np-031112 and Mood-Disorders

np-031112 has been researched along with Mood-Disorders* in 1 studies

Other Studies

1 other study(ies) available for np-031112 and Mood-Disorders

ArticleYear
Hit Optimization of 5-Substituted-N-(piperidin-4-ylmethyl)-1H-indazole-3-carboxamides: Potent Glycogen Synthase Kinase-3 (GSK-3) Inhibitors with in Vivo Activity in Model of Mood Disorders.
    Journal of medicinal chemistry, 2015, Nov-25, Volume: 58, Issue:22

    Novel treatments for bipolar disorder with improved efficacy and broader spectrum of activity are urgently needed. Glycogen synthase kinase 3β (GSK-3β) has been suggested to be a key player in the pathophysiology of bipolar disorder. A series of novel GSK-3β inhibitors having the common N-[(1-alkylpiperidin-4-yl)methyl]-1H-indazole-3-carboxamide scaffold were prepared taking advantage of an X-ray cocrystal structure of compound 5 with GSK-3β. We probed different substitutions at the indazole 5-position and at the piperidine-nitrogen to obtain potent ATP-competitive GSK-3β inhibitors with good cell activity. Among the compounds assessed in the in vivo PK experiments, 14i showed, after i.p. dosing, encouraging plasma PK profile and brain exposure, as well as efficacy in a mouse model of mania. Compound 14i was selected for further in vitro/in vivo pharmacological evaluation, in order to elucidate the use of ATP-competitive GSK-3β inhibitors as new tools in the development of new treatments for mood disorders.

    Topics: Adenosine Triphosphate; Amphetamine; Animals; Binding, Competitive; Central Nervous System Stimulants; CHO Cells; Cricetinae; Cricetulus; Enzyme Inhibitors; Glycogen Synthase Kinase 3; High-Throughput Screening Assays; Humans; Injections, Intraperitoneal; Male; Mice; Mice, Inbred C57BL; Models, Molecular; Mood Disorders; Motor Activity; Phosphorylation; Structure-Activity Relationship; tau Proteins; X-Ray Diffraction

2015