Waisi Eng, Sandra Sanabria, Xinchun Tong, Junying Wang, Dorothy Levorse, K. 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
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.
Related Papers
- → Agonist-induced modulation of inverse agonist efficacy at the beta 2-adrenergic receptor.(1996)92 cited
- → Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A2A Receptor(2021)40 cited
- Short-term inverse-agonist treatment induces reciprocal changes in delta-opioid agonist and inverse-agonist binding capacity.(2001)
- Characteristics of inverse agonist action(2005)
- [Inverse agonist: a novel discovery in receptor research].(1997)