7-trifluoromethanesulfonate-3,4-dihydrobenz[h]isoquinolin-1(2H)-one | 928168-23-4

• 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-trifluoromethanesulfonate-3,4-dihydrobenz[h]isoquinolin-1(2H)-one
• CAS: 928168-23-4
• 化学式: C₁₄H₁₀F₃NO₄S
• 分子量: 345.299
• InChiKey: VZYZMWOHBDGCOO-UHFFFAOYSA-N

物化性质

• 熔点：
  144-146 °C(Solvent: Dichloromethane; Hexane)
• 沸点：
  563.8±50.0 °C(predicted)
• 密度：
  1.539±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

反应信息

• 作为反应物：
  描述：

  7-trifluoromethanesulfonate-3,4-dihydrobenz[h]isoquinolin-1(2H)-one 在 四(三苯基膦)钯 六甲基二锡 、 lithium chloride 、 N-溴代丁二酰亚胺(NBS) 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 以80%的产率得到7-bromo-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
• 作为产物：
  描述：

  7-hydroxy-3,4-dihydrobenz[h]isoquinolin-1(2H)-one 、 N-苯基双(三氟甲烷磺酰)亚胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以91%的产率得到7-trifluoromethanesulfonate-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