trans-5-[((S)-1-tert-butoxycarbonylbutyl)carbamoyl]-3-(7-methoxy-2-phenylquinolin-4-yloxy)cyclopent-1-enecarboxylic acid lithium salt

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: trans-5-[((S)-1-tert-butoxycarbonylbutyl)carbamoyl]-3-(7-methoxy-2-phenylquinolin-4-yloxy)cyclopent-1-enecarboxylic acid lithium salt
• 英文别名: lithium;3-(7-methoxy-2-phenylquinolin-4-yl)oxy-5-[[(2S)-1-[(2-methylpropan-2-yl)oxy]-1-oxopentan-2-yl]carbamoyl]cyclopentene-1-carboxylate
• 化学式: C₃₂H₃₅N₂O₇*Li
• 分子量: 566.58
• InChiKey: QGFLINNZLVLKRE-RKEXWMRTSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.98
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  trans-5-[((S)-1-tert-butoxycarbonylbutyl)carbamoyl]-3-(7-methoxy-2-phenylquinolin-4-yloxy)cyclopent-1-enecarboxylic acid lithium salt 、 (2-amino-3-methyl-butyrylamino)-cyclohexyl acetic acid methyl ester 在 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 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 2.5h， 以13%的产率得到(S)-2-{[(1R,4R)-{(S)-1-[((S)-cyclohexyl(methoxycarbonyl)methyl)carbamoyl]-2-methylpropylcarbamoyl}-4-(7-methoxy-2-phenylquinolin-4-yloxy)cyclopent-1-enecarbonyl]amino}pentanoic acid tert-butyl ester
  参考文献：
  名称：

  [EN] HCV NS-3 SERINE PROTEASE INHIBITORS
  [FR] INHIBITEURS DE LA NS-3 SERINE PROTEASE DU VHC

  摘要：

  公开号：

  WO2005073195A3
• 作为产物：
  描述：

  Z-L-正缬氨酸 在 palladium on activated charcoal 4-二甲氨基吡啶 、 lithium hydroxide 、 偶氮二甲酸二异丙酯 、 氢气 、 N,N-二异丙基乙胺 、 三苯基膦 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 11.0h， 生成 trans-5-[((S)-1-tert-butoxycarbonylbutyl)carbamoyl]-3-(7-methoxy-2-phenylquinolin-4-yloxy)cyclopent-1-enecarboxylic acid lithium salt
  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.
• [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：WO2005073195A3

  公开（公告）日：2005-09-29