Synthesis, SAR studies, and evaluation of 1,4-benzoxazepine derivatives as selective 5-HT1A receptor agonists with neuroprotective effect: Discovery of Piclozotan |
| |
Authors: | Kamei Katsuhide Maeda Noriko Nomura Kayoko Shibata Makoto Katsuragi-Ogino Ryoko Koyama Makoto Nakajima Mika Inoue Teruyoshi Ohno Tomochika Tatsuoka Toshio |
| |
Institution: | Daiichi Asubio Pharma Co., Ltd, 1-1-1, Wakayamadai, Mishima-gun, Osaka 618-8513, Japan. katsuhide_kamei@asubio.co.jp |
| |
Abstract: | A new series of 1,4-benzoxazepine derivatives was designed, synthesized, and evaluated for binding to 5-HT1A receptor and cerebral anti-ischemic effect. A lot of compounds exhibited nanomolar affinity for 5-HT1A receptor with good selectivity over both dopamine D2 and alpha1-adrenergic receptors. Among these compounds, 3-chloro-4-4-4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-yl]butyl]-1, 4-benzoxazepin-5(4H)-one (50: SUN N4057 (Piclozotan) as 2HCl salt) showed remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|