2-[(S)-amino-(4-fluorophenyl)methyl]prop-2-enoic acid | 1385032-63-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-[(S)-amino-(4-fluorophenyl)methyl]prop-2-enoic acid
• CAS: 1385032-63-2
• 化学式: C₁₀H₁₀FNO₂
• 分子量: 195.193
• InChiKey: CKXKSYRFEVBYCX-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  tert-butyl ((1S)-2-(dimethoxyphosphoryl)-1-(4-fluorophenyl)-3-oxo-3-(1H-pyrrol-1-yl)propyl)carbamate 在 盐酸 、 甲醇 、 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 22.5h， 生成 2-[(S)-amino-(4-fluorophenyl)methyl]prop-2-enoic acid
  参考文献：
  名称：

  A New Class of Highly Potent and Selective Endomorphin-1 Analogues Containing α-Methylene-β-aminopropanoic Acids (Map)

  摘要：

  A new class of endomorphin-1 (EM-1) analogues were synthesized by introduction of novel unnatural alpha-methylene-beta-amino acids (Map) at position 3 or/and position 4. Their binding and functional activity, metabolic stability, and antinociceptive activity were determined and compared. Most of these analogues showed high affinities for the mu-opioid receptor and an increased stability in mouse brain homogenates compared with EM-1. Examination of cAMP accumulation and ERK1/2 phosphorylation in HEK293 cells confirmed the agonist properties of these analogues. Among these new analogues, H-Tyr-Pro-Trp-(2-furyl)Map-NH2 (analogue 12) exhibited the highest binding potency (K-i(mu) = 0.221 nM) and efficacy (EC50 = 0.0334 nM, E-max = 97.14%). This analogue also displayed enhanced antinociceptive activity in vivo in comparison to EM-1. Molecular modeling approaches were then carried out to demonstrate the interaction pattern of these analogues with the opioid receptors. We found that, compared to EM-1, the incorporation of our synthesized Map at position 4 would bring the analogue to a closer binding mode with the mu-opioid receptor.

  DOI：

  10.1021/jm300664y