(2S,4R)-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinyl-cyclopropyl]-1-[(2S)-2-[(5-fluoro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)carbamoylamino]-3,3-dimethyl-butanoyl]-4-[[2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methyl-4-quinolyl]oxy]pyrrolidine-2-carboxamide | 1285533-23-4

• 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: (2S,4R)-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinyl-cyclopropyl]-1-[(2S)-2-[(5-fluoro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)carbamoylamino]-3,3-dimethyl-butanoyl]-4-[[2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methyl-4-quinolyl]oxy]pyrrolidine-2-carboxamide
• 英文别名: (2S,4R)-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-1-[(2S)-2-[(5-fluoro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)carbamoylamino]-3,3-dimethylbutanoyl]-4-[7-methoxy-8-methyl-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxypyrrolidine-2-carboxamide
• CAS: 1285533-23-4
• 化学式: C₄₅H₅₃BFN₇O₁₀S₂
• 分子量: 945.898
• InChiKey: VUPFPRBJOFORGO-SIVNUYGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.41
• 重原子数：
  66
• 可旋转键数：
  15
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  264
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  (4R)-1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-{[8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinyl]oxy}-L-proline 在 盐酸 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 NMM 、 二氯甲烷 、 水 为溶剂， 反应 28.0h， 生成 (2S,4R)-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinyl-cyclopropyl]-1-[(2S)-2-[(5-fluoro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)carbamoylamino]-3,3-dimethyl-butanoyl]-4-[[2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methyl-4-quinolyl]oxy]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Synthesis and SAR of acyclic HCV NS3 protease inhibitors with novel P4-benzoxaborole moieties

  摘要：

  We have synthesized and evaluated a new series of acyclic P4-benzoxaborole-based HCV NS3 protease inhibitors. Structure-activity relationships were investigated, leading to the identification of compounds 5g and 17 with low nanomolar potency in the enzymatic and cell-based replicon assay. The linker-truncated compound 5j was found to exhibit improved absorption and oral bioavailability in rats, suggesting that further reduction of molecular weight and polar surface area could result in improved drug-like properties of this novel series. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.006