FAAH inhibitor 1 (Synonyms: Benzothiazole analog 3)

FAAH inhibitor 1 is a potent fatty acid amide hydrolase (FAAH) inhibitor with an IC50 of 18±8 nM.IC50 Value: 18±8 nM [1]Target: FAAHTime-dependent preincubation study of FAAH inhibitor 1 was consistent with it being a reversible inhibitor. Activity-based protein-profiling (ABPP) evaluation of FAAH inhibitors 1 in rat tissues revealed that it had exceptional selectivity and no off-target activity with respect to other serine hydrolases. Molecular shape overlay of FAAH inhibitor 1 with a known FAAH inhibitor indicated that these compounds might act as transitionstate analogues, forming putative hydrogen bonds with catalytic residues and mimicking the charge distribution of the tetrahedral transition state. FAAH inhibitors 1 was exclusively specific against FAAH in rat brain and had no missing protein bands in all the other tissues that were tested [1].

[1]. Wang, Xueqing; Sarris, Katerina; Kage, Karen; et al. Synthesis and Evaluation of Benzothiazole-Based Analogues as Novel, Potent, and Selective Fatty Acid Amide Hydrolase Inhibitors. Journal of Medicinal Chemistry (2009), 52(1), 170-180. [2]. Meyers, Marvin J.; Long, Scott A.; Pelc, Matthew J.; et al. Discovery of novel spirocyclic inhibitors of fatty acid amide hydrolase (FAAH). Part 1: Identification of 7-azaspiro[3.5]nonane and 1-oxa-8-azaspiro[4.5]decane as lead scaffolds. Bioorganic & Medicinal Chemistry Letters (2011), 21(21), 6538-6544.