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

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

  • Bioorg Med Chem Lett. 2013 Dec 15;23(24):6933-7. doi: 10.1016/j.bmcl.2013.09.020.
Kenji Fukunaga 1,  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,  Keiji Yamagami,  Hiroshi Baba,  Takashi Horikawa,  Masatake Fujimura
Affiliations

Affiliation

  • 1 Mitsubishi Tanabe Pharma Corporation, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
PMID: 24176395 DOI: 10.1016/j.bmcl.2013.09.020
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z