4-(2-(1H-indol-1-yl)ethoxy)benzaldehyde | 205371-45-5

• 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: 4-(2-(1H-indol-1-yl)ethoxy)benzaldehyde
• 英文别名: 4-[2-(1-Indolyl)ethoxy]benzaldehyde；4-(2-indol-1-ylethoxy)benzaldehyde
• CAS: 205371-45-5
• 化学式: C₁₇H₁₅NO₂
• 分子量: 265.312
• InChiKey: JCBSYUJDDQWOKK-UHFFFAOYSA-N

物化性质

• 沸点：
  478.4±25.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(2-(1H-indol-1-yl)ethoxy)benzaldehyde 在 哌啶 、 sodium tetrahydroborate 、 cobalt dimethylglyoxime 、 苯甲酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 24.0h， 生成 5-[[4-(2-吲哚-1-基乙氧基)苯基]甲基]-1,3-噻唑烷-2,4-二酮
  参考文献：
  名称：

  Synthesis, biological evaluation, and molecular docking investigation of benzhydrol- and indole-based dual PPAR-γ/FFAR1 agonists

  摘要：

  Type-2 diabetes mellitus is a progressive cluster of metabolic disorders, representing a global public health burden affecting more than 366 million people worldwide. We recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome proliferator activated receptor-gamma (PPAR-gamma) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures. To further investigate this concept, two new scaffolds, the benzhydrol- and indole-based chemotypes, were introduced here in. Our optimization campaign resulted in three compounds; 15a, 15c, and 15d, with affinities in the low micromolar range on both targets. In vivo study of selected test compounds, revealed that 15c possesses a significant anti-hyperglycemic and anti-hyperlipidemic activities superior to rosiglitazone in fat-fed animal models. Molecular docking analysis was conducted to explain the binding modes of both series. These compounds could lead to the development of the unique antidiabetic agent acting as insulin sensitizer as well as insulin secretagogue. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.03.051
• 作为产物：
  描述：

  对羟基苯甲醛 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 potassium hydroxide 作用下， 以 四氢呋喃 、 二甲基亚砜 、 甲苯 为溶剂， 反应 0.5h， 生成 4-(2-(1H-indol-1-yl)ethoxy)benzaldehyde
  参考文献：
  名称：

  Synthesis, biological evaluation, and molecular docking investigation of benzhydrol- and indole-based dual PPAR-γ/FFAR1 agonists

  摘要：

  Type-2 diabetes mellitus is a progressive cluster of metabolic disorders, representing a global public health burden affecting more than 366 million people worldwide. We recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome proliferator activated receptor-gamma (PPAR-gamma) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures. To further investigate this concept, two new scaffolds, the benzhydrol- and indole-based chemotypes, were introduced here in. Our optimization campaign resulted in three compounds; 15a, 15c, and 15d, with affinities in the low micromolar range on both targets. In vivo study of selected test compounds, revealed that 15c possesses a significant anti-hyperglycemic and anti-hyperlipidemic activities superior to rosiglitazone in fat-fed animal models. Molecular docking analysis was conducted to explain the binding modes of both series. These compounds could lead to the development of the unique antidiabetic agent acting as insulin sensitizer as well as insulin secretagogue. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.03.051

文献信息

• Pheny (alkyl)carboxylic acid derivatives and dionic phenylalkylheterocyclic derivatives and their use as medicines with serum glucose and/or serum lipid lowering activity
  申请人：Giannessi Fabio

  公开号：US20050032787A1

  公开（公告）日：2005-02-10

  Formula (I) compounds are described: Where the groups are as defined here below, and their use as medinies, particularly as serum glucose and serum lipid lowering agents. Said medicines are useful for the prophylaxis and treatment of diabetes, particularly type 2, and its complications, Syndrome X, the various forms of insulin resistance, and hyperlipidaemias, and present reduced side effects, and, particularly, reduced or no liver toxicity.

