5-Chloroindoloyl glycine amide inhibitors of glycogen phosphorylase: synthesis, in vitro, in vivo, and X-ray crystallographic characterization
Graphical abstract
Glycine amide inhibitors of human liver glycogen phosphorylase A with improved potency in vivo are reported.
Section snippets
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.
References and notes (19)
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2022, Bioorganic ChemistryCitation Excerpt :A glycogen-synthetic assay system is commonly used to assay phosphorylase activity by detecting the release of inorganic phosphate in the direction of glycogen synthesis [21]. In this study, the activity of RMGPa was measured, and the reported compound PSN-357, which has entered phase II clinical trials as a GP inhibitor [22], was used as the positive control. In the structure–activity relationship (SAR) exploration, we first investigated the effects of different indole substituents on the activity by transforming the substituent groups on the indole aromatic ring.
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