N-4-((E)-3-{5-[bis(tert-butoxycarbonyl)]amino-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indol-3-yl}-3-oxo-1-propenyl)benzyl-N,N-dimethyl-N-[(1-methyl-5-methylsulfonyl-2-pyrrolyl)methyl]ammonium bromide | 1017278-88-4

• 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: N-4-((E)-3-{5-[bis(tert-butoxycarbonyl)]amino-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indol-3-yl}-3-oxo-1-propenyl)benzyl-N,N-dimethyl-N-[(1-methyl-5-methylsulfonyl-2-pyrrolyl)methyl]ammonium bromide
• CAS: 1017278-88-4
• 化学式: Br*C₄₂H₅₂ClN₄O₇S
• 分子量: 872.32
• InChiKey: AAIRLWRYNSIDAJ-UXJRWBAGSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  5.42
• 重原子数：
  56.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  115.22
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  N-4-((E)-3-{5-[bis(tert-butoxycarbonyl)]amino-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indol-3-yl}-3-oxo-1-propenyl)benzyl-N,N-dimethyl-N-[(1-methyl-5-methylsulfonyl-2-pyrrolyl)methyl]ammonium bromide 在 氢溴酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 15.0h， 以80%的产率得到(E)-N-(4-(3-(5-amino-1-(chloromethyl)-1H-benzo[e]indol-3(2H)-yl)-3-oxoprop-1-enyl)benzyl)-N,N-dimethyl-1-(1-methyl-5-(methylsulfonyl)-1H-pyrrol-2-yl)methanaminium bromide hydrobromide
  参考文献：
  名称：

  Weight loss effects of quaternary salts of 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indoles; structure–activity relationships

  摘要：

  Quaternary salt analogues based on the DNA minor groove binder and adenine N3 alkylating agent 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indole (aminoCBI) show remarkable effects on the body weight of mice (a long-term failure to gain weight relative to matched controls with no loss of appetite or perceptible deterioration in health) following administration of a single (non-toxic) dose between about 0.5-5 mu mol/kg. The nature of the quaternizing group was not important, but a related hydroxyCBI analogue was much less effective. Compounds where the chloro group was replaced by a hydrogen or hydroxy group (thus abrogating DNA alkylating capability) showed no weight control activity. It is speculated, based on other studies, that the marked long-term weight control effect is due to inhibition of bile flow into the intestine and reduced absorption of triglycerides, together with accelerated cell death in spleen and white adipose tissues due to drug accumulation there. This class of compound may serve as interesting tools for further study of these phenomena. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.007
• 作为产物：
  描述：

  tert-butyl N-[1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-yl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 84.75h， 生成 N-4-((E)-3-{5-[bis(tert-butoxycarbonyl)]amino-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indol-3-yl}-3-oxo-1-propenyl)benzyl-N,N-dimethyl-N-[(1-methyl-5-methylsulfonyl-2-pyrrolyl)methyl]ammonium bromide
  参考文献：
  名称：

  Weight loss effects of quaternary salts of 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indoles; structure–activity relationships

  摘要：

  Quaternary salt analogues based on the DNA minor groove binder and adenine N3 alkylating agent 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indole (aminoCBI) show remarkable effects on the body weight of mice (a long-term failure to gain weight relative to matched controls with no loss of appetite or perceptible deterioration in health) following administration of a single (non-toxic) dose between about 0.5-5 mu mol/kg. The nature of the quaternizing group was not important, but a related hydroxyCBI analogue was much less effective. Compounds where the chloro group was replaced by a hydrogen or hydroxy group (thus abrogating DNA alkylating capability) showed no weight control activity. It is speculated, based on other studies, that the marked long-term weight control effect is due to inhibition of bile flow into the intestine and reduced absorption of triglycerides, together with accelerated cell death in spleen and white adipose tissues due to drug accumulation there. This class of compound may serve as interesting tools for further study of these phenomena. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.007