  描述了公式(I)化合物：其中各组如下所定义，并且它们的用途作为药物，特别是作为血清葡萄糖和血清脂质降低剂。所述药物对于预防和治疗糖尿病，特别是2型糖尿病及其并发症，综合征X，各种形式的胰岛素抵抗和高脂血症非常有用，并且具有减少的副作用，特别是减少或无肝毒性。
• Novel Euglycemic and Hypolipidemic Agents. 1
  作者：Braj B. Lohray、Vidya Bhushan、Bheema P. Rao、Gurram R. Madhavan、Nagabelli Murali、Krovvidi N. Rao、Ananth K. Reddy、Bagepalli M. Rajesh、Pamulapati G. Reddy、Ranjan Chakrabarti、Reeba K. Vikramadithyan、Ramanujam Rajagopalan、Rao N. V. S. Mamidi、Hemant K. Jajoo、Swaminathan Subramaniam

  DOI：10.1021/jm970444e

  日期：1998.5.1

  A series of [[(heterocyclyl)ethoxy]benzyl]-2,4-thiazolidinediones have been synthesized by the condensation of corresponding aldehyde 1 and 2,4-thiazolidinedione followed by hydrogenation. Both unsaturated thiazolidinedione 2 and its saturated counterpart 3 have shown antihyperglycemic activity. Many of these compounds have shown superior euglycemic and hypolipidemic activity compared to troglitazone (CS 045). The indole analogue DRF-2189 (3g) was found to be a very potent insulin sensitizer, comparable to BRL-49653 in genetically obese C57BL/6J-ob/ob and 57BL/KsJ-db/db mice. Pharmacokinetic and tissue distribution studies conducted on BRL-49653 and DRF-2189 (3g) indicate that these drugs are well-distributed in target tissues. On the basis of euglycemic activity as well as enhanced selectivity against reduction of triglycerides in plasma, DRF-2189 (3g) has been selected for further evaluation.
• Novel indole containing thiazolidinedione derivatives as potent euglycemic and hypolipidaemic agents
  作者：Braj B. Lohray、V. Bhushan、P.Bheema Rao、G.R. Madhavan、N. Murali、K.Narasimha Rao、G.R. Madhavan、N. Murali、K.Narasimha Rao、K. Anantha Reddy、B.M. Rajesh、P. Ganpathy Reddy、R. Chakrabarti、R. Rajagopalan

  DOI：10.1016/s0960-894x(97)00118-2

  日期：1997.1

  Several thiazolidinediones having indol as heterocyclic moiety have been synthesized and evaluated for euglycemic properties. A few of them have been found to be superior to troglitazone. (C) 1997 Elsevier Science Ltd.
• Synthesis, biological evaluation, and molecular docking investigation of benzhydrol- and indole-based dual PPAR-γ/FFAR1 agonists
  作者：Khaled M. Darwish、Ismail Salama、Samia Mostafa、Mohamed S. Gomaa、El-Sayed Khafagy、Mohamed A. Helal

  DOI：10.1016/j.bmcl.2018.03.051

  日期：2018.5

  Type-2 diabetes mellitus is a progressive cluster of metabolic disorders, representing a global public health burden affecting more than 366 million people worldwide. We recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome proliferator activated receptor-gamma (PPAR-gamma) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures. To further investigate this concept, two new scaffolds, the benzhydrol- and indole-based chemotypes, were introduced here in. Our optimization campaign resulted in three compounds; 15a, 15c, and 15d, with affinities in the low micromolar range on both targets. In vivo study of selected test compounds, revealed that 15c possesses a significant anti-hyperglycemic and anti-hyperlipidemic activities superior to rosiglitazone in fat-fed animal models. Molecular docking analysis was conducted to explain the binding modes of both series. These compounds could lead to the development of the unique antidiabetic agent acting as insulin sensitizer as well as insulin secretagogue. (C) 2018 Elsevier Ltd. All rights reserved.