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

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• 作者：Kenji Fukunaga ; Fumiaki Uehara ; Keiichi Aritomo ; Aya Shoda ; Shinsuke Hiki ; Masahiro Okuyama ; Yoshihiro Usui ; Kazutoshi Watanabe ; Koichi Yamakoshi ; Toshiyuki Kohara ; Tokushi Hanano ; Hiroshi Tanaka ; Susumu Tsuchiya ; Shinji Sunada ; Ken-Ichi Saito ; Jun-ichi Eguchi ; Satoshi Yuki ; Shoichi Asano ; Shinji Tanaka ; Akiko Mori ; et al.
• 关键词：Glycogen synthase kinase-3尾 ; Alzheimer&rsquo ; s disease ; Tau protein ; Hyperphosphorylation
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：15 December, 2013
• 年：2013
• 卷：23
• 期：24
• 页码：6933-6937
• 全文大小：1049 K

文摘

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