Kamei Katsuhide, Maeda Noriko, Nomura Kayoko, Shibata Makoto, Katsuragi-Ogino Ryoko, Koyama Makoto, Nakajima Mika, Inoue Teruyoshi, Ohno Tomochika, Tatsuoka Toshio
Daiichi Asubio Pharma Co., Ltd, 1-1-1, Wakayamadai, Mishima-gun, Osaka 618-8513, Japan.
Bioorg Med Chem. 2006 Mar 15;14(6):1978-92. doi: 10.1016/j.bmc.2005.10.046. Epub 2005 Nov 14.
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.
设计、合成了一系列新型1,4-苯并二氮杂䓬衍生物，并对其与5-HT1A受体的结合及脑缺血保护作用进行了评估。许多化合物对5-HT1A受体表现出纳摩尔亲和力，对多巴胺D2受体和α1-肾上腺素能受体具有良好的选择性。在这些化合物中，3-氯-4-[4-[4-(2-吡啶基)-1,2,3,6-四氢吡啶-1-基]丁基]-1,4-苯并二氮杂䓬-5(4H)-酮（50：SUN N4057（匹克洛唑坦），以2HCl盐形式）在短暂性大脑中动脉闭塞（t-MCAO）模型中显示出显著的神经保护活性。
