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Bioorg Med Chem Lett. 2013 Dec 15;23(24):6933-7. doi: 10.1016/j.bmcl.2013.09.020. Epub 2013 Sep 21.

2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; a new class of potent, selective and orally active glycogen synthase kinase-3β inhibitors.

Author information

1
Mitsubishi Tanabe Pharma Corporation, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.

Abstract

A series of 2-(2-phenylmorpholin-4-yl)pyrimidin-4(3H)-ones was synthesized and examined for their inhibitory activity against glycogen synthase kinase-3β (GSK-3β). We found 21, 29 and 30 to possess potent in vitro GSK-3β inhibitory activity with good in vitro PK profiles. 21 demonstrated significant decrease of tau phosphorylation after oral administration in mice and excellent PK profiles.

KEYWORDS:

Alzheimer’s disease; Glycogen synthase kinase-3β; Hyperphosphorylation; Tau protein

PMID:
24176395
DOI:
10.1016/j.bmcl.2013.09.020
[Indexed for MEDLINE]

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