methyl (4R)-1-{(2S)-2-[({[(1R,2S)-2-allylcyclopentyl]oxy}carbonyl)amino]-2-cyclopentylacetyl}-4-[(2-ethoxy-7-methoxy-6-vinylquinolin-4-yl)oxy]-L-prolinate | 1021438-27-6

• 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: methyl (4R)-1-{(2S)-2-[({[(1R,2S)-2-allylcyclopentyl]oxy}carbonyl)amino]-2-cyclopentylacetyl}-4-[(2-ethoxy-7-methoxy-6-vinylquinolin-4-yl)oxy]-L-prolinate
• 英文别名: methyl (2S,4R)-1-[(2S)-2-cyclopentyl-2-[[(1R,2S)-2-prop-2-enylcyclopentyl]oxycarbonylamino]acetyl]-4-(6-ethenyl-2-ethoxy-7-methoxyquinolin-4-yl)oxypyrrolidine-2-carboxylate
• CAS: 1021438-27-6
• 化学式: C₃₆H₄₇N₃O₈
• 分子量: 649.784
• InChiKey: ZITXTFHFBBIMTD-QSMDVGKPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  47
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl (4R)-1-{(2S)-2-[({[(1R,2S)-2-allylcyclopentyl]oxy}carbonyl)amino]-2-cyclopentylacetyl}-4-[(2-ethoxy-7-methoxy-6-vinylquinolin-4-yl)oxy]-L-prolinate 在 lithium hydroxide monohydrate 、 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 、 甲醇 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 (3R,5S,8S,12R,16S,18E)-8-cyclopentyl-N-((1R,2S)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-vinylcyclopropyl)-25-ethoxy-21-methoxy-7,10-dioxo-2,11-dioxa-6,9,24-triazapentacyclo[18.6.2.13,6.012,16.023,27]nonacosa-1(27),18,20,22,23,25,27-heptaene-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
• 作为产物：
  描述：

  (1R,2S)-2-(2-propenyl)cyclopentyl acetate 在 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 potassium carbonate 、 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 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 9.0h， 生成 methyl (4R)-1-{(2S)-2-[({[(1R,2S)-2-allylcyclopentyl]oxy}carbonyl)amino]-2-cyclopentylacetyl}-4-[(2-ethoxy-7-methoxy-6-vinylquinolin-4-yl)oxy]-L-prolinate
  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

• HCV NS3 PROTEASE INHIBITORS
  申请人：Liverton Nigel J.

  公开号：US20100093779A1

  公开（公告）日：2010-04-15

  The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

  本发明涉及一种公式（I）的大环化合物，其可用作丙型肝炎病毒（HCV）NS3蛋白酶的抑制剂，其合成以及其用于治疗或预防HCV感染的用途。
• WO2008/51514
  申请人：——

  公开号：——

  公开（公告）日：——
• US8309540B2
  申请人：——

  公开号：US8309540B2

  公开（公告）日：2012-11-13
• 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.