4-(1-(4-fluorophenyl)-1H-indol-3-yl)butanoic acid | 1533426-05-9

• 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-(1-(4-fluorophenyl)-1H-indol-3-yl)butanoic acid
• 英文别名: 4-[1-(4-Fluorophenyl)indol-3-yl]butanoic acid
• CAS: 1533426-05-9
• 化学式: C₁₈H₁₆FNO₂
• 分子量: 297.329
• InChiKey: KBHYMMADUMPBTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.18
• 重原子数：
  22.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  42.23
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  4-(1-(4-fluorophenyl)-1H-indol-3-yl)butanoic acid 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 2.0h， 以98%的产率得到4-<1-(4-fluorophenyl)-1H-indol-3-yl>-1-butanol
  参考文献：
  名称：

  Sigma-2受体激动剂可能是抗肿瘤药物的抗肿瘤药：对侧支敏感性的提示

  摘要：

  与促进新的抗肿瘤剂的开发为目标，高亲和力σ 2受体激动剂被开发，用6,7-二甲氧基-2- [4- [1-（4-氟苯基）-1- ħ吲哚-3- [-基]丁基] -1,2,3,4-四氢异喹啉（15）和9- [4-（6,7-二甲氧基-1,2,3,4-四氢异喹啉-2-基）丁基] -9 H -咔唑（25）示出了特殊的选择性为σ 2亚型。大多数化合物在人MCF7乳腺腺癌细胞中显示出显着的抗增殖活性，在相应的对阿霉素耐药的MCF7adr细胞系中也具有相似的活性。令人惊讶的是，其中一些化合物包括25种，显示MCF7adr细胞的活性比亲代细胞增强，回想起附带敏感性的现象，该现象正在研究中，用于治疗耐药性肿瘤。所有这些化合物均显示与P-糖蛋白（P-gp）相互作用，而15和25具有最大的活性，能够逆转P-gp介导的耐药性，并重新建立阿霉素在MCF7adr细胞中的抗肿瘤作用。因此，我们确定了一系列σ的2赋有耐人寻味抗肿瘤特性受体激动剂;

  DOI：

  10.1002/cmdc.201300291
• 作为产物：
  描述：

  3-吲哚丁酸 、 对氟碘苯 在 copper(l) iodide 、 potassium carbonate 作用下， 以 乙二醇乙醚 为溶剂， 反应 0.67h， 以50%的产率得到4-(1-(4-fluorophenyl)-1H-indol-3-yl)butanoic acid
  参考文献：
  名称：

  Sigma-2受体激动剂可能是抗肿瘤药物的抗肿瘤药：对侧支敏感性的提示

  摘要：

  与促进新的抗肿瘤剂的开发为目标，高亲和力σ 2受体激动剂被开发，用6,7-二甲氧基-2- [4- [1-（4-氟苯基）-1- ħ吲哚-3- [-基]丁基] -1,2,3,4-四氢异喹啉（15）和9- [4-（6,7-二甲氧基-1,2,3,4-四氢异喹啉-2-基）丁基] -9 H -咔唑（25）示出了特殊的选择性为σ 2亚型。大多数化合物在人MCF7乳腺腺癌细胞中显示出显着的抗增殖活性，在相应的对阿霉素耐药的MCF7adr细胞系中也具有相似的活性。令人惊讶的是，其中一些化合物包括25种，显示MCF7adr细胞的活性比亲代细胞增强，回想起附带敏感性的现象，该现象正在研究中，用于治疗耐药性肿瘤。所有这些化合物均显示与P-糖蛋白（P-gp）相互作用，而15和25具有最大的活性，能够逆转P-gp介导的耐药性，并重新建立阿霉素在MCF7adr细胞中的抗肿瘤作用。因此，我们确定了一系列σ的2赋有耐人寻味抗肿瘤特性受体激动剂;

  DOI：

  10.1002/cmdc.201300291

文献信息

• Potential applications for sigma receptor ligands in cancer diagnosis and therapy
  作者：Aren van Waarde、Anna A. Rybczynska、Nisha K. Ramakrishnan、Kiichi Ishiwata、Philip H. Elsinga、Rudi A.J.O. Dierckx

  DOI：10.1016/j.bbamem.2014.08.022

  日期：2015.10

  Sigma receptors (sigma-1 and sigma-2) represent two independent classes of proteins. Their endogenous ligands may include the hallucinogen N,N-dimethyltryptamine (DMT) and sphingolipid-derived amines which interact with sigma-1 receptors, besides steroid hormones (e.g., progesterone) which bind to both sigma receptor sub-populations. The sigma-1 receptor is a ligand-regulated molecular chaperone with various ion channels and G-protein-coupled membrane receptors as clients. The sigma-2 receptor was identified as the progesterone receptor membrane component 1 (PGRMC1). Although sigma receptors are over-expressed in tumors and up-regulated in rapidly dividing normal tissue, their ligands induce significant cell death only in tumor tissue. Sigma ligands may therefore be used to selectively eradicate tumors. Multiple mechanisms appear to underlie cell killing after administration of sigma ligands, and the signaling pathways are dependent both on the type of ligand and the type of tumor cell. Recent evidence suggests that the sigma-2 receptor is a potential tumor and serum biomarker for humaniung cancer and an important target for inhibiting tumor invasion and cancer progression. Current radiochemical efforts are focused on the development of subtype-selective radioligands for positron emission tomography (PET) imaging. Right now, the mostpromising tracers are [F-18]fluspidine and [F-18]FTC-146 for sigma-1 receptors and [C-11]RHM-1 and [F-18]ISO-1 for the sigma-2 subtype. Nanoparticles coupled to sigma ligands have shown considerable potential for targeted delivery of antitumor drugs in animal models of cancer, but clinical studies exploring this strategy in cancer patients have not yet been reported. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. (C) 2014 Elsevier B.V. All rights reserved.
• From mixed sigma-2 receptor/P-glycoprotein targeting agents to selective P-glycoprotein modulators: Small structural changes address the mechanism of interaction at the efflux pump
  作者：Carmen Abate、Maria Laura Pati、Marialessandra Contino、Nicola Antonio Colabufo、Roberto Perrone、Mauro Niso、Francesco Berardi

  DOI：10.1016/j.ejmech.2014.10.082

  日期：2015.1

  Generations of modulators of the efflux pump P-glycoprotein (P-gp) have been produced as tools to counteract the Multidrug Resistance (MDR) phenomenon in tumor therapy, but clinical trials were not successful so far. With the aim of contributing to the development of novel P-gp modulators, we started from recently studied high-affinity sigma-2 (sigma(2)) receptor ligands that showed also potent interaction with P-gp. For sigma(2) receptors high-affinity binding, a basic N-atom is a strict requirement. Therefore, we reduced the basic character of the N-atom present in these ligands, and we obtained potent P-gp modulators with poor or null sigma(2) receptor affinity. We also evaluated whether modulation of P-gp by these novel compounds involved consumption of ATP (as P-gp substrates do), as a source of energy to support the efflux. Surprisingly, even small structural changes resulted in opposite behavior, with amide 13 depleting ATP, in contrast to its isomer 18. Two compounds, 15 and 25, emerged for their potent activity at P-gp, and deserve further investigations as tools for P-gp modulation. (C) 2014 Elsevier Masson SAS. All rights reserved.