2. Academic Validation
  3. Discovery of MK-3168: A PET Tracer for Imaging Brain Fatty Acid Amide Hydrolase

Discovery of MK-3168: A PET Tracer for Imaging Brain Fatty Acid Amide Hydrolase

  • ACS Med Chem Lett. 2013 Apr 20;4(6):509-13. doi: 10.1021/ml4000996.
Ping Liu 1,  Terence G Hamill 2,  Marc Chioda 1,  Harry Chobanian 1,  Selena Fung 1,  Yan Guo 1,  Linda Chang 1,  Raman Bakshi 1,  Qingmei Hong 1,  James Dellureficio 1,  Linus S Lin 1,  Catherine Abbadie 1,  Jessica Alexander 1,  Hong Jin 1,  Suzanne Mandala 1,  Lin-Lin Shiao 1,  Wenping Li 2,  Sandra Sanabria 2,  David Williams 2,  Zhizhen Zeng 2,  Richard Hajdu 1,  Nina Jochnowitz 1,  Mark Rosenbach 1,  Bindhu Karanam 1,  Maria Madeira 1,  Gino Salituro 1,  Joyce Powell 1,  Ling Xu 1,  Jenna L Terebetski 1,  Joseph F Leone 1,  Patricia Miller 2,  Jacquelynn Cook 2,  Marie Holahan 2,  Aniket Joshi 2,  Stacey O'Malley 2,  Mona Purcell 2,  Diane Posavec 2,  Tsing-Bau Chen 2,  Kerry Riffel 2,  Mangay Williams 2,  Richard Hargreaves 2,  Kathleen A Sullivan 1,  Ravi P Nargund 1,  Robert J DeVita 1
Affiliations

Affiliations

  • 1 Departments of Medicinal Chemistry, Immunology, Pharmacology, Preclinical DMPK, Basic Pharmaceutical Sciences, and Process Research, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
  • 2 Department of Imaging Research, Merck Research Laboratories , West Point, Pennsylvania 19486, United States.
PMID: 24900701 DOI: 10.1021/ml4000996
Abstract

We report herein the discovery of a fatty acid amide hydrolase (FAAH) positron emission tomography (PET) tracer. Starting from a pyrazole lead, medicinal chemistry efforts directed toward reducing lipophilicity led to the synthesis of a series of imidazole analogues. Compound 6 was chosen for further profiling due to its appropriate physical chemical properties and excellent FAAH inhibition potency across species. [(11)C]-6 (MK-3168) exhibited good brain uptake and FAAH-specific signal in rhesus monkeys and is a suitable PET tracer for imaging FAAH in the brain.

Keywords

FAAH; Fatty acid amide hydrolase; PET tracer; biomarker; carbon-11; positron emission tomography; target engagement.

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