1-(4-trifluoromethylbenzyl)-1H-indole-2-carboxylic acid | 866235-95-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(4-trifluoromethylbenzyl)-1H-indole-2-carboxylic acid
• 英文别名: 1-[[4-(trifluoromethyl)phenyl]methyl]indole-2-carboxylic acid
• CAS: 866235-95-2
• 化学式: C₁₇H₁₂F₃NO₂
• 分子量: 319.283
• InChiKey: MREVINRUMNIXFY-UHFFFAOYSA-N

物化性质

• 沸点：
  490.7±45.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-trifluoromethylbenzyl)-1H-indole-2-carboxylic acid 在 盐酸 、 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 3.0h， 生成 1-(4-trifluoromethylbenzyl)-indoline-2-imminium chloride
  参考文献：
  名称：

  Identification of indole scaffold-based dual inhibitors of NOD1 and NOD2

  摘要：

  NOD1 and NOD2 are important members of the pattern recognition receptor family and play a crucial role within the context of innate immunity. However, overactivation of NODs, especially of NOD1, has also been implicated in a number of diseases. Surprisingly, NOD1 remains a virtually unexploited target in this respect. To gain additional insight into the structure-activity relationships of NOD1 inhibitors, a series of novel analogs has been designed and synthesized and then screened for their NOD1-inhibitory activity. Selected compounds were also investigated for their NOD2-inhibitory activity. Two compounds 4 and 15, were identified as potent mixed inhibitors of NOD1 and NOD2, displaying a balanced inhibitory activity on both targets in the low micromolar range. The results obtained have enabled a deeper understanding of the structural requirements for NOD1 and NOD2 inhibition. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.08.044
• 作为产物：
  描述：

  吲哚-2-羧酸乙酯 在 氢氧化钾 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(4-trifluoromethylbenzyl)-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-γ binding agents with potential application to the treatment of osteoporosis

  摘要：

  The synthesis and structure-activity relationships of a novel series of N-sulfonyl-2-indole carboxamides that bind to peroxisome proliferator-activated receptor gamma (PPAR-gamma) are reported. Chemical optimization of the series led to the identification of 4q (IC(50)=50 nM) as a potent binding agent of PPAR-gamma. Also reported is preliminary cell based data suggesting the use of these compounds in the treatment of osteoporosis.

  DOI：

  10.1016/j.bmcl.2006.08.003

文献信息

• PHARMACEUTICAL COMPOSITION AND METHOD
  申请人：Slade Rachel M.

  公开号：US20090155903A1

  公开（公告）日：2009-06-18

  The invention provides compounds, pharmaceutical compositions and methods for the therapeutic treatment and prevention of neurodegenerative disorder and other Aβ 42 -related diseases and disorders.

  该发明提供了化合物、制药组合物和方法，用于治疗和预防神经退行性疾病和其他与Aβ42相关的疾病和障碍。
• Design, synthesis, and biological evaluation of dual-target COX-2/5-LOX inhibitors for the treatment of inflammation
  作者：Le Du、Shuaishuai Du、Jiaming Li、Hongwei Wang

  DOI：10.1007/s00044-022-02995-8

  日期：2023.2

  benzoic acid analogues as dual COX-2 / 5-LOX inhibitors and evaluated their anti-inflammatory properties in vivo. Compounds 7f and 7n showed significant anti-inflammatory activity in a xylene-induced mouse model of auricular edema. Furthermore, 7f and 7n exhibited moderate COX-2 inhibitory activity (IC50 = 537 and 321.5 nM) than celecoxib (IC50 = 10.04 nM) in vitro, among which 7n had higher COX-2 selectivity

  花生四烯酸代谢酶环氧合酶-2（COX-2）和5-脂氧合酶（5-LOX）被认为与包括炎症在内的多种疾病的发生和发展有关。与经典的 NSAIDs 相比，双重 COX-2/5-LOX 抑制是设计具有更有效生物活性、更少副作用和更广泛抗炎谱的化合物的有效策略。在这项研究中，我们设计并合成了一系列新型吲哚和吲唑芳基酰胺苯甲酸类似物作为双重 COX-2 / 5-LOX 抑制剂，并评估了它们的体内抗炎特性。化合物7f和7n在二甲苯诱导的耳水肿小鼠模型中显示出显着的抗炎活性。此外，7f和7n在体外表现出比塞来昔布 (IC 50 = 10.04 nM)适度的 COX-2 抑制活性 (IC 50  = 537 和 321.5 nM)  ，其中7n具有更高的 COX-2 选择性活性 (选择性指数 (COX-1/COX- 2) = 7.89) 和中度 5-LOX 抑制活性 (IC 50  = 222.1 nM)。与齐留通
• Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-γ binding agents with potential application to the treatment of osteoporosis
  作者：Corey R. Hopkins、Steven V. O’Neil、Michael C. Laufersweiler、Yili Wang、Matthew Pokross、Marlene Mekel、Artem Evdokimov、Richard Walter、Maria Kontoyianni、Maria E. Petrey、Georgios Sabatakos、Jeff T. Roesgen、Eloise Richardson、Thomas P. Demuth

  DOI：10.1016/j.bmcl.2006.08.003

  日期：2006.11

  The synthesis and structure-activity relationships of a novel series of N-sulfonyl-2-indole carboxamides that bind to peroxisome proliferator-activated receptor gamma (PPAR-gamma) are reported. Chemical optimization of the series led to the identification of 4q (IC(50)=50 nM) as a potent binding agent of PPAR-gamma. Also reported is preliminary cell based data suggesting the use of these compounds in the treatment of osteoporosis.
• [EN] COMPOUNDS FOR NEURODEGENERATIVE DISORDERS<br/>[FR] COMPOSES DESTINES AUX TROUBLES NEURODEGENERATIFS
  申请人：MYRIAD GENETICS INC

  公开号：WO2005092062A2

  公开（公告）日：2005-10-06

  The invention provides compounds, pharmaceutical compositions and methods for the therapeutic treatment and prevention of neurodegenerative disorders and other Aβ42-related diseases and disorders.
• Identification of indole scaffold-based dual inhibitors of NOD1 and NOD2
  作者：Kaja Keček Plešec、Dunja Urbančič、Martina Gobec、Aleksandra Pekošak、Tihomir Tomašič、Marko Anderluh、Irena Mlinarič-Raščan、Žiga Jakopin

  DOI：10.1016/j.bmc.2016.08.044

  日期：2016.11

  NOD1 and NOD2 are important members of the pattern recognition receptor family and play a crucial role within the context of innate immunity. However, overactivation of NODs, especially of NOD1, has also been implicated in a number of diseases. Surprisingly, NOD1 remains a virtually unexploited target in this respect. To gain additional insight into the structure-activity relationships of NOD1 inhibitors, a series of novel analogs has been designed and synthesized and then screened for their NOD1-inhibitory activity. Selected compounds were also investigated for their NOD2-inhibitory activity. Two compounds 4 and 15, were identified as potent mixed inhibitors of NOD1 and NOD2, displaying a balanced inhibitory activity on both targets in the low micromolar range. The results obtained have enabled a deeper understanding of the structural requirements for NOD1 and NOD2 inhibition. (C) 2016 Elsevier Ltd. All rights reserved.