Kozikowski, Alan P.’s team published research in ChemMedChem in 6 | CAS: 170364-89-3

ChemMedChem published new progress about 170364-89-3. 170364-89-3 belongs to piperidines, auxiliary class Indole,Piperidine,Amide, name is tert-Butyl 4-(1H-indol-1-yl)piperidine-1-carboxylate, and the molecular formula is C18H24N2O2, HPLC of Formula: 170364-89-3.

Kozikowski, Alan P. published the artcileIdentification of a Glycogen Synthase Kinase-3β Inhibitor that Attenuates Hyperactivity in CLOCK Mutant Mice, HPLC of Formula: 170364-89-3, the publication is ChemMedChem (2011), 6(9), 1593-1602, database is CAplus and MEDLINE.

Bipolar disorder is characterized by a cycle of mania and depression, which affects approx. 5 million people in the United States. Current treatment regimes include the so-called “mood-stabilizing drugs”, such as lithium and valproate that are relatively dated drugs with various known side effects. Glycogen synthase kinase-3β (GSK-3β) plays a central role in regulating circadian rhythms, and lithium is known to be a direct inhibitor of GSK-3β. We designed a series of second generation benzofuran-3-yl-(indol-3-yl)maleimides containing a piperidine ring that possess IC50 values in the range of 4 to 680 nM against human GSK-3β. Compound 3a (I) exhibits reasonable kinase selectivity and promising preliminary absorption, distribution, metabolism, and excretion (ADME) data. The administration of this compound at doses of 10 to 25 mg kg-1 resulted in the attenuation of hyperactivity in amphetamine/chlordiazepoxide-induced manic-like mice together with enhancement of prepulse inhibition, similar to the effects found for valproate (400 mg kg-1) and the antipsychotic haloperidol (1 mg kg-1). We also tested this compound in mice carrying a mutation in the central transcriptional activator of mol. rhythms, the CLOCK gene, and found that the same compound attenuates locomotor hyperactivity in response to novelty. This study further demonstrates the use of inhibitors of GSK-3β in the treatment of manic episodes of bipolar/mood disorders, thus further validating GSK-3β as a relevant therapeutic target in the identification of new therapies for bipolar patients.

ChemMedChem published new progress about 170364-89-3. 170364-89-3 belongs to piperidines, auxiliary class Indole,Piperidine,Amide, name is tert-Butyl 4-(1H-indol-1-yl)piperidine-1-carboxylate, and the molecular formula is C18H24N2O2, HPLC of Formula: 170364-89-3.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem