Discovery of [ 11 C]MK-8056: A Selective PET Imaging Agent for the Study of mGluR 2 Negative Allosteric Modulators.
James J PerkinsPaul McQuadeChristopher J BungardTracy L DiamondLiza T GantertAnthony L GotterBarbara HanneyIvory D HillsDanielle M HurzyAniket JoshiJonathan T KernKelly-Ann S SchlegelJesse J ManikowskiZhaoyang MengJulie A O'BrienAnthony J RoeckerSean M SmithJason M UslanerEric HostetlerRobert S MeissnerPublished in: ACS medicinal chemistry letters (2023)
Modification of potent, selective metabotropic glutamate receptor 2 negative allosteric modulator (mGluR 2 NAM) led to a series of analogues with excellent binding affinity, lipophilicity, and suitable physicochemical properties for a PET tracer with convenient chemical handles for incorporation of a 11 C or 18 F radiolabel. [ 11 C]MK-8056 was synthesized and evaluated in vivo and demonstrated appropriate affinity, selectivity, and physicochemical properties to be used as a positron emission tomography tracer for mGluR 2 .