2-(7-氟-1H-吲哚-3-基)乙酸 | 170893-02-4

• 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
• 中文名称: 2-(7-氟-1H-吲哚-3-基)乙酸
• 中文别名: 7-氟-1H-吲哚-3-乙酸
• 英文名称: 7-fluoroindole-3-acetic acid
• 英文别名: 7-fluoroindol-3-ylacetic acid；2-(7-fluoro-1H-indol-3-yl)acetic acid
• CAS: 170893-02-4
• 化学式: C₁₀H₈FNO₂
• mdl: MFCD09954803
• 分子量: 193.177
• InChiKey: MXEHCUNCVQVBQL-UHFFFAOYSA-N

物化性质

• 沸点：
  417.9±30.0 °C(Predicted)
• 密度：
  1.446±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(7-氟-1H-吲哚-3-基)乙酸 在 selenium(IV) oxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 (6-fluoro-1H-benzo[d]imidazol-2-yl)(7-fluoro-1H-indol-3-yl)methanone
  参考文献：
  名称：

  From methylene bridged diindole to carbonyl linked benzimidazoleindole: Development of potent and metabolically stable PCSK9 modulators

  摘要：

  Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently validated therapeutic target for lowering low-density lipoprotein cholesterol (LDL-C). Through phenotypic screening, we previously discovered a class of small-molecules with a 2,3'-diindolymethane (DIM) skeleton that can decrease the expression of PCSK9. But these compounds have low potency and low metabolically stability. After performing structure-activity relationship (SAR) optimization by nitrogen scan, deuterium substitution and fluorine scan, we identified a series of much more potent and metabolically stable PCSK9 modulators. A preliminary in vivo pharmacokinetic study was performed for representative analogues difluorodiindolyketone (DFDIK) 12 and difluorobenzoimidazolylindolylketone (DFBIIK-1) 13. The in vitro metabolic stability correlate well with the in vivo data. The most potent compound 21 has the EC50 of 0.15 nM. Our SAR studies also indicated that the NH on the indole ring of 21 can tolerate more function groups, which may facilitate the mechanism of action studies and also allow further improvement of the pharmacological properties. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112678
• 作为产物：
  描述：

  7-氟吲哚 在 hydrazine hydrate 、 sodium hydroxide 作用下， 以 乙醚 、 乙二醇 为溶剂， 反应 10.0h， 生成 2-(7-氟-1H-吲哚-3-基)乙酸
  参考文献：
  名称：

  From methylene bridged diindole to carbonyl linked benzimidazoleindole: Development of potent and metabolically stable PCSK9 modulators

  摘要：

  Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently validated therapeutic target for lowering low-density lipoprotein cholesterol (LDL-C). Through phenotypic screening, we previously discovered a class of small-molecules with a 2,3'-diindolymethane (DIM) skeleton that can decrease the expression of PCSK9. But these compounds have low potency and low metabolically stability. After performing structure-activity relationship (SAR) optimization by nitrogen scan, deuterium substitution and fluorine scan, we identified a series of much more potent and metabolically stable PCSK9 modulators. A preliminary in vivo pharmacokinetic study was performed for representative analogues difluorodiindolyketone (DFDIK) 12 and difluorobenzoimidazolylindolylketone (DFBIIK-1) 13. The in vitro metabolic stability correlate well with the in vivo data. The most potent compound 21 has the EC50 of 0.15 nM. Our SAR studies also indicated that the NH on the indole ring of 21 can tolerate more function groups, which may facilitate the mechanism of action studies and also allow further improvement of the pharmacological properties. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112678

文献信息

• BENZOIMIDAZOLE INDOLYL METHANES AND METHODS OF USING THEM TO INHIBIT PCKS9 AND PCKS9-MEDIATED AILMENTS
  申请人：Wisconsin Alumni Research Foundation

  公开号：US20200262819A1

  公开（公告）日：2020-08-20

  Described are benzoimidazole indolyl methane compounds, pharmaceutical compositions containing them, and use of the compounds to inhibit PCSK9-mediated ailments. The compounds have the structure:

  描述了苯并咪唑吲哚甲烷化合物，含有它们的药物组合物，以及利用这些化合物抑制PCSK9介导的疾病。这些化合物具有以下结构：
• Indole-3-acetic acid derivatives
  申请人：Wardman Peter

  公开号：US20050203166A1

  公开（公告）日：2005-09-15

  Compounds of formula (I), or physiologically functional derivatives thereof, wherein: R 1 , R 2 , R 3 and R′ 3 are independently selected from H or lower alkyl; and R 4 , R 5 , R 6 and R 7 are independently selected from H, electron withdrawing groups (such as F, Cl, Br, I, OCF 3 , carboxyl groups, acetal groups, electron deficient aryl groups), lower alkyl groups, lower alkoxy groups, aryl groups or aryloxy groups, wherein at least one of R 4 , R 5 , R 6 and R 7 is selected from an electron withdrawing group, may be used in methods of therapy, particular in treating neoplastic diseases in methods of GDEPT, ADPET, PDEPT and PDT.

