7-hydroxy-3,4-dihydrobenz[h]isoquinolin-1(2H)-one | 928168-22-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 7-hydroxy-3,4-dihydrobenz[h]isoquinolin-1(2H)-one
• 英文别名: 7-hydroxy-3,4-dihydro-2H-benzo[h]isoquinolin-1-one
• CAS: 928168-22-3
• 化学式: C₁₃H₁₁NO₂
• 分子量: 213.236
• InChiKey: OIEFHFOTAFGDAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-hydroxy-3,4-dihydrobenz[h]isoquinolin-1(2H)-one 在 硼烷 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 1,2,3,4-Tetrahydrobenzo[h]isoquinolin-7-ol
  参考文献：
  名称：

  Exploring the active site of phenylethanolamine N-methyltransferase with 1,2,3,4-tetrahydrobenz[h]isoquinoline inhibitors☆

  摘要：

  1,2,3,4-Tetrahydrobenz[h]isoquinoline (THBQ, 11) is a potent, inhibitor of phenylethanolamine N-methyltransferase (PNMT). Docking studies indicated that the enhanced PNMT inhibitory potency of 11 (hPNMT K-i = 0.49 mu M) versus 1,2,3,4-tetrahydroisoquinoline (5, hPNMT Ki = 5.8 mu M) was likely due to hydrophobic interactions with Val53, Met258, Val272, and Val269 in the PNMT active site. These studies also suggested that the addition of substituents to the 7-position of 11 that are capable of forming hydrogen bonds to the enzyme could lead to compounds (14-18) having enhanced PNMT inhibitory potency. However, these compounds are in fact less potent at PNMT than 11. Furthermore, 7-bromo-THBQ (19, hPNMT Ki = 0.22 mM), which has a lipophilic 7-substituent that cannot hydrogen bond to the enzyme, is twice as potent at PNMT than 11. This once again illustrates the limitations of docking studies for lead optimization. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.010
• 作为产物：
  描述：

  7-methoxy-3,4-dihydrobenz[h]isoquinolin-1(2H)-one 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 2.0h， 以90%的产率得到7-hydroxy-3,4-dihydrobenz[h]isoquinolin-1(2H)-one
  参考文献：
  名称：

  Exploring the active site of phenylethanolamine N-methyltransferase with 1,2,3,4-tetrahydrobenz[h]isoquinoline inhibitors☆

  摘要：

  1,2,3,4-Tetrahydrobenz[h]isoquinoline (THBQ, 11) is a potent, inhibitor of phenylethanolamine N-methyltransferase (PNMT). Docking studies indicated that the enhanced PNMT inhibitory potency of 11 (hPNMT K-i = 0.49 mu M) versus 1,2,3,4-tetrahydroisoquinoline (5, hPNMT Ki = 5.8 mu M) was likely due to hydrophobic interactions with Val53, Met258, Val272, and Val269 in the PNMT active site. These studies also suggested that the addition of substituents to the 7-position of 11 that are capable of forming hydrogen bonds to the enzyme could lead to compounds (14-18) having enhanced PNMT inhibitory potency. However, these compounds are in fact less potent at PNMT than 11. Furthermore, 7-bromo-THBQ (19, hPNMT Ki = 0.22 mM), which has a lipophilic 7-substituent that cannot hydrogen bond to the enzyme, is twice as potent at PNMT than 11. This once again illustrates the limitations of docking studies for lead optimization. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.010