7-(benzo[b]thiophen-3-yl)-9-methoxy-4-(4-methoxybenzyl)-2,3,4,5-tetrahydrobenzo[f ][1,4]oxazepine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 7-(benzo[b]thiophen-3-yl)-9-methoxy-4-(4-methoxybenzyl)-2,3,4,5-tetrahydrobenzo[f ][1,4]oxazepine
• 英文别名: 7-(1-benzothiophen-3-yl)-9-methoxy-4-[(4-methoxyphenyl)methyl]-3,5-dihydro-2H-1,4-benzoxazepine
• 化学式: C₂₆H₂₅NO₃S
• 分子量: 431.555
• InChiKey: APJHQPWHZVSVJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  59.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-溴-2-羟基-3-甲氧基苯甲醛 在 sodium tetrahydroborate 、 potassium phosphate 、 palladium diacetate 、 三乙酰氧基硼氢化钠 、 对甲苯磺酸 、 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 甲苯 、 正丁醇 为溶剂， 反应 30.5h， 生成 7-(benzo[b]thiophen-3-yl)-9-methoxy-4-(4-methoxybenzyl)-2,3,4,5-tetrahydrobenzo[f ][1,4]oxazepine
  参考文献：
  名称：

  A Selective Prostaglandin E₂ Receptor Subtype 2 (EP2) Antagonist Increases the Macrophage-Mediated Clearance of Amyloid-Beta Plaques

  摘要：

  A high-throughput screen resulted in the discovery of benzoxazepine 1, an EP2 antagonist possessing low microsomal stability and potent CYP3A4 inhibition. Modular optimization of lead compound 1 resulted in the discovery of benzoxazepine 52, a molecule with single-digit nM binding affinity for the EP2 receptor and significantly improved microsomal stability. It was devoid of CYP inhibition and was similar to 4000-fold selective against the other EP receptors. Compound 52 was shown to have good PK properties in CD-1 mice and high CNS permeability in C57Bl/6s mice and Sprague-Dawley rats. In an ex vivo assay, it demonstrated the ability to increase the macrophage-mediated clearance of amyloid-beta plaques from brain slices in a dose-dependent manner.

  DOI：

  10.1021/acs.jmedchem.5b00567

文献信息

• A Selective Prostaglandin E₂ Receptor Subtype 2 (EP2) Antagonist Increases the Macrophage-Mediated Clearance of Amyloid-Beta Plaques
  作者：Brian M. Fox、Hilary P. Beck、Philip M. Roveto、Frank Kayser、Qingwen Cheng、Hannah Dou、Toni Williamson、James Treanor、Hantao Liu、Lixia Jin、Guifen Xu、Ji Ma、Songli Wang、Steven H. Olson

  DOI：10.1021/acs.jmedchem.5b00567

  日期：2015.7.9

  A high-throughput screen resulted in the discovery of benzoxazepine 1, an EP2 antagonist possessing low microsomal stability and potent CYP3A4 inhibition. Modular optimization of lead compound 1 resulted in the discovery of benzoxazepine 52, a molecule with single-digit nM binding affinity for the EP2 receptor and significantly improved microsomal stability. It was devoid of CYP inhibition and was similar to 4000-fold selective against the other EP receptors. Compound 52 was shown to have good PK properties in CD-1 mice and high CNS permeability in C57Bl/6s mice and Sprague-Dawley rats. In an ex vivo assay, it demonstrated the ability to increase the macrophage-mediated clearance of amyloid-beta plaques from brain slices in a dose-dependent manner.