methyl (S)-2-(benzo[d][1,3]dioxol-5-yl((tert-butoxycarbonyl)amino)methyl)acrylate | 1346684-14-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: methyl (S)-2-(benzo[d][1,3]dioxol-5-yl((tert-butoxycarbonyl)amino)methyl)acrylate
• CAS: 1346684-14-7
• 化学式: C₁₇H₂₁NO₆
• 分子量: 335.357
• InChiKey: ACSGTZYCEMQCBD-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.71
• 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：
  0.41
• 拓扑面积：
  83.09
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl (S)-2-(benzo[d][1,3]dioxol-5-yl((tert-butoxycarbonyl)amino)methyl)acrylate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以80%的产率得到(S)-2-(benzo[d][1,3]dioxol-5-yl((tert-butoxycarbonyl)amino)methyl)acrylic 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
• 作为产物：
  描述：

  聚合甲醛 、 tert-butyl ((1S)-1-(benzo[d][1,3]dioxol-5-yl)-2-(dimethoxyphosphoryl)-3-oxo-3-(1H-pyrrol-1-yl)propyl)carbamate 、 sodium methylate 在 甲醇 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 8.5h， 生成 methyl (S)-2-(benzo[d][1,3]dioxol-5-yl((tert-butoxycarbonyl)amino)methyl)acrylate
  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