ethyl 3β-([D-tryptophanyl]oxy)-11-oxo-olean-12-en-30-oate | 1612838-66-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: ethyl 3β-([D-tryptophanyl]oxy)-11-oxo-olean-12-en-30-oate
• 英文别名: ethyl (2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-10-[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]oxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylate
• CAS: 1612838-66-0
• 化学式: C₄₃H₆₀N₂O₅
• 分子量: 684.96
• InChiKey: OSJQXWILHFFBDU-NPVIHDMJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  50
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl 3β-([boc-D-tryptophanyl]oxy)-11-oxo-olean-12-en-30-oate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以96%的产率得到ethyl 3β-([D-tryptophanyl]oxy)-11-oxo-olean-12-en-30-oate
  参考文献：
  名称：

  Amino derivatives of glycyrrhetinic acid as potential inhibitors of cholinesterases

  摘要：

  The development of remedies against the Alzheimer's disease (AD) is one of the biggest challenges in medicinal chemistry nowadays. Although not completely understood, there are several strategies fighting this disease or at least bringing some relief. During the progress of AD, the level of acetylcholine (ACh) decreases; hence, a therapy using inhibitors should be of some benefit to the patients. Drugs presently used for the treatment of AD inhibit the two ACh controlling enzymes, acetylcholinesterase as well as butyrylcholinesterase; hence, the design of selective inhibitors is called for. Glycyrrhetinic acid seems to be an interesting starting point for the development of selective inhibitors. Although its glycon, glycyrrhetinic acid is known for being an AChE activator, several derivatives, altered in position C-3 and C-30, exhibited remarkable inhibition constants in micro-molar range. Furthermore, five representative compounds were subjected to three more enzyme assays (on carbonic anhydrase II, papain and the lipase from Candida antarctica) to gain information about the selectivity of the compounds in comparison to other enzymes. In addition, photometric sulforhodamine B assays using murine embryonic fibroblasts (NiH 3T3) were performed to study the cytotoxicity of these compounds. Two derivatives, bearing either a 1,3-diaminopropyl or a 1H-benzotriazolyl residue, showed a BChE selective inhibition in the single-digit micro-molar range without being cytotoxic up to 30 mu M. In silica molecular docking studies on the active sites of AChE and BChE were performed to gain a molecular insight into the mode of action of these compounds and to explain the pronounced selectivity for BChE. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.046

文献信息

• Amino derivatives of glycyrrhetinic acid as potential inhibitors of cholinesterases
  作者：Stefan Schwarz、Susana Dias Lucas、Sven Sommerwerk、René Csuk

  DOI：10.1016/j.bmc.2014.04.046

  日期：2014.7

  The development of remedies against the Alzheimer's disease (AD) is one of the biggest challenges in medicinal chemistry nowadays. Although not completely understood, there are several strategies fighting this disease or at least bringing some relief. During the progress of AD, the level of acetylcholine (ACh) decreases; hence, a therapy using inhibitors should be of some benefit to the patients. Drugs presently used for the treatment of AD inhibit the two ACh controlling enzymes, acetylcholinesterase as well as butyrylcholinesterase; hence, the design of selective inhibitors is called for. Glycyrrhetinic acid seems to be an interesting starting point for the development of selective inhibitors. Although its glycon, glycyrrhetinic acid is known for being an AChE activator, several derivatives, altered in position C-3 and C-30, exhibited remarkable inhibition constants in micro-molar range. Furthermore, five representative compounds were subjected to three more enzyme assays (on carbonic anhydrase II, papain and the lipase from Candida antarctica) to gain information about the selectivity of the compounds in comparison to other enzymes. In addition, photometric sulforhodamine B assays using murine embryonic fibroblasts (NiH 3T3) were performed to study the cytotoxicity of these compounds. Two derivatives, bearing either a 1,3-diaminopropyl or a 1H-benzotriazolyl residue, showed a BChE selective inhibition in the single-digit micro-molar range without being cytotoxic up to 30 mu M. In silica molecular docking studies on the active sites of AChE and BChE were performed to gain a molecular insight into the mode of action of these compounds and to explain the pronounced selectivity for BChE. (C) 2014 Elsevier Ltd. All rights reserved.