(1R,2S)-1-{[trans-2-{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 | 959346-16-8

• 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-{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-(methylamino)-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-(methylamino)-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: 959346-16-8
• 化学式: C₄₈H₆₁N₅O₈
• 分子量: 836.041
• InChiKey: KTMOMEXVMIMBDM-ZXOLFWBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  61
• 可旋转键数：
  17
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  174
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (1R,2S)-1-{[trans-2-{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48%的产率得到(1R,2S)-1-[[(1R,4R)-2-[[(1S)-1-[[(1S)-1-cyclohexyl-2-(methylamino)-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-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 、 lithium hydroxide 、 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 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 (1R,2S)-1-{[trans-2-{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

• 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
  作者：Fredrik Thorstensson、Fredrik Wångsell、Ingemar Kvarnström、Lotta Vrang、Elizabeth Hamelink、Katarina Jansson、Anders Hallberg、Åsa Rosenquist、Bertil Samuelsson

  DOI：10.1016/j.bmc.2006.10.044

  日期：2007.1

  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.