  式（I）的化合物或其生理功能衍生物，其中：R1、R2、R3和R′3独立地选自H或较低的烷基；以及R4、R5、R6和R7独立地选自H、电子提取基团（如F、Cl、Br、I、OCF3、羧基、缩醛基、电子亏缺芳基）、较低的烷基、较低的烷氧基、芳基或芳氧基，其中R4、R5、R6和R7中至少有一个选自电子提取基团，可用于治疗方法，特别是在GDEPT、ADPET、PDEPT和PDT方法中用于治疗肿瘤性疾病。
• Effect of halogen substitution of indole-3-acetic acid on biological activity in pea fruit
  作者：Dennis M. Reinecke、Jocelyn A. Ozga、Volker Magnus

  DOI：10.1016/0031-9422(95)00367-g

  日期：1995.11

  all plants) have been implicated in fruit growth of pea. Pea ( Pisum sativum L.) fruit contain the auxins indole-3-acetic acid (IAA) and 4-chloroindole-3-acetic acid (4-C1-IAA). Fruits grow poorly and subsequently abscise when seeds are removed two days after anthesis, but 4-C1-IAA can substitute for the seeds in maintaining growth of deseeded fruit (pericarp) in planta . Applications of 4-C1-IAA promoted

  摘要 生长素（一类天然存在于所有植物中的植物生长激素）与豌豆的果实生长有关。豌豆 (Pisum sativum L.) 果实含有生长素吲哚-3-乙酸 (IAA) 和 4-氯吲哚-3-乙酸 (4-C1-IAA)。开花后两天取出种子时，果实生长不良并随后脱落，但 4-C1-IAA 可以替代种子以维持植物中去籽果实（果皮）的生长。4-C1-IAA 的应用促进了果皮生长，效果随着浓度从 1 到 100 μM 而增加，但当从 0.1 到 100 μM 测试时，IAA 对刺激生长无效。通过测定 4-、5-、6- 和 7-氯和氟取代的 IAA 的活性来检查卤素位置对果皮生长的影响。卤素的位置和类型极大地影响了生长素的活性，天然产物 4-C1-IAA 最为有效。在测试的其他化合物中，只有 5-C1-IAA 刺激豌豆果皮伸长，然后只是适度刺激。氟代 IAA 不刺激果皮生长，4-F-IAA 具有抑制作用。这项研究的独特之处在于它报告了
• Indole-3-Acetamido-Polyamines as Antimicrobial Agents and Antibiotic Adjuvants
  作者：Kenneth Sue、Melissa M. Cadelis、Evangelene S. Gill、Florent Rouvier、Marie-Lise Bourguet-Kondracki、Jean Michel Brunel、Brent R. Copp

  DOI：10.3390/biom13081226

  日期：——

  The widespread incidence of antimicrobial resistance necessitates the discovery of new classes of antimicrobials as well as adjuvant molecules that can restore the action of ineffective antibiotics. Herein, we report the synthesis of a new class of indole-3-acetamido-polyamine conjugates that were evaluated for antimicrobial activities against a panel of bacteria and two fungi, and for the ability to enhance the action of doxycycline against Pseudomonas aeruginosa and erythromycin against Escherichia coli. Compounds 14b, 15b, 17c, 18a, 18b, 18d, 19b, 19e, 20c and 20d exhibited strong growth inhibition of methicillin-resistant Staphylococcus aureus (MRSA) and Cryptococcus neoformans, with minimum inhibitory concentrations (MIC) typically less than 0.2 µM. Four analogues, including a 5-bromo 15c and three 5-methoxyls 16d–f, also exhibited intrinsic activity towards E. coli. Antibiotic kill curve analysis of 15c identified it to be a bactericide. While only one derivative was found to (weakly) enhance the action of erythromycin against E. coli, three examples, including 15c, were found to be strong enhancers of the antibiotic action of doxycycline against P. aeruginosa. Collectively, these results highlight the promising potential of α,ω-disubstituted indole-3-acetamido polyamine conjugates as antimicrobials and antibiotic adjuvants.

  由于抗菌药耐药性的广泛存在，因此有必要发现新的抗菌药类别以及能够恢复无效抗生素作用的辅助分子。在此，我们报告了一类新的吲哚-3-乙酰胺基多胺共轭物的合成，并评估了它们对一系列细菌和两种真菌的抗菌活性，以及增强强力霉素对绿脓杆菌和红霉素对大肠杆菌作用的能力。化合物 14b、15b、17c、18a、18b、18d、19b、19e、20c 和 20d 对耐甲氧西林金黄色葡萄球菌（MRSA）和新型隐球菌具有很强的生长抑制作用，最低抑制浓度（MIC）通常低于 0.2 µM。四种类似物，包括一种 5-溴 15c 和三种 5-甲氧基 16d-f，对大肠杆菌也具有内在活性。15c 的抗生素杀灭曲线分析表明它是一种杀菌剂。虽然只有一种衍生物被发现能（弱）增强红霉素对大肠杆菌的作用，但包括 15c 在内的三种衍生物被发现能强烈增强强力霉素对绿脓杆菌的抗生素作用。总之，这些结果凸显了α,ω-二取代吲哚-3-乙酰胺基多胺共轭物作为抗菌剂和抗生素佐剂的巨大潜力。
• Applying deep learning to iterative screening of medium-sized molecules for protein–protein interaction-targeted drug discovery
  作者：Yugo Shimizu、Tomoki Yonezawa、Yu Bao、Junichi Sakamoto、Mariko Yokogawa、Toshio Furuya、Masanori Osawa、Kazuyoshi Ikeda

  DOI：10.1039/d3cc01283b

  日期：——

  Updating predicting models could greatly improve the hit rate of virtual screening for identifying Keap1/Nrf2 protein–protein interaction inhibitors.

  更新预测模型可以大大提高虚拟筛选的命中率，从而确定 Keap1/Nrf2 蛋白-蛋白相互作用抑制剂。