methyl 2-(4-chlorophenyl)-3-cyclohexyl-1H-indole-6-carboxylate | 774214-18-5

• 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: methyl 2-(4-chlorophenyl)-3-cyclohexyl-1H-indole-6-carboxylate
• CAS: 774214-18-5
• 化学式: C₂₂H₂₂ClNO₂
• 分子量: 367.875
• InChiKey: FDDHGXILKYARQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-chlorophenyl)-3-cyclohexyl-1H-indole-6-carboxylate 在 PS-carbodiimide resin 、 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 43.0h， 生成
  参考文献：
  名称：

  Potent Inhibitors of Subgenomic Hepatitis C Virus RNA Replication through Optimization of Indole-N-Acetamide Allosteric Inhibitors of the Viral NS5B Polymerase

  摘要：

  Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. Compounds that block replication of subgenomic HCV RNA in liver cells are of interest because of their demonstrated antiviral effect in the clinic. In followup to our recent report that indole-N-acetamides (e.g., 1) are potent allosteric inhibitors of the HCV NS513 polymerase enzyme, we describe here their optimization as cell-based inhibitors. The crystal structure of 1 bound to NS513 was a guide in the design of a two-dimensional compound array that highlighted that formally zwitterionic inhibitors have strong intracellular potency and that pregnane X receptor (PXR) activation (an undesired off-target activity) is linked to a structural feature of the inhibitor. Optimized analogues devoid of PXR activation (e.g., 55, EC50 = 127 nM) retain strong cell-based efficacy under high serum conditions and show acceptable pharmacokinetics parameters in rat and dog.

  DOI：

  10.1021/jm050056+
• 作为产物：
  描述：

  2-溴-3-环己基-1H-吲哚-6-羧酸甲酯 、 4-氯苯硼酸 在 四(三苯基膦)钯 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 4.0h， 以86%的产率得到methyl 2-(4-chlorophenyl)-3-cyclohexyl-1H-indole-6-carboxylate
  参考文献：
  名称：

  [EN] INDOLE ACETAMIDES AS INHIBITORS OF THE HEPATITIS C VIRUS NS5B POLYMERASE
  [FR] ACETAMIDES D'INDOLE COMME INHIBITEURS DE LA POLYMERASE NS5B DU VIRUS DE L'HEPATITE C

  摘要：

  本发明涉及式(I)的吲哚和氮杂吲哚化合物：其中X1、X2、X3、X4、A1、Ar1、R1、R2和n的定义如本文所述，以及其药用盐，用于预防和治疗丙型肝炎感染。

  公开号：

  WO2004087714A1

文献信息

• Indole acetamides as inhibitors of the hepatitis c virus ns5b polymerase
  申请人：Avolio Salvatore

  公开号：US20070167447A1

  公开（公告）日：2007-07-19

  The present invention relates to indole and azaindole compounds of formula (I): wherein X 1 , X 2 , X 3 , X 4 , A 1 , Ar 1 , R 1 , R 2 and n are as defined herein, and pharmaceutically acceptable salts thereof, useful in the prevention and treatment of hepatitis C infections.

  本发明涉及式(I)的吲哚和氮杂吲哚化合物：其中X1，X2，X3，X4，A1，Ar1，R1，R2和n如本文所定义，并且其药学上可接受的盐，在预防和治疗丙型肝炎感染方面有用。
• Finger-loop inhibitors of the HCV NS5b polymerase. Part 1: Discovery and optimization of novel 1,6- and 2,6-macrocyclic indole series
  作者：David McGowan、Sandrine Vendeville、Tse-I Lin、Abdellah Tahri、Lili Hu、Maxwell D. Cummings、Katie Amssoms、Jan Martin Berke、Maxime Canard、Erna Cleiren、Pascale Dehertogh、Stefaan Last、Els Fransen、Elisabeth Van Der Helm、Iris Van den Steen、Leen Vijgen、Marie-Claude Rouan、Gregory Fanning、Origène Nyanguile、Kristof Van Emelen、Kenneth Simmen、Pierre Raboisson

  DOI：10.1016/j.bmcl.2012.03.097

  日期：2012.7

  Novel conformationaly constrained 1,6- and 2,6-macrocyclic HCV NS5b polymerase inhibitors, in which either the nitrogen or the phenyl ring in the C2 position of the central indole core is tethered to an acylsulfamide acid bioisostere, have been designed and tested for their anti-HCV potency. This transformational route toward non-zwitterionic finger loop-directed inhibitors led to the discovery of derivatives with improved cell potency and pharmacokinetic profile. (C) 2012 Elsevier Ltd. All rights reserved.
• Development of carboxylic acid replacements in indole-N-acetamide inhibitors of hepatitis C virus NS5B polymerase
  作者：Ian Stansfield、Marco Pompei、Immacolata Conte、Caterina Ercolani、Giovanni Migliaccio、Mark Jairaj、Claudio Giuliano、Michael Rowley、Frank Narjes

  DOI：10.1016/j.bmcl.2007.06.093

  日期：2007.9

  Allosteric inhibition of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polyrnerase enzyme has recently emerged as a viable strategy toward blocking replication of viral RNA in cell-based systems. We report here 2 series of indole-N-acetamides, bearing physicochemically diverse carboxylic acid replacements, which show potent affinity for the NS5B enzyme with reduced potential for formation of glucuronide conjugates. Preliminary optimization of these series furnished compounds that are potent in the blockade of subgenomic HCV RNA replication in HUH-7 cells. (c) 2007 Elsevier Ltd. All rights reserved.
• EP1613634A1
  申请人：——

  公开号：EP1613634A1

  公开（公告）日：2006-01-11