(5R,7S,10S)-10-tert-Butyl-N-[(1R,2S)-2-ethenyl-1-{[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-4-yl)sulfonyl]carbamoyl}cyclopropyl]-15,15-dimethyl-3,9,12-trioxo-6,7,9,10,11,12,14,15,16,17,18,19-dodecahydro-1H,5H-2,23:5,8-dimethano-4,13,2,8,11-benzodioxatriazacyclohenicosine-7(3H)-carboxamide | 1261295-18-4

• 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)-10-tert-Butyl-N-[(1R,2S)-2-ethenyl-1-{[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-4-yl)sulfonyl]carbamoyl}cyclopropyl]-15,15-dimethyl-3,9,12-trioxo-6,7,9,10,11,12,14,15,16,17,18,19-dodecahydro-1H,5H-2,23:5,8-dimethano-4,13,2,8,11-benzodioxatriazacyclohenicosine-7(3H)-carboxamide
• 英文别名: (1R,21S,24S)-21-tert-butyl-N-[(1R,2S)-2-ethenyl-1-[(1-hydroxy-3H-2,1-benzoxaborol-4-yl)sulfonylcarbamoyl]cyclopropyl]-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
• CAS: 1261295-18-4
• 化学式: C₄₂H₅₄BN₅O₁₁S
• 分子量: 847.795
• InChiKey: MHBXBSZECPHEFS-KMVUKFFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.79
• 重原子数：
  60
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  218
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-sulfamoyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 在 盐酸 、 4-二甲氨基吡啶 、 异丁基硼酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 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 甲醇 、 正己烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (5R,7S,10S)-10-tert-Butyl-N-[(1R,2S)-2-ethenyl-1-{[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-4-yl)sulfonyl]carbamoyl}cyclopropyl]-15,15-dimethyl-3,9,12-trioxo-6,7,9,10,11,12,14,15,16,17,18,19-dodecahydro-1H,5H-2,23:5,8-dimethano-4,13,2,8,11-benzodioxatriazacyclohenicosine-7(3H)-carboxamide
  参考文献：
  名称：

  Synthesis of new acylsulfamoyl benzoxaboroles as potent inhibitors of HCV NS3 protease

  摘要：

  HCV NS3/4A serine protease is essential for the replication of the HCV virus and has been a clinically validated target. A series of HCV NS3/4A protease inhibitors containing a novel acylsulfamoyl benzoxaborole moiety at the P1 ' region was synthesized and evaluated. The resulting P1-P3 and P2-P4 macrocyclic inhibitors exhibited sub-nanomolar potency in the enzymatic assay and low nanomolar activity in the cell-based replicon assay. The in vivo PK evaluations of selected compounds are also described. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.007

文献信息

• Synthesis of new acylsulfamoyl benzoxaboroles as potent inhibitors of HCV NS3 protease
  作者：Xianfeng Li、Yong-Kang Zhang、Yang Liu、Suoming Zhang、Charles Z. Ding、Yasheen Zhou、Jacob J. Plattner、Stephen J. Baker、Liang Liu、Wei Bu、Wieslaw M. Kazmierski、Lois L. Wright、Gary K. Smith、Richard L. Jarvest、Maosheng Duan、Jing-Jing Ji、Joel P. Cooper、Matthew D. Tallant、Renae M. Crosby、Katrina Creech、Zhi-Jie Ni、Wuxin Zou、Jon Wright

  DOI：10.1016/j.bmcl.2010.10.007

  日期：2010.12

  HCV NS3/4A serine protease is essential for the replication of the HCV virus and has been a clinically validated target. A series of HCV NS3/4A protease inhibitors containing a novel acylsulfamoyl benzoxaborole moiety at the P1 ' region was synthesized and evaluated. The resulting P1-P3 and P2-P4 macrocyclic inhibitors exhibited sub-nanomolar potency in the enzymatic assay and low nanomolar activity in the cell-based replicon assay. The in vivo PK evaluations of selected compounds are also described. (C) 2010 Elsevier Ltd. All rights reserved.