7-(7-chloro-1H-indol-1-yl)-9-methoxy-4-(pyridin-3-ylmethyl)-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-(7-chloro-1H-indol-1-yl)-9-methoxy-4-(pyridin-3-ylmethyl)-2,3,4,5-tetrahydrobenzo[f ][1,4]oxazepine
• 英文别名: 7-(7-chloroindol-1-yl)-9-methoxy-4-(pyridin-3-ylmethyl)-3,5-dihydro-2H-1,4-benzoxazepine
• 化学式: C₂₄H₂₂ClN₃O₂
• 分子量: 419.911
• InChiKey: SYTCTLNEASOHAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  39.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  7-bromo-9-methoxy-2,3-dihydrobenzo[f][1,4]oxazepine 在 sodium tetrahydroborate 、 potassium phosphate 、 copper(l) iodide 、 三乙酰氧基硼氢化钠 、 (1S,2S)-(+)-N,N'-二甲基环己烷-1,2-二胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 18.83h， 生成 7-(7-chloro-1H-indol-1-yl)-9-methoxy-4-(pyridin-3-ylmethyl)-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