Discovery of MK-3168: A PET Tracer for Imaging Brain Fatty Acid Amide Hydrolase
ACS Medicinal Chemistry Letters2013Vol. 4(6), pp. 509–513
Citations Over TimeTop 10% of 2013 papers
Ping Liu, Terence G. Hamill, Marc Chioda, Harry R. Chobanian, Selena Fung, Yan Guo, Linda Chang, Raman K. Bakshi, Qingmei Hong, James Dellureficio, Linus S. Lin, Catherine Abbadie, Jessica P. Alexander, Hongjian Jin, Suzanne Mandala, Lin‐Lin Shiao, Wenping Li, Sandra Sanabria, David L. Williams, Zhizhen Zeng, Richard Hajdu, Nina Jochnowitz, Mark Rosenbach, Bindhu V. Karanam, Maria Madeira, Gino Salituro, Joyce Powell, Ling Xu, Jenna L. Terebetski, Joseph F. Leone, Patricia Miller, Jacquelynn J. Cook, Marie A. Holahan, Aniket Joshi, Stacey O’Malley, Mona Purcell, Diane Posavec, Tsing‐Bau Chen, Kerry Riffel, Mangay Williams, Richard Hargreaves, Kathleen A. Sullivan, Ravi P. Nargund, Robert J. DeVita
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.
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