2-(3-环己基-6-甲氧基羰基-2-苯基吲哚-1-基)乙酸 | 774213-85-3

• 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-(3-环己基-6-甲氧基羰基-2-苯基吲哚-1-基)乙酸
• 英文名称: [3-cyclohexyl-6-(methoxycarbonyl)-2-phenyl-1H-indol-1-yl]acetic acid
• 英文别名: 2-(3-Cyclohexyl-6-(methoxycarbonyl)-2-phenyl-1H-indol-1-yl)acetic acid；2-(3-cyclohexyl-6-methoxycarbonyl-2-phenylindol-1-yl)acetic acid
• CAS: 774213-85-3
• 化学式: C₂₄H₂₅NO₄
• 分子量: 391.467
• InChiKey: XHLAADIRLVRSFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  68.5
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-(3-环己基-6-甲氧基羰基-2-苯基吲哚-1-基)乙酸 在 sodium hydroxide 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 16.0h， 生成 3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-phenyl-1H-indole-6-carboxylic acid
  参考文献：
  名称：

  Development of carboxylic acid replacements in indole-N-acetamide inhibitors of hepatitis C virus NS5B polymerase

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2007.06.093
• 作为产物：
  描述：

  3-环己基-1H-吲哚-6-羧酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 sodium hydride 、 sodium carbonate 、 三氟乙酸 作用下， 以 四氯化碳 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.5h， 生成 2-(3-环己基-6-甲氧基羰基-2-苯基吲哚-1-基)乙酸
  参考文献：
  名称：

  Development and Preliminary Optimization of Indole-N-Acetamide Inhibitors of Hepatitis C Virus NS5B Polymerase

  摘要：

  Allosteric inhibition of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase enzyme has recently emerged as a viable strategy toward blocking replication of viral RNA in cell-based systems. We report here a novel class of allosteric inhibitor of NS5B that shows potent affinity for the NS5B enzyme and effective inhibition of subgenomic HCV RNA replication in HUH-7 cells. Inhibitors from this class have promising characteristics for further development as anti-HCV agents.

  DOI：

  10.1021/jm049122i

文献信息

• [EN] INDOLE ACETAMIDES AS INHIBITORS OF THE HEPATITIS C VIRUS NS5B POLYMERASE<br/>[FR] ACETAMIDES D'INDOLE COMME INHIBITEURS DE LA POLYMERASE NS5B DU VIRUS DE L'HEPATITE C
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2004087714A1

  公开（公告）日：2004-10-14

  The present invention relates to indole and azaindole compounds of formula (I): wherein X1, X2, X3, X4, A1, Ar1, R1, R2 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。
• Antiviral indoles
  申请人：Stansfield Ian

  公开号：US20080153895A1

  公开（公告）日：2008-06-26

  Compounds of the formula (I): wherein A, B, D, M, Ar, W, X, Y, Z and R 1 are as defined herein, are useful in the prevention and treatment of hepatitis C infections. The compounds, their preparation, pharmaceutical compositions containing them and their use in medicine are disclosed.

  式（I）的化合物：其中A、B、D、M、Ar、W、X、Y、Z和R1如本文所定义，对预防和治疗丙型肝炎感染是有用的。这些化合物、它们的制备、含有它们的药物组合物以及它们在医学上的应用被披露。
• 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。
• Antiviral Indoles
  申请人：Stansfield Ian

  公开号：US20100076046A1

  公开（公告）日：2010-03-25

  Compounds of the formula (I) wherein A, B, D, M, Ar, W, X, Y, Z and R 1 are as defined herein, are useful in the prevention and treatment of hepatitis C infections. The compounds, their preparation, pharmaceutical compositions containing them and their use in medicine are disclosed.

  公式（I）中的化合物，其中A，B，D，M，Ar，W，X，Y，Z和R1的定义如下，对于预防和治疗丙型肝炎感染是有用的。本文公开了这些化合物的制备方法、含有它们的制药组合物以及它们在医学上的使用。
• Potent Inhibitors of Subgenomic Hepatitis C Virus RNA Replication through Optimization of Indole-<i>N</i>-Acetamide Allosteric Inhibitors of the Viral NS5B Polymerase
  作者：Steven Harper、Salvatore Avolio、Barbara Pacini、Marcello Di Filippo、Sergio Altamura、Licia Tomei、Giacomo Paonessa、Di Marco、Andrea Carfi、Claudio Giuliano、Julio Padron、Fabio Bonelli、Giovanni Migliaccio、Raffaele De Francesco、Ralph Laufer、Michael Rowley、Frank Narjes

  DOI：10.1021/jm050056+

  日期：2005.7.1

  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.