methyl 3-benzoyl-1H-indole-5-carboxylate | 953029-86-2

• 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: methyl 3-benzoyl-1H-indole-5-carboxylate
• 英文别名: 3-Benzoyl-1H-indole-5-carboxylic acid methyl ester
• CAS: 953029-86-2
• 化学式: C₁₇H₁₃NO₃
• 分子量: 279.295
• InChiKey: FCQQGWQUNUQXJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-benzoyl-1H-indole-5-carboxylate 在 sodium hydride 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 5.0h， 生成 3‐benzoyl‐N‐[2‐(1H‐imidazol‐5‐yl)ethyl]‐1‐methyl‐1H‐indole‐5‐carboxamide
  参考文献：
  名称：

  The azulene scaffold from a medicinal chemist's perspective: Physicochemical and in vitro parameters relevant for drug discovery

  摘要：

  DOI：

  10.1016/j.ejmech.2022.114374
• 作为产物：
  描述：

  苯甲酰氯 、 吲哚-5-甲酸甲酯 在 四氯化锡 作用下， 以 甲苯 为溶剂， 生成 methyl 3-benzoyl-1H-indole-5-carboxylate
  参考文献：
  名称：

  Palladium-Catalyzed Weak-Chelation-Assisted C4-Nitration of Indoles with tert-Butyl Nitrite: Formal Access to Aminated Indoles

  摘要：

  DOI：

  10.1021/acs.orglett.3c03921

文献信息

• Structure–Activity Relationships of 1‐Benzoylazulenes at the OX ₁ and OX ₂ Orexin Receptors
  作者：Ainoleena Turku、Teppo O. Leino、Lasse Karhu、Jari Yli‐Kauhaluoma、Jyrki P. Kukkonen、Erik A. A. Wallén、Henri Xhaard

  DOI：10.1002/cmdc.201900074

  日期：2019.5.6

  receptor agonists. For potentiators, replacement of the azulene scaffold by indole retained the activity of four out of six compounds. The structure-activity relationships for agonism and potentiation can be summarized into a bicyclic aromatic ring system substituted with two hydrogen-bond acceptors (1-position, benzoyl; 6-position, carboxyl/ester) within 7-8 Å of each other; a third acceptor at the 3-position

  先前我们证明了二或三取代的天青石作为orexin受体的配体（增强剂，弱激动剂和拮抗剂）的潜力。在这项研究中，我们研究了27种1-苯甲酰基azulene衍生物，揭示了ox1对orexin反应的7种增强剂和2种弱双orexin受体激动剂。对于增效剂，用吲哚代替the唑骨架保留了六种化合物中四种的活性。激动和增强作用的构效关系可以概括为一个双环芳香环系统，该系统被两个氢键受体（1-位，苯甲酰基； 6-位，羧基/酯）相互取代，彼此之间的距离为7-8；在3位的第三个受体也被很好地耐受。从分子动力学模拟中，在orexin受体激动剂Nag26的优选构象中发现了相同的药效学特征。细微的变化在弱激动和增强之间切换活性，表明结合位点重叠。
• Inhibition of Shp2/PTPN11 Protein Tyrosine Phosphatase by NSC-87877, NSC-117199 and Their Analogs
  申请人：Wu Jie

  公开号：US20080176309A1

  公开（公告）日：2008-07-24

  Compounds and associated methods for inhibiting a protein tyrosine phosphatase. By a combination of experimental and virtual screenings of the NCI Diversity Set chemical library, NSC-87877 and NSC-117199 have been identified as Shp2 PTP inhibitors. Significantly, NSC-87877 is active in cell-based assays and has no detectable off-target effects in the EGF-stimulated Erk1/2 activation pathway. Additionally, a number of analogs of NSC-117199 have been produced. These analogs exhibit enhanced protein tyrosine phosphatase inhibition and are found to be potent and/or selective inhibitors of Shp1 and/or Shp2 protein tyrosine phosphatases.

  化合物及其相关方法，用于抑制蛋白酪氨酸磷酸酶。通过NCI Diversity Set化学库的实验和虚拟筛选的组合，已经确定NSC-87877和NSC-117199是Shp2 PTP抑制剂。值得注意的是，NSC-87877在基于细胞的实验中是活性的，并且在EGF刺激的Erk1/2激活途径中没有检测到任何非靶效应。此外，已经生产了许多NSC-117199的类似物。这些类似物表现出增强的蛋白酪氨酸磷酸酶抑制作用，并被发现是Shp1和/或Shp2蛋白酪氨酸磷酸酶的有效和/或选择性抑制剂。
• Inhibition of Shp2/PTPN11 protein tyrosine phosphatase by NSC-87877, NSC-117199 and their analogs
  申请人：Wu Jie

  公开号：US08987474B2

  公开（公告）日：2015-03-24

  Compounds and associated methods for inhibiting a protein tyrosine phosphatase. By a combination of experimental and virtual screenings of the NCI Diversity Set chemical library, NSC-87877 and NSC-117199 have been identified as Shp2 PTP inhibitors. Significantly, NSC-87877 is active in cell-based assays and has no detectable off-target effects in the EGF-stimulated Erk 1/2 activation pathway. Additionally, a number of analogs of NSC-117199 have been produced. These analogs exhibit enhanced protein tyrosine phosphatase inhibition and are found to be potent and/or selective inhibitors of Shp1 and/or Shp2 protein tyrosine phosphatases.

  化合物和相关方法用于抑制蛋白酪氨酸磷酸酶。通过实验和虚拟筛选NCI Diversity Set化学库，NSC-87877和NSC-117199已被确定为Shp2 PTP抑制剂。值得注意的是，NSC-87877在细胞基础实验中活性高，并且在EGF刺激的Erk 1/2激活途径中没有检测到离靶效应。此外，已经生产了一些NSC-117199的类似物。这些类似物表现出增强的蛋白酪氨酸磷酸酶抑制作用，并被发现是Shp1和/或Shp2蛋白酪氨酸磷酸酶的有效和/或选择性抑制剂。
• WO2007/117699
  申请人：——

  公开号：——

  公开（公告）日：——
• 1-(5-Carboxyindol-1-yl)propan-2-one Inhibitors of Human Cytosolic Phospholipase A₂α: Effect of Substituents in Position 3 of the Indole Scaffold on Inhibitory Potency, Metabolic Stability, Solubility, and Bioavailability
  作者：Stefanie Bovens、Alwine Schulze Elfringhoff、Martina Kaptur、Dirk Reinhardt、Michael Schäfers、Matthias Lehr

  DOI：10.1021/jm101094p

  日期：2010.12.9

  Indole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position I have been found to be potent inhibitors of human cytosolic phospholipase A(2)alpha (cPLA(2)alpha). In the course of structure-activity relationship studies, we investigated the effect of a substitution of indole 3 position with acyl, alkyl, and oxadiazole residues. The highest increase of inhibitory potency could be achieved by a 3-methyl-1,2, 4-oxadiazol-5-yl-moiety. Appropriate compound 40 revealed an IC50 of 0.0021 mu M against isolated cPLA(2)alpha. In a cellular assay applying human platelets 40 blocked cPLA(2)alpha. activity even with an IC50 of 0.0006 mu M. Metabolic stability and aqueous solubility of the target compounds were also determined. Furthermore, one selected compound was tested for peroral bioavailability in mice.