1246032-55-2Relevant academic research and scientific papers
Nickel-Catalyzed Cross-Coupling of Redox-Active Esters with Boronic Acids
Wang, Jie,Qin, Tian,Chen, Tie-Gen,Wimmer, Laurin,Edwards, Jacob T.,Cornella, Josep,Vokits, Benjamin,Shaw, Scott A.,Baran, Phil S.
supporting information, p. 9676 - 9679 (2016/08/10)
A transformation analogous in simplicity and functional group tolerance to the venerable Suzuki cross-coupling between alkyl-carboxylic acids and boronic acids is described. This Ni-catalyzed reaction relies upon the activation of alkyl carboxylic acids as their redox-active ester derivatives, specifically N-hydroxy-tetrachlorophthalimide (TCNHPI), and proceeds in a practical and scalable fashion. The inexpensive nature of the reaction components (NiCl2?6 H2O—$9.5 mol?1, Et3N) coupled to the virtually unlimited commercial catalog of available starting materials bodes well for its rapid adoption.
Discovery and optimization of piperidyl-1,2,3-triazole ureas as potent, selective, and in vivo-active inhibitors of α/β-hydrolase domain containing 6 (ABHD6)
Hsu, Ku-Lung,Tsuboi, Katsunori,Chang, Jae Won,Whitby, Landon R.,Speers, Anna E.,Pugh, Holly,Cravatt, Benjamin F.
supporting information, p. 8270 - 8279 (2013/12/04)
α/β-Hydrolase domain containing 6 (ABHD6) is a transmembrane serine hydrolase that hydrolyzes the endogenous cannabinoid 2- arachidonoylglycerol (2-AG) to regulate certain forms of cannabinoid receptor-dependent signaling in the nervous system. The full spectrum of ABHD6 metabolic activities and functions is currently unknown and would benefit from selective, in vivo-active inhibitors. Here, we report the development and characterization of an advanced series of irreversible (2-substituted)- piperidyl-1,2,3-triazole urea inhibitors of ABHD6, including compounds KT182 and KT203, which show exceptional potency and selectivity in cells (-1), act as systemic and peripherally restricted ABHD6 inhibitors, respectively. We also describe an orally bioavailable ABHD6 inhibitor, KT185, that displays excellent selectivity against other brain and liver serine hydrolases in vivo. We thus describe several chemical probes for biological studies of ABHD6, including brain-penetrant and peripherally restricted inhibitors that should prove of value for interrogating ABHD6 function in animal models.
