2-cyano-4-ethylhex-2-enoic acid benzyl ester | 852206-60-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-cyano-4-ethylhex-2-enoic acid benzyl ester
• 英文别名: 2-Cyano-4-ethyl-hex-2-enoic acid benzyl ester；benzyl (E)-2-cyano-4-ethylhex-2-enoate
• CAS: 852206-60-1
• 化学式: C₁₆H₁₉NO₂
• 分子量: 257.332
• InChiKey: NHZJFBXWJIJLAE-XNTDXEJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  2-cyano-4-ethylhex-2-enoic acid benzyl ester 在 platinum(IV) oxide 、 palladium on activated charcoal 盐酸 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 60.0 ℃ 、330.95 kPa 条件下， 反应 35.0h， 生成 1-aminomethyl-2-(1-ethylpropyl)cyclopropanecarboxylic acid
  参考文献：
  名称：

  Novel Cyclopropyl β-Amino Acid Analogues of Pregabalin and Gabapentin That Target the α₂-δ Protein

  摘要：

  As part of a program aimed at generating compounds with affinity for the alpha(2)-delta subunit of voltage-gated calcium channels, several novel beta-amino acids were prepared using an efficient nitroalkane-mediated cyclopropanation as a key step. Depending on the ester that was chosen, the target amino acids could be prepared in as few as three steps. The cyclopropyl amino acids derived from ketones proved to be potent binders of the alpha 2-beta subunit of voltage-gated calcium channels, but did not interact with the large neutral amino acid system L (leucine) transporter. Anticonvulsant effects were observed in vivo with compound 34 but only after intracerebroventricular (icv) administration, presumably due to inadequate brain concentrations of the drug being achieved following oral dosing. However, pregabalin 1 was active in the DBA/2 model after oral (and icv) dosing, supporting a hypothesis that active transport is a prerequisite for such zwitterionic species to cross the blood-brain barrier.

  DOI：

  10.1021/jm0491086
• 作为产物：
  描述：

  2-乙基丁醛 、 氰基乙酸苄酯 在 哌啶 、 溶剂黄146 作用下， 反应 1.67h， 以95%的产率得到2-cyano-4-ethylhex-2-enoic acid benzyl ester
  参考文献：
  名称：

  Novel Cyclopropyl β-Amino Acid Analogues of Pregabalin and Gabapentin That Target the α₂-δ Protein

  摘要：

  As part of a program aimed at generating compounds with affinity for the alpha(2)-delta subunit of voltage-gated calcium channels, several novel beta-amino acids were prepared using an efficient nitroalkane-mediated cyclopropanation as a key step. Depending on the ester that was chosen, the target amino acids could be prepared in as few as three steps. The cyclopropyl amino acids derived from ketones proved to be potent binders of the alpha 2-beta subunit of voltage-gated calcium channels, but did not interact with the large neutral amino acid system L (leucine) transporter. Anticonvulsant effects were observed in vivo with compound 34 but only after intracerebroventricular (icv) administration, presumably due to inadequate brain concentrations of the drug being achieved following oral dosing. However, pregabalin 1 was active in the DBA/2 model after oral (and icv) dosing, supporting a hypothesis that active transport is a prerequisite for such zwitterionic species to cross the blood-brain barrier.

  DOI：

  10.1021/jm0491086

文献信息

• Cyclopropyl beta-amino acid derivatives
  申请人：——

  公开号：US20040147608A1

  公开（公告）日：2004-07-29

  This invention relates to novel cyclopropyl &bgr;-amino acids derivatives of the formula 1 wherein R 1 through R 4 are defined as in the specification, pharmaceutical compositions containing them and their use for the treatment of various central nervous system and other disorders. The cyclopropyl &bgr;-amino acids derivatives of this invention exhibit activity as alpha2delta ligands (&agr;2&dgr; ligands). Such compounds have affinity for the &agr;2&dgr; subunit of a calcium channel.

  这项发明涉及公式1的新型环丙基β-氨基酸衍生物，其中R1至R4如规范中定义，含有它们的药物组合物以及它们用于治疗各种中枢神经系统和其他疾病的用途。本发明的环丙基β-氨基酸衍生物表现出作为α2δ配体（α2δ配体）的活性。这类化合物对钙通道的α2δ亚基具有亲和力。
• CYCLOPROPYL BETA-AMINO ACID DERIVATIVES
  申请人：Warner-Lambert Company LLC

  公开号：EP1592661A2

  公开（公告）日：2005-11-09
• US7030267B2
  申请人：——

  公开号：US7030267B2

  公开（公告）日：2006-04-18
• [EN] CYCLOPROPYL BETA-AMINO ACID DERIVATIVES<br/>[FR] DERIVES D'ACIDES BETA-AMINES DE CYCLOPROPYLE
  申请人：WARNER LAMBERT CO

  公开号：WO2004065361A2

  公开（公告）日：2004-08-05

  This invention relates to novel cyclopropyl β-amino acids derivatives of the formula (I) wherein R1 through R4 are defined as in the specification, pharmaceutical compositions containing them and their use for the treatment of various central nervous system and other disorders. The cyclopropyl β-amino acids derivatives of this invention exhibit activity as alpha2delta ligands (α2δ ligands). Such compounds have affinity for the α2δ subunit of a calcium channel.
• Novel Cyclopropyl β-Amino Acid Analogues of Pregabalin and Gabapentin That Target the α₂-δ Protein
  作者：Jacob B. Schwarz、Sian E. Gibbons、Shelley R. Graham、Norman L. Colbry、Peter R. Guzzo、Van-Duc Le、Mark G. Vartanian、Jack J. Kinsora、Susan M. Lotarski、Zheng Li、Melvin R. Dickerson、Ti-Zhi Su、Mark L. Weber、Ayman El-Kattan、Andrew J. Thorpe、Sean D. Donevan、Charles P. Taylor、David J. Wustrow

  DOI：10.1021/jm0491086

  日期：2005.4.1

  As part of a program aimed at generating compounds with affinity for the alpha(2)-delta subunit of voltage-gated calcium channels, several novel beta-amino acids were prepared using an efficient nitroalkane-mediated cyclopropanation as a key step. Depending on the ester that was chosen, the target amino acids could be prepared in as few as three steps. The cyclopropyl amino acids derived from ketones proved to be potent binders of the alpha 2-beta subunit of voltage-gated calcium channels, but did not interact with the large neutral amino acid system L (leucine) transporter. Anticonvulsant effects were observed in vivo with compound 34 but only after intracerebroventricular (icv) administration, presumably due to inadequate brain concentrations of the drug being achieved following oral dosing. However, pregabalin 1 was active in the DBA/2 model after oral (and icv) dosing, supporting a hypothesis that active transport is a prerequisite for such zwitterionic species to cross the blood-brain barrier.