The N-heterocyclic carbene (NHC)-catalyzed enantioselective kinetic resolution of anilides (a kind of hemiaminals) is reported. Upon exposure to the reaction in the presence of an NHC precatalyst and base, catalytic C-O bond formation occurs, providing axially chiral isoindolinones in high yields with excellent enantioselectivities.
The unprecedented enantioselective aza-benzoin reaction of aldehydes with 2H-azirines was developed by utilizing a chiral N-heterocyclic carbene as the catalyst. A wide range of corresponding aziridines can be obtained in good yields with high enantioselectivities. The obtained optically active aziridines should be useful in the synthesis of other valuable molecules.
Liver fructose-1,6-bisphosphatase
(FBPase) is a key enzyme in the
gluconeogenesis pathway. Inhibiting FBPase activity represents a potential
treatment for type 2 diabetes mellitus. A series of novel N-arylsulfonyl-4-arylamino-indole-2-carboxamide derivatives
have been disclosed as FBPase inhibitors. Through extensive structure–activity
relationship investigations, a promising candidate molecule Cpd118 [sodium (7-chloro-4-((3-methoxyphenyl)amino)-1-methyl-1H-indole-2-carbonyl] [(4-methoxyphenyl)sulfonyl)amide] has
been identified with high inhibitory activity against human liver
FBPase (IC50, 0.029 ± 0.006 μM) and high selectivity
relative to the other six AMP-binding enzymes. Importantly, Cpd118 produced significant glucose-lowering effects on both
type 2 diabetic KKAy mice and ZDF rats as demonstrated by substantial
reductions in the fasting and postprandial blood glucose levels, as
well as the HbA1c level. Furthermore, Cpd118 elicited
a favorable pharmacokinetic profile with an oral bioavailability of
99.1%. Moreover, the X-ray crystal structure of the Cpd118–FBPase complex was resolved, which revealed a unique binding
mode and provided a structural basis for its high potency and selectivity.
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