[4-(5-Chloro-3-{1-[2-(2-oxo-imidazolidin-1-yl)-ethyl]-piperidin-4-yl}-indol-1-yl)-phenyl]-acetic acid methyl ester | 572913-79-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: [4-(5-Chloro-3-{1-[2-(2-oxo-imidazolidin-1-yl)-ethyl]-piperidin-4-yl}-indol-1-yl)-phenyl]-acetic acid methyl ester
• 英文别名: methyl 2-[4-[5-chloro-3-[1-[2-(2-oxoimidazolidin-1-yl)ethyl]piperidin-4-yl]indol-1-yl]phenyl]acetate
• CAS: 572913-79-2
• 化学式: C₂₇H₃₁ClN₄O₃
• 分子量: 495.021
• InChiKey: IKIDYUZRZURTHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [4-(5-Chloro-3-{1-[2-(2-oxo-imidazolidin-1-yl)-ethyl]-piperidin-4-yl}-indol-1-yl)-phenyl]-acetic acid methyl ester 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 生成 [4-(5-Chloro-3-{1-[2-(2-oxo-imidazolidin-1-yl)-ethyl]-piperidin-4-yl}-indol-1-yl)-phenyl]-acetic acid
  参考文献：
  名称：

  Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches

  摘要：

  A data set consisting of twenty-two sertindole analogues and ten structurally diverse inhibitors, spanning a wide range in potency, was analyzed using CoMSiA. A homology model of HERG was constructed from the crystal structure of the open MthK potassium channel. A complementary relationship between our CoMSiA and homology models is apparent when the long inhibitor axis is oriented parallel to the longitudinal axis of the pore, with the tail region pointed toward the selectivity filter. The key elements of the pharmacophore, the CoMSiA and the homology model are: (1) The hydrophobic feature optimally consists of an aromatic group that is capable of engaging in pi-stacking with a Phe656 side chain. Optionally, a second aromatic or hydrophobic group present in some inhibitors may contact an additional Phe656 side chain. (2) The basic nitrogen appears to undergo a pi-cation interaction with Tyr652. (3) The pore diameter (12Angstrom +), and depth of the selectivity loop relative to the intracellular opening, act as constraints on the conformation-dependent inhibitor dimensions. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00196-3
• 作为产物：
  描述：

  4-哌啶酮 在 platinum on activated charcoal 盐酸 、 氢气 、 potassium carbonate 、 溶剂黄146 、 三氟乙酸 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 [4-(5-Chloro-3-{1-[2-(2-oxo-imidazolidin-1-yl)-ethyl]-piperidin-4-yl}-indol-1-yl)-phenyl]-acetic acid methyl ester
  参考文献：
  名称：

  Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches

  摘要：

  A data set consisting of twenty-two sertindole analogues and ten structurally diverse inhibitors, spanning a wide range in potency, was analyzed using CoMSiA. A homology model of HERG was constructed from the crystal structure of the open MthK potassium channel. A complementary relationship between our CoMSiA and homology models is apparent when the long inhibitor axis is oriented parallel to the longitudinal axis of the pore, with the tail region pointed toward the selectivity filter. The key elements of the pharmacophore, the CoMSiA and the homology model are: (1) The hydrophobic feature optimally consists of an aromatic group that is capable of engaging in pi-stacking with a Phe656 side chain. Optionally, a second aromatic or hydrophobic group present in some inhibitors may contact an additional Phe656 side chain. (2) The basic nitrogen appears to undergo a pi-cation interaction with Tyr652. (3) The pore diameter (12Angstrom +), and depth of the selectivity loop relative to the intracellular opening, act as constraints on the conformation-dependent inhibitor dimensions. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00196-3

文献信息

• Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches
  作者：Robert A Pearlstein、Roy J Vaz、Jiesheng Kang、Xiao-Liang Chen、Maria Preobrazhenskaya、Andrey E Shchekotikhin、Alexander M Korolev、Ludmila N Lysenkova、Olga V Miroshnikova、James Hendrix、David Rampe

  DOI：10.1016/s0960-894x(03)00196-3

  日期：2003.5

  A data set consisting of twenty-two sertindole analogues and ten structurally diverse inhibitors, spanning a wide range in potency, was analyzed using CoMSiA. A homology model of HERG was constructed from the crystal structure of the open MthK potassium channel. A complementary relationship between our CoMSiA and homology models is apparent when the long inhibitor axis is oriented parallel to the longitudinal axis of the pore, with the tail region pointed toward the selectivity filter. The key elements of the pharmacophore, the CoMSiA and the homology model are: (1) The hydrophobic feature optimally consists of an aromatic group that is capable of engaging in pi-stacking with a Phe656 side chain. Optionally, a second aromatic or hydrophobic group present in some inhibitors may contact an additional Phe656 side chain. (2) The basic nitrogen appears to undergo a pi-cation interaction with Tyr652. (3) The pore diameter (12Angstrom +), and depth of the selectivity loop relative to the intracellular opening, act as constraints on the conformation-dependent inhibitor dimensions. (C) 2003 Elsevier Science Ltd. All rights reserved.