P-[1-[[[(5R,7S,10S)-10-(1,1-Dimethylethyl)-6,7,9,10,11,12,14,15,16,17,18,19-dodecahydro-15,15-dimethyl-3,9,12-trioxo-3H,5H-2,23:5,8-dimethano-1H-4,13,2,8,11-benzodioxatriazacycloheneicosin-7-yl]carbonyl]amino]-2-ethenylcyclopropyl]phosphonic acid | 1161182-29-1

• 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: P-[1-[[[(5R,7S,10S)-10-(1,1-Dimethylethyl)-6,7,9,10,11,12,14,15,16,17,18,19-dodecahydro-15,15-dimethyl-3,9,12-trioxo-3H,5H-2,23:5,8-dimethano-1H-4,13,2,8,11-benzodioxatriazacycloheneicosin-7-yl]carbonyl]amino]-2-ethenylcyclopropyl]phosphonic acid
• 英文别名: [1-[[(1R,21S,24S)-21-tert-butyl-16,16-dimethyl-3,19,22-trioxo-2,18-dioxa-4,20,23-triazatetracyclo[21.2.1.14,7.06,11]heptacosa-6(11),7,9-triene-24-carbonyl]amino]-2-ethenylcyclopropyl]phosphonic acid
• CAS: 1161182-29-1
• 化学式: C₃₄H₄₉N₄O₉P
• 分子量: 688.758
• InChiKey: SUMHIZFFMCZBCB-RJOXJRTASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  48
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  175
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (1R,21S,24S)-21-tert-butyl-N-(1-diethoxyphosphoryl-2-ethenylcyclopropyl)-16,16-dimethyl-3,19,22-trioxo-2,18-dioxa-4,20,23-triazatetracyclo[21.2.1.14,7.06,11]heptacosa-6(11),7,9-triene-24-carboxamide 在 碘代三甲硅烷 作用下， 以 乙腈 为溶剂， 以15%的产率得到P-[1-[[[(5R,7S,10S)-10-(1,1-Dimethylethyl)-6,7,9,10,11,12,14,15,16,17,18,19-dodecahydro-15,15-dimethyl-3,9,12-trioxo-3H,5H-2,23:5,8-dimethano-1H-4,13,2,8,11-benzodioxatriazacycloheneicosin-7-yl]carbonyl]amino]-2-ethenylcyclopropyl]phosphonic acid
  参考文献：
  名称：

  Phosphorous acid analogs of novel P2–P4 macrocycles as inhibitors of HCV–NS3 protease

  摘要：

  HCV-NS3 protease is essential for viral replication and NS3 protease inhibitors have shown proof of concept in clinical trials. Novel P2-P4 macrocycle inhibitors of NS3/4A comprising a P1 C-terminal carboxylic acid have recently been disclosed. A series of analogs, in which the carboxylic residue is replaced by phosphorous acid functionalities were synthesized and found to be inhibitors of the NS3 protease. Among them the methylphosphinate analogue showed nanomolar level of enzyme inhibition and sub-micromolar potency in the replication assay. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.038

文献信息

• Phosphorous acid analogs of novel P2–P4 macrocycles as inhibitors of HCV–NS3 protease
  作者：Marco Pompei、Maria Emilia Di Francesco、Uwe Koch、Nigel J. Liverton、Vincenzo Summa

  DOI：10.1016/j.bmcl.2009.03.038

  日期：2009.5

  HCV-NS3 protease is essential for viral replication and NS3 protease inhibitors have shown proof of concept in clinical trials. Novel P2-P4 macrocycle inhibitors of NS3/4A comprising a P1 C-terminal carboxylic acid have recently been disclosed. A series of analogs, in which the carboxylic residue is replaced by phosphorous acid functionalities were synthesized and found to be inhibitors of the NS3 protease. Among them the methylphosphinate analogue showed nanomolar level of enzyme inhibition and sub-micromolar potency in the replication assay. (C) 2009 Elsevier Ltd. All rights reserved.