1-((benzyloxy)(3-(trimethylammonio)propyl)amino)-1-oxododecan-2-aminium dichloride | 1260652-87-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-((benzyloxy)(3-(trimethylammonio)propyl)amino)-1-oxododecan-2-aminium dichloride
• 英文别名: 3-[2-Azaniumyldodecanoyl(phenylmethoxy)amino]propyl-trimethylazanium;dichloride；3-[2-azaniumyldodecanoyl(phenylmethoxy)amino]propyl-trimethylazanium;dichloride
• CAS: 1260652-87-6
• 化学式: C₂₅H₄₆N₃O₂*ClH*Cl
• 分子量: 492.573
• InChiKey: QTTXVEPVTMYPIB-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  2.33
• 重原子数：
  32
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-((benzyloxy)(3-(trimethylammonio)propyl)amino)-1-oxododecan-2-aminium dichloride 在 20 % Pd(OH)2/C on charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、303.99 kPa 条件下， 反应 18.0h， 以52%的产率得到1-(hydroxy[3-(trimethylammonio)propyl]amino)-1-oxododecan-2-aminium dichloride
  参考文献：
  名称：

  2-Aminohydroxamic acid derivatives as inhibitors of Bacillus cereus phosphatidylcholine preferred phospholipase C PC-PLCBc

  摘要：

  Phosphatidylcholine preferring phospholipase C (PC-PLC) is an important enzyme that plays a key role in a variety of cellular events and lipid homoeostases. Bacillus cereus phospholipase C (PC-PLCBc) has antigenic similarity with the elusive mammalian PC-PLC, which has not thus far been isolated and purified. Therefore the discovery of inhibitors of PC-PLCBc is of current interest. Here, we describe the synthesis and biological evaluation of a new type of compounds inhibiting PC-PLCBc. These compounds have been designed by evolution of previously described 2-aminohydroxamic acid PC-PLCBc inhibitors that block the enzyme by coordination of the zinc active site atoms present in PC-PLCBc [Gonzalez-Roura, A.; Navarro, I.; Delgado, A.; Llebaria, A.; Casas, J. Angew. Chem. Int. Ed. 2004, 43, 862]. The new compounds maintain the zinc coordinating groups and possess an extra trimethylammonium function, linked to the hydroxyamide nitrogen by an alkyl chain, which is expected to mimic the trimethylammonium group of the phosphatidylcholine PC-PLCBc substrates. Some of the compounds described inhibit the enzyme with IC50's in the low micromolar range. Unexpectedly, the most potent inhibitors found are those that possess a trimethylammonium group but have chemically blocked the zinc coordinating functionalities. The results obtained suggest that PC-PLCBc inhibition is not due to the interaction of compounds with the phospholipase catalytic zinc atoms, but rather results from the inhibitor cationic group recognition by the PC-PLCBc amino acids involved in choline lipid binding. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.10.031
• 作为产物：
  描述：

  3-(N-(benzyloxy)-2-(tert-butyloxycarbonylamino)dodecanamido)-N,N,N-trimethylpropan-1-aminium iodide 在 甲醇 、 乙酰氯 作用下， 反应 2.0h， 以99%的产率得到1-((benzyloxy)(3-(trimethylammonio)propyl)amino)-1-oxododecan-2-aminium dichloride
  参考文献：
  名称：

  2-Aminohydroxamic acid derivatives as inhibitors of Bacillus cereus phosphatidylcholine preferred phospholipase C PC-PLCBc

  摘要：

  Phosphatidylcholine preferring phospholipase C (PC-PLC) is an important enzyme that plays a key role in a variety of cellular events and lipid homoeostases. Bacillus cereus phospholipase C (PC-PLCBc) has antigenic similarity with the elusive mammalian PC-PLC, which has not thus far been isolated and purified. Therefore the discovery of inhibitors of PC-PLCBc is of current interest. Here, we describe the synthesis and biological evaluation of a new type of compounds inhibiting PC-PLCBc. These compounds have been designed by evolution of previously described 2-aminohydroxamic acid PC-PLCBc inhibitors that block the enzyme by coordination of the zinc active site atoms present in PC-PLCBc [Gonzalez-Roura, A.; Navarro, I.; Delgado, A.; Llebaria, A.; Casas, J. Angew. Chem. Int. Ed. 2004, 43, 862]. The new compounds maintain the zinc coordinating groups and possess an extra trimethylammonium function, linked to the hydroxyamide nitrogen by an alkyl chain, which is expected to mimic the trimethylammonium group of the phosphatidylcholine PC-PLCBc substrates. Some of the compounds described inhibit the enzyme with IC50's in the low micromolar range. Unexpectedly, the most potent inhibitors found are those that possess a trimethylammonium group but have chemically blocked the zinc coordinating functionalities. The results obtained suggest that PC-PLCBc inhibition is not due to the interaction of compounds with the phospholipase catalytic zinc atoms, but rather results from the inhibitor cationic group recognition by the PC-PLCBc amino acids involved in choline lipid binding. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.10.031