[(2S,3R,4S)-1-benzoyl-2-(2-ethoxy-2-oxoethyl)-6-(3-hydroxypropoxy)-4-(quinoline-2-carbonylamino)-3,4-dihydro-2H-quinolin-3-yl] 4-phenylbenzoate | 1068149-42-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: [(2S,3R,4S)-1-benzoyl-2-(2-ethoxy-2-oxoethyl)-6-(3-hydroxypropoxy)-4-(quinoline-2-carbonylamino)-3,4-dihydro-2H-quinolin-3-yl] 4-phenylbenzoate
• CAS: 1068149-42-7
• 化学式: C₄₆H₄₁N₃O₈
• 分子量: 763.847
• InChiKey: VBUIOLPDUJRJIA-RXJPVNSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  57
• 可旋转键数：
  15
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  喹醛酰氯 、 (2S,3R,4S)-(9H-fluoren-9-yl)methyl 4-(allyloxycarbonylamino)-2-(2-ethoxy-2-oxoethyl)-3-hydroxy-6-(3-hydroxypropoxy)-3,4-dihydroquinoline-1(2H)-carboxylate 、 苯甲酰氯 、 4-苯基苯甲酸 生成 [(2S,3R,4S)-1-benzoyl-2-(2-ethoxy-2-oxoethyl)-6-(3-hydroxypropoxy)-4-(quinoline-2-carbonylamino)-3,4-dihydro-2H-quinolin-3-yl] 4-phenylbenzoate
  参考文献：
  名称：

  The discovery of small molecule chemical probes of Bcl-XL and Mcl-1

  摘要：

  A tetrahydroaminoquinoline-based library was generated with the goals of finding small molecule modulators of protein-protein interactions. Several library members as well as other related intermediates were tested for their ability to bind to Bcl-X(L) and Mcl-1 by in silico and (15)N NMR studies. The NMR study led to the identification of the tetrahydroaminoquinoline-based nude scaffold, 7 as a weak binder (K(d) = 200 mu M for Bcl-X(L) and K(d) = 300 mu M for Mcl-1) to both proteins. Using this scaffold as the starting material, we then synthesized a focused library of only 9 derivatives by applying the principles of a fragment-based approach. All these derivatives were then tested by NMR and this led to the discovery of a novel, small molecule (MIPRALDEN, 17) as a binder to Mcl-1 and Bcl-XL (K(D) = 25 and 70 mu M). This finding is novel because to our knowledge there are not many small molecules known in the literature that bind to Mcl-1. Crown Copyright (C) 2008 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.06.023

文献信息

• The discovery of small molecule chemical probes of Bcl-XL and Mcl-1
  作者：Michael Prakesch、Alexey Yu Denisov、Marwen Naim、Kalle Gehring、Prabhat Arya

  DOI：10.1016/j.bmc.2008.06.023

  日期：2008.8

  A tetrahydroaminoquinoline-based library was generated with the goals of finding small molecule modulators of protein-protein interactions. Several library members as well as other related intermediates were tested for their ability to bind to Bcl-X(L) and Mcl-1 by in silico and (15)N NMR studies. The NMR study led to the identification of the tetrahydroaminoquinoline-based nude scaffold, 7 as a weak binder (K(d) = 200 mu M for Bcl-X(L) and K(d) = 300 mu M for Mcl-1) to both proteins. Using this scaffold as the starting material, we then synthesized a focused library of only 9 derivatives by applying the principles of a fragment-based approach. All these derivatives were then tested by NMR and this led to the discovery of a novel, small molecule (MIPRALDEN, 17) as a binder to Mcl-1 and Bcl-XL (K(D) = 25 and 70 mu M). This finding is novel because to our knowledge there are not many small molecules known in the literature that bind to Mcl-1. Crown Copyright (C) 2008 Published by Elsevier Ltd. All rights reserved.