A new class of glycogen phosphorylase inhibitors.
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.
Department of Basic Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. zhijian_lu@merck.com
Zhijian
Z
Lu
Joann
J
Bohn
Raynald
R
Bergeron
Qiaolin
Q
Deng
Kenneth P
KP
Ellsworth
Wayne M
WM
Geissler
Georgianna
G
Harris
Peggy E
PE
McCann
Brian
B
McKeever
Robert W
RW
Myers
Richard
R
Saperstein
Christopher A
CA
Willoughby
Jun
J
Yao
Kevin
K
Chapman
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009284:Naphthols / Q000138:chemical synthesis* / Q000494:pharmacology; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D009284:Naphthols; D000255:Adenosine Triphosphate; D024981:Glycogen Phosphorylase