methyl (5R,7S,10S,17E)-3,9-dioxo-10-(propan-2-yl)-6,7,9,10,11,12,13,14,15,16-decahydro-1H,5H-2,22:5,8-dimethano-4,2,8,11-benzoxatriazacycloicosine-7(3H)-carboxylate trifluoroacetate | 1000063-54-6

• 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 (5R,7S,10S,17E)-3,9-dioxo-10-(propan-2-yl)-6,7,9,10,11,12,13,14,15,16-decahydro-1H,5H-2,22:5,8-dimethano-4,2,8,11-benzoxatriazacycloicosine-7(3H)-carboxylate trifluoroacetate
• 英文别名: methyl (1R,12E,20S,23S)-3,21-dioxo-20-propan-2-yl-2-oxa-4,19,22-triazatetracyclo[20.2.1.14,7.06,11]hexacosa-6,8,10,12-tetraene-23-carboxylate;2,2,2-trifluoroacetic acid
• CAS: 1000063-54-6
• 化学式: C₂HF₃O₂*C₂₇H₃₇N₃O₅
• 分子量: 597.632
• InChiKey: HFRAMYJEESKFDH-RPHQTDRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.12
• 重原子数：
  42
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  methyl (5R,7S,10S,17E)-3,9-dioxo-10-(propan-2-yl)-6,7,9,10,11,12,13,14,15,16-decahydro-1H,5H-2,22:5,8-dimethano-4,2,8,11-benzoxatriazacycloicosine-7(3H)-carboxylate trifluoroacetate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成 methyl (1R,20S,23S)-3,21-dioxo-20-propan-2-yl-2-oxa-4,22-diaza-19-azoniatetracyclo[20.2.1.14,7.06,11]hexacosa-6(11),7,9-triene-23-carboxylate;2,2,2-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 N-(hept-6-en-1-yl)-L-valyl-(4R)-4-{[(4-ethenyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}-L-prolinate 、 三氟乙酸 在 詹氏钌催化剂-1 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 以78%的产率得到methyl (5R,7S,10S,17E)-3,9-dioxo-10-(propan-2-yl)-6,7,9,10,11,12,13,14,15,16-decahydro-1H,5H-2,22:5,8-dimethano-4,2,8,11-benzoxatriazacycloicosine-7(3H)-carboxylate 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

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.