1-(4-fluorophenyl)-3-(4-piperdinyl)-1H-indole | 769089-25-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-(4-fluorophenyl)-3-(4-piperdinyl)-1H-indole
• 英文别名: 1-(4-Fluorophenyl)-3-piperidin-4-ylindole
• CAS: 769089-25-0
• 化学式: C₁₉H₁₉FN₂
• 分子量: 294.372
• InChiKey: ZTUYBGQPNCPNCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  17
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-3-(4-piperdinyl)-1H-indole 在 sodium cyanoborohydride 、 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， 生成 1-(2-{4-[1-(4-Fluoro-phenyl)-2,3-dihydro-1H-indol-3-yl]-piperidin-1-yl}-ethyl)-imidazolidin-2-one
  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：

  对溴氟苯 在 platinum on activated charcoal 盐酸 、 copper bronze 、 氢气 、 potassium carbonate 、 溶剂黄146 、 三氟乙酸 、 copper(I) bromide 作用下， 反应 2.0h， 生成 1-(4-fluorophenyl)-3-(4-piperdinyl)-1H-indole
  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

• Noncataleptogenic, centrally acting dopamine D-2 and serotonin 5-HT2 antagonists within a series of 3-substituted 1-(4-fluorophenyl)-1H-indoles
  作者：Jens Perregaard、Joern Arnt、Klaus P. Boegesoe、John Hyttel、Connie Sanchez

  DOI：10.1021/jm00084a014

  日期：1992.3

  antagonism. Piperazinyl and tetrahydropyridyl indoles were cataleptogenic, while piperidyl substituted indoles surprisingly were found to be noncataleptogenic or only weakly cataleptogenic. Noncataleptogenic piperidyl derivatives also failed to block dopaminergic-mediated stereotypies, that is methyl phenidate-induced gnawing behavior in mice. These profiles resemble that of the atypical neuroleptic clozapine

  合成了一系列在3-位被1-哌嗪基，1,2,3,6-四氢-4-吡啶基和4-哌啶基取代的1-（4-氟苯基）-1H-吲哚。在所有三个亚系列中，在配体结合研究中发现了有效的多巴胺D-2和5-羟色胺5-HT2受体亲和力。作为对中枢5-HT 2受体拮抗作用的量度，大多数衍生物抑制了奎帕嗪诱导的大鼠头部抽搐。哌嗪基和四氢吡啶基吲哚是致肽原的，而哌啶基取代的吲哚令人惊讶地被发现是非致肽原的或仅是弱致肽原的。非致死因的哌啶基衍生物也未能阻止多巴胺能介导的定型观念，即哌醋甲酯诱导的小鼠行为。这些特征类似于非典型的精神抑制药氯氮平的特征。为了避免僵直，发现1-乙基-2-咪唑啉酮是碱性氮原子的最佳取代基。非典型的抗精神病药1- [2- [4- [5-氯-1-（4-氟苯基）-1H-吲哚-3-基] -1-哌啶基]乙基] -2-咪唑啉酮（sertindole，化合物14c）为这些结构/活性研究的结果，选择了进一步开发。
• Identification and synthesis of impurities formed during sertindole preparation
  作者：I V Sunil Kumar、G S R Anjaneyulu、V Hima Bindu

  DOI：10.3762/bjoc.7.5

  日期：——

  Sertindole (1), an atypical anti-psychotic drug is used for the treatment of schizophrenia. During the laboratory optimization and later during its bulk synthesis the formation of various impurities was observed. The impurities formed were monitored and their structures were tentatively assigned on the basis of their fragmentation patterns in LC-MS. Most of the impurities were synthesized and their assigned constitutions confirmed by co-injection in HPLC. We describe herein the formation, synthesis and characterization of these impurities. Our study will be of immense help to others to obtain chemically pure sertindole.

  Sertindole（1），一种非典型抗精神病药物，用于治疗精神分裂症。在实验室优化和后来的批量合成过程中，观察到了各种杂质的形成。这些杂质的形成得到了监测，并根据它们在LC-MS中的碎片图谱初步确定了它们的结构。大多数杂质已经合成，并通过HPLC共注射确认了它们的构成。我们在此描述了这些杂质的形成、合成和表征。我们的研究将对他人获得化学纯净的Sertindole有巨大的帮助。