1165799-99-4Relevant academic research and scientific papers
Design of small molecule inhibitors of acetyl-CoA carboxylase 1 and 2 showing reduction of hepatic malonyl-CoA levels in vivo in obese Zucker rats
Bengtsson, Christoffer,Blaho, Stefan,Saitton, David Blomberg,Brickmann, Kay,Broddefalk, Johan,Davidsson, ?jvind,Drmota, Tomas,Folmer, Rutger,Hallberg, Kenth,Hallén, Stefan,Hovland, Ragnar,Isin, Emre,Johannesson, Petra,Kull, Bengt,Larsson, Lars-Olof,L?fgren, Lars,Nilsson, Kristina E.,Noeske, Tobias,Oakes, Nick,Plowright, Alleyn T.,Schnecke, Volker,Sthlberg, Pernilla,S?rme, Pernilla,Wan, Hong,Wellner, Eric,?ster, Linda
supporting information; experimental part, p. 3039 - 3053 (2011/06/27)
Inhibition of acetyl-CoA carboxylases has the potential for modulating long chain fatty acid biosynthesis and mitochondrial fatty acid oxidation. Hybridization of weak inhibitors of ACC2 provided a novel, moderately potent but lipophilic series. Optimization led to compounds 33 and 37, which exhibit potent inhibition of human ACC2, 10-fold selectivity over inhibition of human ACC1, good physical and in vitro ADME properties and good bioavailability. X-ray crystallography has shown this series binding in the CT-domain of ACC2 and revealed two key hydrogen bonding interactions. Both 33 and 37 lower levels of hepatic malonyl-CoA in vivo in obese Zucker rats.
NEW ACETYL COENZYME A CARBOXYLASE (ACC) INHIBITORS AND USES IN TREATMENTS OF OBESITY AND DIABETES MELLITUS - 087
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Page/Page column 234, (2009/07/25)
The present invention relates to Acetyl Coenzyme A Carboxylase (ACC) inhibitors according to formula (I), or an enantiomer thereof, or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, E, L, Z and n are as defined herein, to processes for preparing such compounds, to pharmaceutical compositions containing them, to the use of such inhibitors and to methods for th eir therapeutic use, particularly in the treatments of obesity and diabetes mellitus.
