A new class of glycogen phosphorylase inhibitors

Zhijian Lu; Joann Bohn; Raynald Bergeron; Qiaolin Deng; Kenneth P Ellsworth; Wayne M Geissler; Georgianna Harris; Peggy E McCann; Brian McKeever; Robert W Myers; Richard Saperstein; Christopher A Willoughby; Jun Yao; Kevin Chapman

doi:10.1016/j.bmcl.2003.08.046

A new class of glycogen phosphorylase inhibitors

Bioorg Med Chem Lett. 2003 Nov 17;13(22):4125-8. doi: 10.1016/j.bmcl.2003.08.046.

Authors

Zhijian Lu¹, Joann Bohn, Raynald Bergeron, Qiaolin Deng, Kenneth P Ellsworth, Wayne M Geissler, Georgianna Harris, Peggy E McCann, Brian McKeever, Robert W Myers, Richard Saperstein, Christopher A Willoughby, Jun Yao, Kevin Chapman

Affiliation

¹ Department of Basic Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. [email protected]

PMID: 14592521
DOI: 10.1016/j.bmcl.2003.08.046

Abstract

A new class of diacid analogues that binds at the AMP site not only are very potent but have approximately 10-fold selectivity in liver versus muscle glycogen phosphorylase (GP) in the in vitro assay. The synthesis, structure, and in vitro and in vivo biological evaluation of these liver selective glycogen phosphorylase inhibitors are discussed.

MeSH terms

Adenosine Triphosphate / metabolism
Amino Acid Sequence
Animals
Binding Sites
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Glycogen Phosphorylase / antagonists & inhibitors*
Glycogen Phosphorylase / chemistry
Kinetics
Liver / enzymology
Mice
Models, Molecular
Molecular Conformation
Naphthols / chemical synthesis*
Naphthols / pharmacology
Protein Conformation
Rats
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Naphthols
Adenosine Triphosphate
Glycogen Phosphorylase