19-trimethyl-5,6,9,10-tetrahydro-2H,8H-14,18:17,20-di(metheno)-1,7,11,4,10,12,19-benzodioxathiatetraazacyclodocosine-3,13(4H,12h,19H)-dione 11,11-dioxide | 1208129-89-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: 19-trimethyl-5,6,9,10-tetrahydro-2H,8H-14,18:17,20-di(metheno)-1,7,11,4,10,12,19-benzodioxathiatetraazacyclodocosine-3,13(4H,12h,19H)-dione 11,11-dioxide
• 英文别名: 28-Cyclohexyl-7-methoxy-2,13,19-trimethyl-20,20-dioxo-10,16-dioxa-20lambda6-thia-2,13,19,21-tetrazatetracyclo[21.3.1.13,26.04,9]octacosa-1(26),3(28),4(9),5,7,23(27),24-heptaene-12,22-dione；28-cyclohexyl-7-methoxy-2,13,19-trimethyl-20,20-dioxo-10,16-dioxa-20λ6-thia-2,13,19,21-tetrazatetracyclo[21.3.1.13,26.04,9]octacosa-1(26),3(28),4(9),5,7,23(27),24-heptaene-12,22-dione
• CAS: 1208129-89-8
• 化学式: C₃₁H₄₀N₄O₇S
• 分子量: 612.747
• InChiKey: UIKWSRUDYYZYQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  43
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-溴-3-环己基-1H-吲哚-6-羧酸甲酯 在 四(三苯基膦)钯 、 sulfonamide 、 水 、 sodium hydride 、 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 potassium hydroxide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 12.75h， 生成 19-trimethyl-5,6,9,10-tetrahydro-2H,8H-14,18:17,20-di(metheno)-1,7,11,4,10,12,19-benzodioxathiatetraazacyclodocosine-3,13(4H,12h,19H)-dione 11,11-dioxide
  参考文献：
  名称：

  Finger-loop inhibitors of the HCV NS5b polymerase. Part 1: Discovery and optimization of novel 1,6- and 2,6-macrocyclic indole series

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2012.03.097

文献信息

• [EN] MACROCYCLIC INDOLE DERIVATIVES USEFUL AS HEPATITIS C VIRUS INHIBITORS<br/>[FR] DÉRIVÉS D'INDOLE MACROCYCLIQUES UTILES COMME INHIBITEURS DU VIRUS DE L'HÉPATITE C
  申请人：TIBOTEC PHARM LTD

  公开号：WO2010018233A1

  公开（公告）日：2010-02-18

  Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein Y, R1, R2, R4 and n have the meaning defined in the claims. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in HCV therapy.

  公式（I）的HCV复制抑制剂包括立体化学异构形式，以及它们的盐、水合物、溶剂合物，其中Y、R1、R2、R4和n的含义如权利要求中所定义。本发明还涉及制备所述化合物的方法，含有它们的药物组合物以及它们在HCV治疗中的应用。
• MACROCYCLIC INDOLE DERIVATIVES USEFUL AS HEPATITIS C VIRUS INHIBITORS
  申请人：MC GOWAN David Craig

  公开号：US20110152279A1

  公开（公告）日：2011-06-23

  Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein Y, R 1 , R 2 , R 4 and n have the meaning defined in the claims. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in HCV therapy.

  公式（I）的HCV复制抑制剂，包括立体化学异构体形式、盐、水合物、溶剂化物，其中Y、R1、R2、R4和n的含义如权利要求所定义。本发明还涉及制备上述化合物的方法、含有它们的药物组合物和它们在HCV治疗中的应用。
• US8357687B2
  申请人：——

  公开号：US8357687B2

  公开（公告）日：2013-01-22
• 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.