methyl (4R)-4-((2-ethoxy-7-methoxy-6-vinylquinolin-4-yl)oxy)-L-prolinate hydrochloride | 1025369-53-2

• 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)-4-((2-ethoxy-7-methoxy-6-vinylquinolin-4-yl)oxy)-L-prolinate hydrochloride
• 英文别名: methyl (2S,4R)-4-(6-ethenyl-2-ethoxy-7-methoxyquinolin-4-yl)oxypyrrolidine-2-carboxylate;hydrochloride
• CAS: 1025369-53-2
• 化学式: C₂₀H₂₄N₂O₅*ClH
• 分子量: 408.882
• InChiKey: XLEBPMPREVFUEL-CACIRBSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.99
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (4R)-4-((2-ethoxy-7-methoxy-6-vinylquinolin-4-yl)oxy)-L-prolinate hydrochloride 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 21.0h， 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：

  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 、 caesium carbonate 、 三乙胺 作用下， 以 N-甲基吡咯烷酮 、 乙醇 、 二氯甲烷 为溶剂， 反应 25.25h， 生成 methyl (4R)-4-((2-ethoxy-7-methoxy-6-vinylquinolin-4-yl)oxy)-L-prolinate hydrochloride
  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

• THERAPEUTIC COMPOUNDS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2268285B1

  公开（公告）日：2018-06-27
• WO2008/51514
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.