(2S,4R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-4-fluoropyrrolidine-2-carboxylic acid hydrochloride | 1192649-54-9

• 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)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-4-fluoropyrrolidine-2-carboxylic acid hydrochloride
• 英文别名: (2S,4R)-1-[4,4-bis(3-methylthiophen-2-yl)but-3-enyl]-4-fluoropyrrolidine-2-carboxylic acid;hydrochloride
• CAS: 1192649-54-9
• 化学式: C₁₉H₂₂FNO₂S₂*ClH
• 分子量: 415.981
• InChiKey: BVUFOBIIBOGNAF-XMZRARIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.17
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  97
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 (2S,4R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-4-fluoropyrrolidine-2-carboxylic acid hydrochloride 在 sodium hydroxide 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 以67%的产率得到(2S,4R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-2-diazoacetyl-4-fluoropyrrolidine
  参考文献：
  名称：

  Synthesis and biological evaluation of 4-fluoroproline and 4-fluoropyrrolidine-2-acetic acid derivatives as new GABA uptake inhibitors

  摘要：

  Preparation for the N-alkylated derivatives of enantiomerically pure (2S)-4-fluoroproline and (2S)-4-fluoropyrrolidine-2-acetic acid is described. The final compounds were evaluated as potential GAT-1 uptake inhibitors via cultured cell lines expressing mouse GAT-1. Compared with their corresponding 4-hydroxy compounds, these derivatives exhibited slight improvement on their inhibitory potency, but still much weaker than their corresponding compounds with no substituents at the C-4 of the pyrrolidine moiety, with the most potent affinity being about 1/15 fold as that of Tiagabine. The drastic decrease of their affinity may arise from sharp reduction of their basicity due to strong inductive effect of the 4-fluorine. However the configuration of the C-4 linking fluorine did not have much influence on their affinity for GAT-1. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.010
• 作为产物：
  描述：

  methyl (2S,4R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-4-fluoropyrrolidine-2-carboxylate 在 乙醇 、 sodium hydroxide 、 盐酸 、 水 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以92%的产率得到(2S,4R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-4-fluoropyrrolidine-2-carboxylic acid hydrochloride
  参考文献：
  名称：

  Synthesis and biological evaluation of 4-fluoroproline and 4-fluoropyrrolidine-2-acetic acid derivatives as new GABA uptake inhibitors

  摘要：

  Preparation for the N-alkylated derivatives of enantiomerically pure (2S)-4-fluoroproline and (2S)-4-fluoropyrrolidine-2-acetic acid is described. The final compounds were evaluated as potential GAT-1 uptake inhibitors via cultured cell lines expressing mouse GAT-1. Compared with their corresponding 4-hydroxy compounds, these derivatives exhibited slight improvement on their inhibitory potency, but still much weaker than their corresponding compounds with no substituents at the C-4 of the pyrrolidine moiety, with the most potent affinity being about 1/15 fold as that of Tiagabine. The drastic decrease of their affinity may arise from sharp reduction of their basicity due to strong inductive effect of the 4-fluorine. However the configuration of the C-4 linking fluorine did not have much influence on their affinity for GAT-1. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.010

文献信息

• Synthesis and biological evaluation of 4-fluoroproline and 4-fluoropyrrolidine-2-acetic acid derivatives as new GABA uptake inhibitors
  作者：Weiping Zhuang、Xueqing Zhao、Gang Zhao、Lihe Guo、Yunyang Lian、Jingming Zhou、Dongsheng Fang

  DOI：10.1016/j.bmc.2009.08.010

  日期：2009.9

  Preparation for the N-alkylated derivatives of enantiomerically pure (2S)-4-fluoroproline and (2S)-4-fluoropyrrolidine-2-acetic acid is described. The final compounds were evaluated as potential GAT-1 uptake inhibitors via cultured cell lines expressing mouse GAT-1. Compared with their corresponding 4-hydroxy compounds, these derivatives exhibited slight improvement on their inhibitory potency, but still much weaker than their corresponding compounds with no substituents at the C-4 of the pyrrolidine moiety, with the most potent affinity being about 1/15 fold as that of Tiagabine. The drastic decrease of their affinity may arise from sharp reduction of their basicity due to strong inductive effect of the 4-fluorine. However the configuration of the C-4 linking fluorine did not have much influence on their affinity for GAT-1. (C) 2009 Elsevier Ltd. All rights reserved.