Convenient synthetic method for 3-(3-substituted indol-2-yl)quinoxalin-2- ones as VEGF inhibitor

フォーマット:

論文

責任表示:

Aoki, Katsuyuki ; Koseki, Jun-ichi ; Takeda, Shuichi ; Aburada, Masaki ; Miyamoto, Kenichi

言語:

英語

出版情報:

日本薬学会, 2007-06-01

著者名:

• Aoki, Katsuyuki
• Koseki, Jun-ichi
• Takeda, Shuichi
• Aburada, Masaki
• Miyamoto, Kenichi

掲載情報:

Chemical and Pharmaceutical Bulletin

ISSN:

0009-2363      

巻:

55

通号:

6

開始ページ:

922

終了ページ:

925

バージョン:

publisher

概要:

金沢大学医学部附属病院薬剤部<br />It has already been reported that 3-(indol-2-yl)quinoxalin-2-ones 1)? have a potent inhibitory effect on the growth of tumor cells based on anti-angiogenesis activity. We have also carried out a structure-activity … relationship (SAR) study of 3-(indol-2-yl)quinoxalin-2-ones, which showed a potent inhibitory activity toward the vascular endothelial growth factor (VEGF)-induced proliferation of human mesangial cells and the VEGF-induced auto-phosphorylation of human umbilical vein endothelial cells.2) Moreover, one of these compounds has a potent medicinal effect based on anti-angiogenic action, by oral administration2) (Chart 1, 9). However, since the existing synthetic methods1) for the preparation of 3-(indol-2-yl)quinoxalin-2-ones consist of multiple steps some of which require strict anhydrous conditions, a convenient and simple synthetic method in place of the existing method is desirable. As a result of the investigations into the synthetic procedures, 3-(3-substituted indol-2-yl)quinoxalin-2-ones can be easily prepared by the condensation of 3-substituted indoles with quinoxalin-2-ones in the presence of trifluoroacetic acid (TFA). Herein, we report the examination of these reaction conditions and the application of this new synthetic method to the synthesis of the derivatives as VEGF inhibitors. © 2007 Pharmaceutical Society of Japan. 続きを見る

URL:

http://hdl.handle.net/2297/6594