Document Report Card

ID: ALA2385021

Journal: ACS Med Chem Lett

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

Authors: Liu P, Hamill TG, Chioda M, Chobanian H, Fung S, Guo Y, Chang L, Bakshi R, Hong Q, Dellureficio J, Lin LS, Abbadie C, Alexander J, Jin H, Mandala S, Shiao LL, Li W, Sanabria S, Williams D, Zeng Z, Hajdu R, Jochnowitz N, Rosenbach M, Karanam B, Madeira M, Salituro G, Powell J, Xu L, Terebetski JL, Leone JF, Miller P, Cook J, Holahan M, Joshi A, O'Malley S, Purcell M, Posavec D, Chen TB, Riffel K, Williams M, Hargreaves R, Sullivan KA, Nargund RP, DeVita RJ.

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.

CiteXplore: 24900701

DOI: 10.1021/ml4000996