| Literature DB >> 26077491 |
Christopher D Cox1, Eric D Hostetler2, Broc A Flores3, Jeffrey L Evelhoch2, Hong Fan2, Liza Gantert2, Marie Holahan2, Waisi Eng2, Aniket Joshi2, Georgia McGaughey4, Xiangjun Meng2, Mona Purcell2, Izzat T Raheem3, Kerry Riffel2, Youwei Yan5, John J Renger6, Sean M Smith6, Paul J Coleman3.
Abstract
Phosphodiesterase 10A (PDE10A) inhibition has recently been identified as a potential mechanism to treat multiple symptoms that manifest in schizophrenia. In order to facilitate preclinical development and support key proof-of-concept clinical trials of novel PDE10A inhibitors, it is critical to discover positron emission tomography (PET) tracers that enable plasma concentration/PDE10A occupancy relationships to be established across species with structurally diverse PDE10A inhibitors. In this Letter, we describe how a high-throughput screening hit was optimized to provide [(11)C]MK-8193 (8j), a PET tracer that supports the determination of plasma concentration/PDE10A occupancy relationships for structurally diverse series of PDE10A inhibitors in both rat and rhesus monkey.Entities:
Keywords: Huntington’s disease; Imaging; PDE10A; PET tracer; Phosphodiesterase 10A; Positron emission tomography; Schizophrenia
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Year: 2015 PMID： 26077491 DOI： 10.1016/j.bmcl.2015.05.080
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823