1. Academic Validation
  2. 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.
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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