(3R,5S,8S,12R,17S)-8-cyclohexyl-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-26-ethoxy-22-methoxy-7,10-dioxo-2,11-dioxa-6,9,25-triazapentacyclo[19.6.2.13,6.012,17.024,28]triaconta-1(27),19,21(29),22,24(28),25-hexaene-5-carboxamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3R,5S,8S,12R,17S)-8-cyclohexyl-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-26-ethoxy-22-methoxy-7,10-dioxo-2,11-dioxa-6,9,25-triazapentacyclo[19.6.2.13,6.012,17.024,28]triaconta-1(27),19,21(29),22,24(28),25-hexaene-5-carboxamide
• 化学式: C₄₄H₅₇N₅O₁₀S
• 分子量: 848.03
• InChiKey: DMHDFSSOXNVSGH-LROUOUKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  60
• 可旋转键数：
  10
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  200
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  4-溴-3-甲氧基苯胺 在 盐酸 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 lithium hydroxide monohydrate 、 caesium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 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 、 N-甲基吡咯烷酮 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.25h， 生成 (3R,5S,8S,12R,17S)-8-cyclohexyl-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-26-ethoxy-22-methoxy-7,10-dioxo-2,11-dioxa-6,9,25-triazapentacyclo[19.6.2.13,6.012,17.024,28]triaconta-1(27),19,21(29),22,24(28),25-hexaene-5-carboxamide
  参考文献：
  名称：

  Development of macrocyclic inhibitors of HCV NS3/4A protease with cyclic constrained P2–P4 linkers

  摘要：

  A series of macrocyclic compounds containing a cyclic constraint in the P2-P4 linker region have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155 K, A156T, A156 V, and D168 V mutant activity while maintaining high rat liver exposure. The effect of the constraint is most dramatic against gt 1b A156 mutants where similar to 20-fold improvements in potency are achieved by introduction of a variety of ring systems into the P2-P4 linker. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.061

文献信息

• Development of macrocyclic inhibitors of HCV NS3/4A protease with cyclic constrained P2–P4 linkers
  作者：Michael T. Rudd、Charles J. McIntyre、Joseph J. Romano、John W. Butcher、M. Katharine Holloway、Kimberly Bush、Kevin T. Nguyen、Kevin F. Gilbert、Terry A. Lyle、Nigel J. Liverton、Bang-Lin Wan、Vincenzo Summa、Steven Harper、Michael Rowley、Joseph P. Vacca、Steven S. Carroll、Christine Burlein、Jillian M. DiMuzio、Adam Gates、Donald J. Graham、Qian Huang、Steven W. Ludmerer、Stephanie McClain、Carolyn McHale、Mark Stahlhut、Christine Fandozzi、Anne Taylor、Nicole Trainor、David B. Olsen、John A. McCauley

  DOI：10.1016/j.bmcl.2012.09.061

  日期：2012.12

  A series of macrocyclic compounds containing a cyclic constraint in the P2-P4 linker region have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155 K, A156T, A156 V, and D168 V mutant activity while maintaining high rat liver exposure. The effect of the constraint is most dramatic against gt 1b A156 mutants where similar to 20-fold improvements in potency are achieved by introduction of a variety of ring systems into the P2-P4 linker. (C) 2012 Elsevier Ltd. All rights reserved.