(S)-[1-(2-methoxy-5-morpholin-4-ylphenyl)ethyl]carbamic acid tert-butyl ester | 701939-05-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (S)-[1-(2-methoxy-5-morpholin-4-ylphenyl)ethyl]carbamic acid tert-butyl ester
• CAS: 701939-05-1
• 化学式: C₁₈H₂₈N₂O₄
• 分子量: 336.431
• InChiKey: NCZYNGLRAHWBIS-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.12
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  60.03
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (S)-[1-(2-methoxy-5-morpholin-4-ylphenyl)ethyl]carbamic acid tert-butyl ester 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 生成 (E)-N-[(1S)-1-(2-methoxy-5-morpholin-4-ylphenyl)ethyl]-3-phenylprop-2-enamide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of Acrylamides as KCNQ2 Potassium Channel Openers

  摘要：

  A new class of acrylamides was synthesized, and the effects of these analogues on outward potassium current were evaluated by using two electrode voltage clamp recordings from Xenopus laevis oocytes expressing cloned mKCNQ2 channels. SAR studies indicated that the pharmacophore of the acrylamide series includes the (S) absolute configuration at the (1-phenyl)ethyl moiety and the alpha,beta-unsaturated acrylamide functionality with a free NH. This study identified (S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide ((S)-1) and (S)-N-[1-(4-fluoro-3morpholin-4-yl-phenyl)-ethyl]-3-(4-fluoro-phenyl)-acrylamide ((S)-2) as KCNQ2 openers for further electrophysiological evaluations. These two acrylamides demonstrated significant activity in the cortical spreading depression model of migraine as we reported previously.

  DOI：

  10.1021/jm0305826
• 作为产物：
  描述：

  (S)-1-(2-甲氧苯基)乙胺 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 N-溴代丁二酰亚胺(NBS) 、 三乙胺 、 2-(二叔丁基膦)联苯 、 sodium t-butanolate 作用下， 以 二氯甲烷 、 丙酮 、 甲苯 为溶剂， 反应 38.0h， 生成 (S)-[1-(2-methoxy-5-morpholin-4-ylphenyl)ethyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of Acrylamides as KCNQ2 Potassium Channel Openers

  摘要：

  A new class of acrylamides was synthesized, and the effects of these analogues on outward potassium current were evaluated by using two electrode voltage clamp recordings from Xenopus laevis oocytes expressing cloned mKCNQ2 channels. SAR studies indicated that the pharmacophore of the acrylamide series includes the (S) absolute configuration at the (1-phenyl)ethyl moiety and the alpha,beta-unsaturated acrylamide functionality with a free NH. This study identified (S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide ((S)-1) and (S)-N-[1-(4-fluoro-3morpholin-4-yl-phenyl)-ethyl]-3-(4-fluoro-phenyl)-acrylamide ((S)-2) as KCNQ2 openers for further electrophysiological evaluations. These two acrylamides demonstrated significant activity in the cortical spreading depression model of migraine as we reported previously.

  DOI：

  10.1021/jm0305826