methyl 2-bromo-3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-1H-indole-6-carboxylate | 735287-01-1

• 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-bromo-3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-1H-indole-6-carboxylate
• 英文别名: 2-bromo-3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-1H-indole-6-carboxylate；methyl 2-bromo-3-cyclohexyl-1-dimethylcarbamoylmethyl-1H-indole-6-carboxylate；methyl 2-bromo-3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]indole-6-carboxylate
• CAS: 735287-01-1
• 化学式: C₂₀H₂₅BrN₂O₃
• 分子量: 421.334
• InChiKey: JCCVHFRUGAFMMU-UHFFFAOYSA-N

物化性质

• 沸点：
  542.1±50.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  51.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-bromo-3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-1H-indole-6-carboxylate 在 氢氧化钾 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 乙醇 为溶剂， 反应 30.0h， 生成 3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(3-furyl)-1H-indole-6-carboxylic acid
  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：

  吲哚-6-甲酸甲酯 在 palladium dihydroxide N-溴代丁二酰亚胺(NBS) 、 氢气 、 sodium methylate 、 sodium hydride 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 生成 methyl 2-bromo-3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-1H-indole-6-carboxylate
  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] VIRAL POLYMERASE INHIBITORS<br/>[FR] INHIBITEURS DE POLYMERASE VIRALE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2004065367A1

  公开（公告）日：2004-08-05

  An isomer, enantiomer, diastereoisomer or tautomer of a compound, represented by formula (I): wherein wherein A, B, R2, R3, L, M1, M2, M3, M4, Y1, Y0, Z and Sp are as defined in claim 1, or a salt thereof, as an inhibitor of HCV NS5B polymerase.

  化合物的异构体、对映体、非对映异构体或互变异构体，由式(I)所代表：其中A、B、R2、R3、L、M1、M2、M3、M4、Y1、Y0、Z和Sp如权利要求1中定义，或其盐，作为HCV NS5B聚合酶的抑制剂。
• [EN] INDOLE DERIVATIVES AS ANTIVIRAL AGENTS<br/>[FR] DERIVES D'INDOLE EN TANT QU'AGENTS ANTIVIRAUX
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2006029912A1

  公开（公告）日：2006-03-23

  The present invention relates to indole compounds of the formula (I): wherein R1, R2, R3, R4, A, E and X 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)的吲哚化合物，其中R1、R2、R3、R4、A、E和X如本文所定义，并其药学上可接受的盐，用于预防和治疗丙型肝炎感染。
• [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。
• Viral polymerase inhibitors
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20040171626A1

  公开（公告）日：2004-09-02

  An isomer, enantiomer, diastereoisomer or tautomer of a compound, represented by formula I: 1 wherein wherein A, B, R 2 , R 3 , L, M 1 , M 2 , M 3 , M 4 , Y 1 , Y 0 , Z and Sp are as defined in claim 1, or a salt thereof, as an inhibitor of HCV NS5B polymerase.

  化合物的同分异构体、对映异构体、顺反异构体或互变异构体，由式I：1所表示，其中A、B、R2、R3、L、M1、M2、M3、M4、Y1、Y0、Z和Sp如权利要求1所定义，或其盐，作为HCV NS5B聚合酶的抑制剂。
• Pentacyclic Indole Derivatives as Antiviral Agents
  申请人：Capito Elena

  公开号：US20100009959A1

  公开（公告）日：2010-01-14

  The present invention relates to pentacyclic indole derivatives of formula (I): wherein A, Ar, R 1 , R 2 , W, X, Y and Z are defined herein, and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising them, and their use for the treatment or prevention of infection by hepatitis C virus.

  本发明涉及公式（I）的五环吲哚衍生物：其中A，Ar，R1，R2，W，X，Y和Z在此定义，并且其药学上可接受的盐，包括它们的制药组合物，以及它们用于治疗或预防丙型肝炎病毒感染的用途。