Scaffold hopping and optimization towards libraries of glycogen synthase kinase-3 inhibitors.
Using a virtual screening strategy based on a methodology derived from the CATS molecular descriptor, a novel compound class with inhibitory activity against the GSK-3 enzyme was identified through scaffold hopping. These compounds were readily synthesized, either by solid-phase or solution-phase chemistry. Compounds with inhibitory activity below 1 microM were identified.
Naerum
Lars
L
Medicinal Chemistry Research, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark.
Nørskov-Lauritsen
Leif
L
Olesen
Preben H
PH
D020650:Combinatorial Chemistry Techniques / Q000379:methods* / Q000706:statistics & numerical data; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D038362:Glycogen Synthase Kinase 3