(1R,2S)-1-{[trans-2-{(S)-1-[((S)-cyclohexyl(methoxycarbonyl)methyl)carbamoyl]-2,2-dimethylpropylcarbamoyl}-4-(7-methoxy-2-phenylquinolin-4-yloxy)cyclopent-2-enecarbonyl]amino}-2-vinylcyclopropanecarboxylic acid tert-butyl ester | 862174-50-3

• 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: (1R,2S)-1-{[trans-2-{(S)-1-[((S)-cyclohexyl(methoxycarbonyl)methyl)carbamoyl]-2,2-dimethylpropylcarbamoyl}-4-(7-methoxy-2-phenylquinolin-4-yloxy)cyclopent-2-enecarbonyl]amino}-2-vinylcyclopropanecarboxylic acid tert-butyl ester
• 英文别名: tert-butyl (1R,2S)-1-[[2-[[(1S)-1-[[(1S)-1-cyclohexyl-2-methoxy-2-oxo-ethyl]carbamoyl]-2,2-dimethyl-propyl]carbamoyl]-4-[(7-methoxy-2-phenyl-4-quinolyl)oxy]cyclopent-2-ene-1-carbonyl]amino]-2-vinyl-cyclopropanecarboxylate；tert-butyl (1R,2S)-1-[[2-[[(2S)-1-[[(1S)-1-cyclohexyl-2-methoxy-2-oxoethyl]amino]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-4-(7-methoxy-2-phenylquinolin-4-yl)oxycyclopent-2-ene-1-carbonyl]amino]-2-ethenylcyclopropane-1-carboxylate
• CAS: 862174-50-3
• 化学式: C₄₈H₆₀N₄O₉
• 分子量: 837.026
• InChiKey: DQNQZXSKAFOLDH-ZXOLFWBWSA-N

物化性质

• 沸点：
  953.1±65.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  61
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  171
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (1R,2S)-1-{[trans-2-{(S)-1-[((S)-cyclohexyl(methoxycarbonyl)methyl)carbamoyl]-2,2-dimethylpropylcarbamoyl}-4-(7-methoxy-2-phenylquinolin-4-yloxy)cyclopent-2-enecarbonyl]amino}-2-vinylcyclopropanecarboxylic acid tert-butyl ester 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以49%的产率得到(1R,2S)-1-{[(1R,4R)-2-{(S)-1-[((S)-cyclohexyl-methoxycarbonyl-methyl)-carbamoyl]-2,2-dimethyl-propylcarbamoyl}-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopent-2-enecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid
  参考文献：
  名称：

  Synthesis of novel potent hepatitis C virus NS3 protease inhibitors: Discovery of 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a N-acyl-l-hydroxyproline bioisostere

  摘要：

  Potent tetrapeptidic inhibitors of the HCV NS3 protease have been developed incorporating 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a new N-acyl-L-hydroxyproline mimic. The hydroxycyclopentene template was synthesized in eight steps from commercially available, (syn)-tetrahydrophthalic anhydride. Three different amino acids were explored in the PI-position and in the P2-position the hydroxyl group of the cyclopentene template was substituted with 7-methoxy-2-phenyl-quinolin-4-ol. The P3/P4-positions were then optimized from a set of six amino acid derivatives. All inhibitors were evaluated in an in vitro assay using the full-length NS3 protease. Several potent inhibitors were identified, the most promising exhibiting a K-i value of 1.1 nM. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.044
• 作为产物：
  描述：

  N-Boc-L-叔亮氨酸 在 三乙基硅烷 、 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-) 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (1R,2S)-1-{[trans-2-{(S)-1-[((S)-cyclohexyl(methoxycarbonyl)methyl)carbamoyl]-2,2-dimethylpropylcarbamoyl}-4-(7-methoxy-2-phenylquinolin-4-yloxy)cyclopent-2-enecarbonyl]amino}-2-vinylcyclopropanecarboxylic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis of novel potent hepatitis C virus NS3 protease inhibitors: Discovery of 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a N-acyl-l-hydroxyproline bioisostere

  摘要：

  Potent tetrapeptidic inhibitors of the HCV NS3 protease have been developed incorporating 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a new N-acyl-L-hydroxyproline mimic. The hydroxycyclopentene template was synthesized in eight steps from commercially available, (syn)-tetrahydrophthalic anhydride. Three different amino acids were explored in the PI-position and in the P2-position the hydroxyl group of the cyclopentene template was substituted with 7-methoxy-2-phenyl-quinolin-4-ol. The P3/P4-positions were then optimized from a set of six amino acid derivatives. All inhibitors were evaluated in an in vitro assay using the full-length NS3 protease. Several potent inhibitors were identified, the most promising exhibiting a K-i value of 1.1 nM. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.044

文献信息

• Hcv Ns-3 Serine Protease Inhibitors
  申请人：Rosenquist Asa

  公开号：US20070203072A1

  公开（公告）日：2007-08-30

  Peptidomimetic compounds are described which inhibit the NS3 protease of the hepatitis C virus (HCV). The compounds have the formula where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

  本文描述了一种抑制丙型肝炎病毒（HCV）的NS3蛋白酶的肽类类似物化合物。该化合物的化学式中，变量定义如规范中所提供。该化合物包括一个碳环P2单元，与抑制剂更远离天然底物的名义剪切位点的那些部分的新型连接结合，该连接将远侧的肽键方向相对于靠近剪切位点的肽键反转。
• HCV NS-3 SERINE PROTEASE INHIBITORS
  申请人：Rosenquist Asa

  公开号：US20100166706A1

  公开（公告）日：2010-07-01

  Methods drawn to peptidomimetic compounds which inhibit the NS3 protease of the hepatitis C virus (HCV), are described. The compounds have the formula (VI) where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

  本文描述了用于抑制丙型肝炎病毒（HCV）NS3蛋白酶的肽类类似物化合物的方法。这些化合物的公式为（VI），其中变量定义如规范所述。这些化合物包括一个碳环P2单元，与抑制剂更远离原生底物的部分具有新颖的连接，该连接将远离切割位点的肽键的方向与靠近切割位点的肽键的方向相反。
• HCV NS-3 serine protease inhibitors
  申请人：Medivir AB

  公开号：US10172846B2

  公开（公告）日：2019-01-08

  Methods drawn to peptidomimetic compounds which inhibit the NS3 protease of the hepatitis C virus (HCV), are described. The compounds have the formula (VI) where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

  本文介绍了抑制丙型肝炎病毒（HCV）NS3蛋白酶的拟肽化合物的制备方法。这些化合物具有式 (VI)，其中变量定义如说明书所提供。这些化合物包括一个碳环 P2 单元，该单元与抑制剂中离原生底物名义裂解位点较远的部分有一种新的连接，这种连接使远端肽键的方向与裂解位点近端的肽键方向相反。
• US7671032B2
  申请人：——

  公开号：US7671032B2

  公开（公告）日：2010-03-02
• [EN] HCV NS-3 SERINE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE LA NS-3 SERINE PROTEASE DU VHC
  申请人：MEDIVIR AB

  公开号：WO2005073195A2

  公开（公告）日：2005-08-11

  Peptidomimetic compounds are described which inhibit the NS3 protease of the hepatitis C virus (HCV). The compounds have the formula where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.