Q3 · MEDICINE
Article
Author: Bakshi, Raman ; Xu, Ling ; Madeira, Maria ; Hamill, Terence G ; Holahan, Marie ; Nargund, Ravi P ; Alexander, Jessica ; Williams, Mangay ; Zeng, Zhizhen ; Hajdu, Richard ; Cook, Jacquelynn ; Lin, Linus S ; Joshi, Aniket ; Chioda, Marc ; O'Malley, Stacey ; Posavec, Diane ; Leone, Joseph F ; Sullivan, Kathleen A ; Riffel, Kerry ; Shiao, Lin-Lin ; DeVita, Robert J ; Miller, Patricia ; Terebetski, Jenna L ; Karanam, Bindhu ; Sanabria, Sandra ; Salituro, Gino ; Purcell, Mona ; Fung, Selena ; Chang, Linda ; Rosenbach, Mark ; Chen, Tsing-Bau ; Jin, Hong ; Abbadie, Catherine ; Chobanian, Harry ; Powell, Joyce ; Hargreaves, Richard ; Jochnowitz, Nina ; Mandala, Suzanne ; Li, Wenping ; Williams, David ; Hong, Qingmei ; Liu, Ping ; Dellureficio, James ; Guo, Yan
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.