(6RS,11aSR)-2-isopropyloxycarbonyl-6-trans-cinnamoylmethyl-7,8,10-trimethoxy-9-methyl-1,2,3,6,11,11a-hexahydro-pyrazino[1,2-b]isoquinolin-4-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (6RS,11aSR)-2-isopropyloxycarbonyl-6-trans-cinnamoylmethyl-7,8,10-trimethoxy-9-methyl-1,2,3,6,11,11a-hexahydro-pyrazino[1,2-b]isoquinolin-4-one
• 英文别名: propan-2-yl (6R,11aS)-7,8,10-trimethoxy-9-methyl-4-oxo-6-[[(E)-3-phenylprop-2-enoyl]oxymethyl]-3,6,11,11a-tetrahydro-1H-pyrazino[1,2-b]isoquinoline-2-carboxylate
• 化学式: C₃₀H₃₆N₂O₈
• 分子量: 552.624
• InChiKey: BSFYBCCPIHLXCV-OIYLYIPGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (6RS,11aSR)-6-hydroxymethyl-2-isopropyloxycarbonyl-7,8,10-trimethoxy-9-methyl-1,2,3,6,11,11a-hexahydro-pyrazino[1,2-b]isoquinolin-4-one 、 肉桂酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 21.0h， 以90%的产率得到(6RS,11aSR)-2-isopropyloxycarbonyl-6-trans-cinnamoylmethyl-7,8,10-trimethoxy-9-methyl-1,2,3,6,11,11a-hexahydro-pyrazino[1,2-b]isoquinolin-4-one
  参考文献：
  名称：

  Pyrazino[1,2-b]isoquinolines: Synthesis and study of their cytostatic and cytotoxic properties

  摘要：

  The in vitro antitumor potential of novel pyrazino[1,2-b]-isoquinoline-4-ones that contain a half portion of significant natural products was explored in three cancer cell lines: MDA-MB 231 human breast carcinoma, A-549 human lung carcinoma, and HT-29 human colon carcinoma. In general, these compounds show mid to low mu M GI(50)s, but LC(50)s over 100 mu M with the exceptions of compounds 3b and 31 that are moderately toxic in all cell lines, while compound 4a is highly toxic and selective for HT-29 cells with LC50 values in the high nanomolar range. Experiments directed to elucidate possible mechanisms of action with compounds 3a, 29, and 31 showed that compound 3a is able to efficiently induce apoptosis triggered directly from the G2/M phase of cell cycle, while compounds 29 and 31 are potentially cytostatic agents that induce the G1/S arrest of cell cycle. All three compounds do not act through DNA damage, since they do not activate this signaling at the level of sensors, transducers, and executers. Furthermore, the apoptosis induction of 3a is not mediated by activation of pro-apoptotic kinases JNK and p38 or by activation of AKT. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.083

文献信息

• Pyrazino[1,2-b]isoquinolines: Synthesis and study of their cytostatic and cytotoxic properties
  作者：Irene Ortín、Juan Francisco González、Elena de la Cuesta、Cristina Manguan-García、Rosario Perona、Carmen Avendaño

  DOI：10.1016/j.bmc.2008.07.083

  日期：2008.10

  The in vitro antitumor potential of novel pyrazino[1,2-b]-isoquinoline-4-ones that contain a half portion of significant natural products was explored in three cancer cell lines: MDA-MB 231 human breast carcinoma, A-549 human lung carcinoma, and HT-29 human colon carcinoma. In general, these compounds show mid to low mu M GI(50)s, but LC(50)s over 100 mu M with the exceptions of compounds 3b and 31 that are moderately toxic in all cell lines, while compound 4a is highly toxic and selective for HT-29 cells with LC50 values in the high nanomolar range. Experiments directed to elucidate possible mechanisms of action with compounds 3a, 29, and 31 showed that compound 3a is able to efficiently induce apoptosis triggered directly from the G2/M phase of cell cycle, while compounds 29 and 31 are potentially cytostatic agents that induce the G1/S arrest of cell cycle. All three compounds do not act through DNA damage, since they do not activate this signaling at the level of sensors, transducers, and executers. Furthermore, the apoptosis induction of 3a is not mediated by activation of pro-apoptotic kinases JNK and p38 or by activation of AKT. (C) 2008 Elsevier Ltd. All rights reserved.