title: 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.
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.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Linus S
authors.initials: LS
authors.lastname: Lin
authors.forename: Terence G
authors.initials: TG
authors.lastname: Hamill
authors.forename: James P
authors.initials: JP
authors.lastname: Jewell
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lanza
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Gibson
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Krause
authors.forename: Christine
authors.initials: C
authors.lastname: Ryan
authors.forename: Waisi
authors.initials: W
authors.lastname: Eng
authors.forename: Sandra
authors.initials: S
authors.lastname: Sanabria
authors.forename: Xinchun
authors.initials: X
authors.lastname: Tong
authors.forename: Junying
authors.initials: J
authors.lastname: Wang
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Levorse
authors.forename: Karen A
authors.initials: KA
authors.lastname: Owens
authors.forename: Tung M
authors.initials: TM
authors.lastname: Fong
authors.forename: Chun-Pyn
authors.initials: CP
authors.lastname: Shen
authors.forename: Julie
authors.initials: J
authors.lastname: Lao
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Wenji
authors.initials: W
authors.lastname: Yin
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Payack
authors.forename: Shawn A
authors.initials: SA
authors.lastname: Springfield
authors.forename: Richard
authors.initials: R
authors.lastname: Hargreaves
authors.forename: H Donald
authors.initials: HD
authors.lastname: Burns
authors.forename: Mark T
authors.initials: MT
authors.lastname: Goulet
authors.forename: William K
authors.initials: WK
authors.lastname: Hagmann
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005462:Fluorine Radioisotopes; D006801:Humans; D008253:Macaca mulatta; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D005462:Fluorine Radioisotopes; C523403:N-(2-(3-cyanophenyl)-3-(4-(2-fluoroethoxy)phenyl)-1-methylpropyl)-2-methyl-2-((5-methylpyridin-2-yl)oxy)propanamide; D011725:Pyridines; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1; D011994:Recombinant Proteins