methyl (4R)-1-[(2S)-2-cyclopentyl-2-(hept-6-en-1-ylamino)acetyl]-4-[(7-ethenylisoquinolin-1-yl)oxy]-L-prolinate | 1179843-45-8

• 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-cyclopentyl-2-(hept-6-en-1-ylamino)acetyl]-4-[(7-ethenylisoquinolin-1-yl)oxy]-L-prolinate
• 英文别名: methyl (2S,4R)-1-[(2S)-2-cyclopentyl-2-(hept-6-enylamino)acetyl]-4-(7-ethenylisoquinolin-1-yl)oxypyrrolidine-2-carboxylate
• CAS: 1179843-45-8
• 化学式: C₃₁H₄₁N₃O₄
• 分子量: 519.684
• InChiKey: LQTOQYOCFWYOKF-PKXQUSJVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (4R)-1-[(2S)-2-cyclopentyl-2-(hept-6-en-1-ylamino)acetyl]-4-[(7-ethenylisoquinolin-1-yl)oxy]-L-prolinate 、 三氟乙酸 在 詹氏钌催化剂-1 作用下， 以 二氯甲烷 为溶剂， 生成 (2R,4S,7S,14E)-7-cyclopentyl-4-(methoxycarbonyl)-6-oxo-3,4,6,7,8,9,10,11,12,13-decahydro-2H-16,18-etheno-2,5-methanopyrido[3,2-r][1,5,8]oxadiazacyclononadecin-8-ium trifluoroacetate
  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
• 作为产物：
  描述：

  methyl (2S,4R)-4-(7-ethenylisoquinolin-1-yl)oxypyrrolidine-2-carboxylate 、 (2S)-cyclopentyl(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82%的产率得到methyl (4R)-1-[(2S)-2-cyclopentyl-2-(hept-6-en-1-ylamino)acetyl]-4-[(7-ethenylisoquinolin-1-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

• 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
  作者：Steven Harper、Marco Ferrara、Benedetta Crescenzi、Marco Pompei、Maria Cecilia Palumbi、Jillian M. DiMuzio、Monica Donghi、Fabrizio Fiore、Uwe Koch、Nigel J. Liverton、Silvia Pesci、Alessia Petrocchi、Michael Rowley、Vincenzo Summa、Cristina Gardelli

  DOI：10.1021/jm900372w

  日期：2009.8.13

  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.