(5R,7S,10S,12S)-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-12-methyl-3,9-dioxo-10-(propan-2-yl)-6,7,9,10,11,12,13,14,15,16,17,18-dodecahydro-1H,5H-2,22:5,8-dimethano-4,2,8,11-benzoxatriazacycloicosine-7(3H)-carboxamide | 1179843-26-5

• 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: (5R,7S,10S,12S)-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-12-methyl-3,9-dioxo-10-(propan-2-yl)-6,7,9,10,11,12,13,14,15,16,17,18-dodecahydro-1H,5H-2,22:5,8-dimethano-4,2,8,11-benzoxatriazacycloicosine-7(3H)-carboxamide
• 英文别名: (5R,7S,10R,12S)-N-{(1R,2S)-1-[(Cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-12-methyl-3,9-dioxo-10-(propan-2-yl)-6,7,9,10,11,12,13,14,15,16,17,18-dodecahydro-1H,5H-2,22:5,8-dimethano-4,2,8,11-benzoxatriazacycloicosine-7(3H)-carboxamide；(1R,18S,20S,23S)-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-18-methyl-3,21-dioxo-20-propan-2-yl-2-oxa-4,19,22-triazatetracyclo[20.2.1.14,7.06,11]hexacosa-6(11),7,9-triene-23-carboxamide
• CAS: 1179843-26-5
• 化学式: C₃₆H₅₁N₅O₇S
• 分子量: 697.896
• InChiKey: HPGNQBRQZSIBDI-UNKXUBGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  49
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  163
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (5R,7S,10S,12S)-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-12-methyl-3,9-dioxo-10-(propan-2-yl)-6,7,9,10,11,12,13,14,15,16,17,18-dodecahydro-1H,5H-2,22:5,8-dimethano-4,2,8,11-benzoxatriazacycloicosine-7(3H)-carboxamide 、 三氟乙酸 以 水 、 乙腈 为溶剂， 生成 (5R,7S,10S,12S)-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-12-methyl-3,9-dioxo-10-(propan-2-yl)-6,7,9,10,11,12,13,14,15,16,17,18-dodecahydro-1H,5H-2,22:5,8-dimethano-4,2,8,11-benzoxatriazacycloicosine-7(3H)-carboxamide trifloroacetate
  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：

  (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide 、 在 4-二甲氨基吡啶 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 14.08h， 生成 (5R,7S,10S,12S)-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-12-methyl-3,9-dioxo-10-(propan-2-yl)-6,7,9,10,11,12,13,14,15,16,17,18-dodecahydro-1H,5H-2,22:5,8-dimethano-4,2,8,11-benzoxatriazacycloicosine-7(3H)-carboxamide
  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