ethyl (3S)-3-cyano-4-trimethylsilylbutanoate | 1403674-31-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl (3S)-3-cyano-4-trimethylsilylbutanoate
• CAS: 1403674-31-6
• 化学式: C₁₀H₁₉NO₂Si
• 分子量: 213.352
• InChiKey: RTDYHXKJBUQOGI-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.42
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (3S)-3-cyano-4-trimethylsilylbutanoate 在 氢气 作用下， 以 甲醇 、 水 为溶剂， 25.0 ℃ 、450.01 kPa 条件下， 反应 48.0h， 生成 (S)-4-amino-3-(trimethylsilyl)methylbutanoic acid
  参考文献：
  名称：

  Silicon-Containing GABA Derivatives, Silagaba Compounds, as Orally Effective Agents for Treating Neuropathic Pain without Central-Nervous-System-Related Side Effects

  摘要：

  Neuropathic pain is a chronic condition resulting from neuronal damage. Pregabalin, the (S)-isomer of 3-isobutyl-gamma-aminobutyric acid (GABA), is widely used to treat neuropathic pain, despite the occurrence of central nervous system (CNS)-related side effects such as dizziness and somnolence. Here we describe the pharmacology of novel GABA derivatives containing silicon-carbon bonds, silagaba compounds. Silagaba131, 132, and 161 showed pregabalin-like analgesic activities in animal models of neuropathic pain, but in contrast to pregabalin they did not impair neuromuscular coordination in rotarod tests. Pharmacokinetic studies showed that brain exposure to silagaba compounds was lower than that to pregabalin. Surprisingly, despite their potent analgesic action in vivo, silagaba compounds showed only weak binding to alpha 2-delta protein. These compounds may be useful to study mechanisms of neuropathic pain. Our results also indicate that silagaba132 and 161 are candidates for orally effective treatment of neuropathic pain without CNS-related side effects.

  DOI：

  10.1021/cn500053d
• 作为产物：
  描述：

  diethyl 2-cyano-2-(trimethylsilylmethyl)succinate 在 lithium bromide 作用下， 以 aq. phosphate buffer 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl (3S)-3-cyano-4-trimethylsilylbutanoate
  参考文献：
  名称：

  (R)- and (S)-4-Amino-3-(trimethylsilyl)methylbutanoic acids ameliorate neuropathic pain without central nervous system-related side effects

  摘要：

  Neuropathic pain is a chronic pain condition resulting from neuronal damage, and is usually treated with pregabalin or gabapentin, which are structurally related to gamma-aminobutyric acid (GABA) and are originally developed as anticonvulsant drugs. Here, we report the synthesis and pharmacology of (R)- and (S)-4-amino-3-(trimethylsilyl)methylbutanoic acids (1a and 1b), which showed analgesic activity as potent as that of pregabalin in the Chung spinal nerve ligation model. However, unlike pregabalin, 1a and 1b do not have antiepileptic effects, and they are therefore promising candidates for selective therapeutic agents to treat neuropathic pain without central nervous system-related side effects. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.10.001

文献信息

• (R)- and (S)-4-Amino-3-(trimethylsilyl)methylbutanoic acids ameliorate neuropathic pain without central nervous system-related side effects
  作者：Hideaki Muratake、Ai Ito、Takahiro Toda、Hideyuki Suzuki、Hiroshi Fukasawa、Makoto Tsuda、Kazuhide Inoue、Kiyoshi Sugiyama、Koichi Shudo

  DOI：10.1016/j.bmcl.2012.10.001

  日期：2012.12

  Neuropathic pain is a chronic pain condition resulting from neuronal damage, and is usually treated with pregabalin or gabapentin, which are structurally related to gamma-aminobutyric acid (GABA) and are originally developed as anticonvulsant drugs. Here, we report the synthesis and pharmacology of (R)- and (S)-4-amino-3-(trimethylsilyl)methylbutanoic acids (1a and 1b), which showed analgesic activity as potent as that of pregabalin in the Chung spinal nerve ligation model. However, unlike pregabalin, 1a and 1b do not have antiepileptic effects, and they are therefore promising candidates for selective therapeutic agents to treat neuropathic pain without central nervous system-related side effects. (C) 2012 Published by Elsevier Ltd.
• Silicon-Containing GABA Derivatives, Silagaba Compounds, as Orally Effective Agents for Treating Neuropathic Pain without Central-Nervous-System-Related Side Effects
  作者：Hiroshi Fukasawa、Hideaki Muratake、Ai Ito、Hideyuki Suzuki、Yohei Amano、Marina Nagae、Kiyoshi Sugiyama、Koichi Shudo

  DOI：10.1021/cn500053d

  日期：2014.7.16

  Neuropathic pain is a chronic condition resulting from neuronal damage. Pregabalin, the (S)-isomer of 3-isobutyl-gamma-aminobutyric acid (GABA), is widely used to treat neuropathic pain, despite the occurrence of central nervous system (CNS)-related side effects such as dizziness and somnolence. Here we describe the pharmacology of novel GABA derivatives containing silicon-carbon bonds, silagaba compounds. Silagaba131, 132, and 161 showed pregabalin-like analgesic activities in animal models of neuropathic pain, but in contrast to pregabalin they did not impair neuromuscular coordination in rotarod tests. Pharmacokinetic studies showed that brain exposure to silagaba compounds was lower than that to pregabalin. Surprisingly, despite their potent analgesic action in vivo, silagaba compounds showed only weak binding to alpha 2-delta protein. These compounds may be useful to study mechanisms of neuropathic pain. Our results also indicate that silagaba132 and 161 are candidates for orally effective treatment of neuropathic pain without CNS-related side effects.