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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.
Liu P,
Lin LS,
Hamill TG,
Jewell JP,
Lanza TJ Jr,
Gibson RE,
Krause SM,
Ryan C,
Eng W,
Sanabria S,
Tong X,
Wang J,
Levorse DA,
Owens KA,
Fong TM,
Shen CP,
Lao J,
Kumar S,
Yin W,
Payack JF,
Springfield SA,
Hargreaves R,
Burns HD,
Goulet MT,
Hagmann WK.
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.
PMID: 17608398 [PubMed - indexed for MEDLINE]
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Cited by 2 PubMed Central articles
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Evaluation of [11C]PipISB and [18F]PipISB in monkey as candidate radioligands for imaging brain cannabinoid type-1 receptors in vivo.
Finnema SJ, Donohue SR, Zoghbi SS, Brown AK, Gulyás B, Innis RB, Halldin C, Pike VW.
Synapse. 2009 Jan; 63(1):22-30.
[Synapse. 2009]
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Synthesis, ex vivo evaluation, and radiolabeling of potent 1,5-diphenylpyrrolidin-2-one cannabinoid subtype-1 receptor ligands as candidates for in vivo imaging.
Donohue SR, Krushinski JH, Pike VW, Chernet E, Phebus L, Chesterfield AK, Felder CC, Halldin C, Schaus JM.
J Med Chem. 2008 Sep 25; 51(18):5833-42.
[J Med Chem. 2008]