5-Chloroindoloyl glycine amide inhibitors of glycogen phosphorylase: synthesis, in vitro, in vivo, and X-ray crystallographic characterization

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Abstract

The synthesis, in vitro, and in vivo biological characterization of a series of achiral 5-chloroindoloyl glycine amide inhibitors of human liver glycogen phosphorylase A are described. Improved potency over previously reported compounds in cellular and in vivo assays was observed. The allosteric binding site of these compounds was shown by X-ray crystallography to be the same as that reported previously for 5-chloroindoloyl norstatine amides.

Graphical abstract

Glycine amide inhibitors of human liver glycogen phosphorylase A with improved potency in vivo are reported.

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Acknowledgements

The authors wish to thank Philip H. Sarges and Katie L. Dugas for assistance with some of the biological assays and Dennis J. Hoover, Ronald B. Gammill, and Bernard Hulin for helpful discussions during the course of this work. The authors also wish to thank Gregory D. Berger and Ralph W. Stevenson for their support of this work.

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