[(4R,6S,14S,18R)-14-amino-4-(cyclopropylsulfonylcarbamoyl)-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-en-18-yl] 4-fluoro-1,3-dihydroisoindole-2-carboxylate

• 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: [(4R,6S,14S,18R)-14-amino-4-(cyclopropylsulfonylcarbamoyl)-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-en-18-yl] 4-fluoro-1,3-dihydroisoindole-2-carboxylate
• 化学式: C₃₀H₃₈FN₅O₇S
• 分子量: 631.725
• InChiKey: XIHKRRKIQPJCPN-HKYAXPHXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  44
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  177
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-羟基-1,3-二氢苯并[c][1,2]氧杂硼杂环烷-6-羧酸 、 [(4R,6S,14S,18R)-14-amino-4-(cyclopropylsulfonylcarbamoyl)-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-en-18-yl] 4-fluoro-1,3-dihydroisoindole-2-carboxylate 在 HATU 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以50%的产率得到C₃₈H₄₃BFN₅O₁₀S
  参考文献：
  名称：

  Synthesis and biological evaluations of P4-benzoxaborole-substituted macrocyclic inhibitors of HCV NS3 protease

  摘要：

  We disclose here a series of P4-benzoxaborole-substituted macrocyclic HCV protease inhibitors. These inhibitors are potent against HCV NS3 protease, their anti-HCV replicon potencies are largely impacted by substitutions on benzoxaborole ring system and P2* groups. P2* 2-thiazole-isoquinoline provides best replicon potency. The in vitro SAR studies and in vivo PK evaluations of selected compounds are described herein. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.071
• 作为产物：
  描述：

  danoprevir 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以83%的产率得到[(4R,6S,14S,18R)-14-amino-4-(cyclopropylsulfonylcarbamoyl)-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-en-18-yl] 4-fluoro-1,3-dihydroisoindole-2-carboxylate
  参考文献：
  名称：

  Synthesis and biological evaluations of P4-benzoxaborole-substituted macrocyclic inhibitors of HCV NS3 protease

  摘要：

  We disclose here a series of P4-benzoxaborole-substituted macrocyclic HCV protease inhibitors. These inhibitors are potent against HCV NS3 protease, their anti-HCV replicon potencies are largely impacted by substitutions on benzoxaborole ring system and P2* groups. P2* 2-thiazole-isoquinoline provides best replicon potency. The in vitro SAR studies and in vivo PK evaluations of selected compounds are described herein. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.071

文献信息

• Synthesis and biological evaluations of P4-benzoxaborole-substituted macrocyclic inhibitors of HCV NS3 protease
  作者：Charles Z. Ding、Yong-Kang Zhang、Xianfeng Li、Yang Liu、Suoming Zhang、Yasheen Zhou、Jacob J. Plattner、Stephen J. Baker、Liang Liu、Maosheng Duan、Richard L. Jarvest、Jingjing Ji、Wieslaw M. Kazmierski、Matthew D. Tallant、Lois L. Wright、Gary K. Smith、Renae M. Crosby、Amy A. Wang、Zhi-Jie Ni、Wuxin Zou、Jon Wright

  DOI：10.1016/j.bmcl.2010.10.071

  日期：2010.12

  We disclose here a series of P4-benzoxaborole-substituted macrocyclic HCV protease inhibitors. These inhibitors are potent against HCV NS3 protease, their anti-HCV replicon potencies are largely impacted by substitutions on benzoxaborole ring system and P2* groups. P2* 2-thiazole-isoquinoline provides best replicon potency. The in vitro SAR studies and in vivo PK evaluations of selected compounds are described herein. (C) 2010 Elsevier Ltd. All rights reserved.