Synthesis and evaluation of 3-anilino-quinoxalinones as glycogen phosphorylase inhibitors.
A series of 3-anilino-quinoxalinones has been identified as a new class of glycogen phosphorylase inhibitors. The lead compound 1 was identified through high throughput screening as well as through pharmacophore-based electronic screening. Modifications were made to the scaffold of 1 to produce novel analogues, some of which are 25 times more potent than the lead compound.
Dudash
Joseph
J
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, PO Box 300, Raritan, NJ 08869, USA. jdudash@prdus.jnj.com
Zhang
Yongzheng
Y
Moore
John B
JB
Look
Richard
R
Liang
Yin
Y
Beavers
Mary Pat
MP
Conway
Bruce R
BR
Rybczynski
Philip J
PJ
Demarest
Keith T
KT
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D020128:Inhibitory Concentration 50; D051379:Mice; D008820:Mice, Obese; D011810:Quinoxalines; D013329:Structure-Activity Relationship
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D011810:Quinoxalines; D024981:Glycogen Phosphorylase