Add time:07/13/2019         Source:sciencedirect.com

As a result of the various N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives with a hydroxy moiety synthesized in an effort to discover novel glycogen phosphorylase (GP) inhibitors, 5-chloro-N-(5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide (5b) was found to have potent inhibitory activity. The introduction of fluorine atoms both at a position adjacent to the hydroxy group and in the central benzene moiety lead to the optically active derivative 5-chloro-N-[(5R)-1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1H-indole-2-carboxamide (25eα, which was the most potent compound in this series (IC50 = 0.020 μM). This compound inhibited glucagon-induced glucose output in cultured primary hepatocytes with an IC50 value of 0.69 μM, and showed oral hypoglycemic activity in diabetic db/db mice at 10 mg/kg. Compound 25eα also had an excellent pharmacokinetic profile, with high oral bioavailability and a long plasma half-life, in male SD rats. The binding mode of 25eα to this molecule and the role of fluorine atoms in that binding were speculated in an enzyme docking study.

We also recommend Trading Suppliers and Manufacturers of 1H-INDOLE-5-CARBOXAMIDE, 97% (cas 1670-87-7). Pls Click Website Link as below: cas 1670-87-7 suppliers