methyl (2S,4R)-4-(6-ethenyl-7-methoxy-2-phenylquinolin-4-yl)oxypyrrolidine-2-carboxylate | 957752-60-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl (2S,4R)-4-(6-ethenyl-7-methoxy-2-phenylquinolin-4-yl)oxypyrrolidine-2-carboxylate
• CAS: 957752-60-2
• 化学式: C₂₄H₂₄N₂O₄
• 分子量: 404.466
• InChiKey: BXKUDAJSBFKHNT-UTKZUKDTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (2S,4R)-4-(6-ethenyl-7-methoxy-2-phenylquinolin-4-yl)oxypyrrolidine-2-carboxylate 、 (2S)-cyclohexyl(hept-6-en-1-ylamino)ethanoic acid 在 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-) 作用下， 以 二氯甲烷 为溶剂， 以35%的产率得到methyl (4R)-1-[(2S)-2-cyclohexyl-2-(hept-6-en-1-ylamino)acetyl]-4-[(7-methoxy-2-phenyl-6-vinylquinolin-4-yl)oxy]-L-prolinate
  参考文献：
  名称：

  Inhibitors of the Hepatitis C Virus NS3 Protease with Basic Amine Functionality at the P3-Amino Acid N-Terminus: Discovery and Optimization of a New Series of P2−P4 Macrocycles

  摘要：

  In a follow-Lip to our recent disclosure of P2-P4 macrocyclic inhibitors of the hepatitis C virus (HCV) NS3 protease (e.g., 1, Chart 1), we report a new but related compound series featuring a basic amine at the N-terminus of the P3-amino acid residue. Replacement of the electroneutral P3-amino acid capping group (which is a feature of almost all tripeptide-like inhibitors of NS3 reported to date) with a basic group is not only tolerated but can result in advantageous cell based potency. Optimization of this new class of P3-amine based inhibitors gave compounds such as 25 and 26 that combine excellent cell based activity with pharmacokinetic properties that are attractive for an antiviral targeting HCV.

  DOI：

  10.1021/jm900372w

文献信息

• Macrocyclic Compounds as Antiviral Agents
  申请人：Crescenzi Benedetta

  公开号：US20090312241A1

  公开（公告）日：2009-12-17

  The present invention relates to macrocyclic compounds of formula (I): wherein W, n, m, R 1 , R 2 , R 3 , R 4 , R 5 , R a , M, Z and ring B 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.

  本发明涉及式（I）的大环化合物：其中W、n、m、R1、R2、R3、R4、R5、Ra、M、Z和环B在此处定义，并其药用盐，包含它们的药物组合物，以及它们用于治疗或预防丙型肝炎病毒感染的用途。
• Novel P2–P4 macrocyclic inhibitors of HCV NS3/4A protease by P3 succinamide fragment depeptidization strategy
  作者：Marco Pompei、Maria Emilia Di Francesco、Silvia Pesci、Uwe Koch、Sue Ellen Vignetti、Maria Veneziano、Paola Pace、Vincenzo Summa

  DOI：10.1016/j.bmcl.2009.11.005

  日期：2010.1

  have disclosed a novel class of P2–P4 macrocyclic inhibitors of NS3/4A protease containing a carbamate functionality as capping group at the P3 N-terminus. Herein we report our work aimed at further depeptidizing the P3 region by replacement of the urethane function with a succinamide motif. This peptidomimetic approach has led to the discovery of novel P2–P4 macrocyclic inhibitors of HCV NS3/4A protease

  丙型肝炎代表着严重的全球卫生保健问题。最近，我们公开了一类新的NS3 / 4A蛋白酶的P2-P4大环抑制剂，其在P3 N端含有一个氨基甲酸酯官能团作为封端基团。本文中，我们报告了我们的工作，旨在通过用琥珀酰胺基序取代氨基甲酸酯功能来进一步使P3区去肽化。这种拟肽方法已导致发现具有亚纳摩尔酶亲和力的HCV NS3 / 4A蛋白酶的新型P2-P4大环抑制剂。除了是有效的HCV亚基因组复制抑制剂外，该系列中的优化类似物还具有诱人的PK特性，并在口服后在大鼠中显示出令人鼓舞的肝脏水平。
• HCV NS3 Protease Inhibitors
  申请人：Liverton Nigel J

  公开号：US20100286185A1

  公开（公告）日：2010-11-11

  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.

  本发明涉及式(I)的大环化合物，它们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。
• THERAPEUTIC COMPOUNDS
  申请人：McCauley John A.

  公开号：US20110002884A1

  公开（公告）日：2011-01-06

  A class of macrocyclic compounds of formula (I), wherein R 1 , R 3 , R 4 , R a , R b , A, B, Z, M, W and n are defined herein, that are useful as inhibitors of viral proteases, particularly the hepatitis C virus (HCV) NS3 protease, are provided. Also provided are processes for the synthesis and use of such macrocyclic compounds for treating or preventing HCV infection.

  提供一类具有化学式（I）的大环化合物，其中R1、R3、R4、Ra、Rb、A、B、Z、M、W和n在此定义，这些化合物可用作病毒蛋白酶抑制剂，特别是乙型肝炎病毒（HCV）NS3蛋白酶的抑制剂。还提供了合成和使用这种大环化合物用于治疗或预防HCV感染的过程。
• US8314062B2
  申请人：——

  公开号：US8314062B2

  公开（公告）日：2012-11-20