1-(3-Deoxy-3-fluoro-β-d-glucopyranosyl) pyrimidine derivatives as inhibitors of glycogen phosphorylase b: Kinetic, crystallographic and modelling studies

Vicky G. Tsirkone, Evangelia Tsoukala, Christos Lamprakis, Stella Manta, Joseph M. Hayes, Vicky T. Skamnaki, Christina Drakou, Spyros E. Zographos, Dimitri Komiotis, Demetres D. Leonidas, Vicky G. Tsirkone, Evangelia Tsoukala, Christos Lamprakis, Stella Manta, Joseph M. Hayes, Vicky T. Skamnaki, Christina Drakou, Spyros E. Zographos, Dimitri Komiotis, Demetres D. Leonidas

Index: Bioorg. Med. Chem. 18 , 3413-25, (2010)

Full Text: HTML

Abstract

The catalytic site of muscle glycogen phosphorylase b (GPb) has been probed with five fluorine glucose derivatives. These inhibitors had fluorine instead of hydroxyl at the 3′ position of the glucose moiety and a variety of pyrimidine derivatives at the 1′ position. The best of this carbohydrate-based family of five inhibitors displays a K i value of 46 μM.