3区 · 医学
Article
作者: Bakshi, Raman ; Xu, Ling ; Madeira, Maria ; Hamill, Terence G ; Nargund, Ravi P ; Holahan, Marie ; 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 ; Riffel, Kerry ; Shiao, Lin-Lin ; Sullivan, Kathleen A ; Miller, Patricia ; DeVita, Robert J ; Terebetski, Jenna L ; Karanam, Bindhu ; Sanabria, Sandra ; Purcell, Mona ; Salituro, Gino ; Fung, Selena ; Chang, Linda ; Chen, Tsing-Bau ; Rosenbach, Mark ; Jin, Hong ; Chobanian, Harry ; Abbadie, Catherine ; Powell, Joyce ; Hargreaves, Richard ; Jochnowitz, Nina ; Mandala, Suzanne ; Li, Wenping ; Hong, Qingmei ; Williams, David ; Liu, Ping ; Guo, Yan ; Dellureficio, James
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.