methyl (4R)-2,3,4,5-tetrahydro-1H-2-benzazepine-4-carboxylate | 1448639-72-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: methyl (4R)-2,3,4,5-tetrahydro-1H-2-benzazepine-4-carboxylate
• CAS: 1448639-72-2
• 化学式: C₁₂H₁₅NO₂
• 分子量: 205.257
• InChiKey: HLNPWFMVYUHRKU-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (4R)-2,3,4,5-tetrahydro-1H-2-benzazepine-4-carboxylate 、 (S)-3-(Boc-氨基)-4-苯基丁酸 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.75h， 生成 (R)-methyl 2-((S)-3-(tert-butoxycarbonylamino)-4-phenylbutanoyl)-2,3,4,5-tetrahydro-1Hbenzo[c]azepine-4-carboxylate
  参考文献：
  名称：

  Structural and Biological Exploration of Phe³–Phe⁴-Modified Endomorphin-2 Peptidomimetics

  摘要：

  This study reports on our ongoing investigation on hybrid EM-2 analogues, in which the great potential of beta-amino acids was exploited to generate multiple conformational modifications at the key positions 3 and 4 of the parent peptide. The effect on the opioid binding affinity was evaluated, by means of ligand stimulated binding assays, which indicated a high nanomolar affinity toward the mu-receptor, with appreciable mu/delta selectivity, for some of the new compounds. The three-dimensional properties of the high affinity mu opioid receptor (MOR) ligands were investigated by proton nuclear magnetic resonance, molecular dynamics, and docking studies. In solution, the structures showed extended conformations, which are in agreement with the commonly accepted pharmacophore model for EM-2. From docking studies on an active form of the MOR model, different ligand-receptor interactions have been identified, thus confirming the ability of active compounds to assume a biologically active conformation.

  DOI：

  10.1021/ml400189r
• 作为产物：
  描述：

  在 聚合甲醛 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 methyl (4R)-2,3,4,5-tetrahydro-1H-2-benzazepine-4-carboxylate
  参考文献：
  名称：

  Structural and Biological Exploration of Phe³–Phe⁴-Modified Endomorphin-2 Peptidomimetics

  摘要：

  This study reports on our ongoing investigation on hybrid EM-2 analogues, in which the great potential of beta-amino acids was exploited to generate multiple conformational modifications at the key positions 3 and 4 of the parent peptide. The effect on the opioid binding affinity was evaluated, by means of ligand stimulated binding assays, which indicated a high nanomolar affinity toward the mu-receptor, with appreciable mu/delta selectivity, for some of the new compounds. The three-dimensional properties of the high affinity mu opioid receptor (MOR) ligands were investigated by proton nuclear magnetic resonance, molecular dynamics, and docking studies. In solution, the structures showed extended conformations, which are in agreement with the commonly accepted pharmacophore model for EM-2. From docking studies on an active form of the MOR model, different ligand-receptor interactions have been identified, thus confirming the ability of active compounds to assume a biologically active conformation.

  DOI：

  10.1021/ml400189r
• 作为试剂：
  描述：

  (S)-3-(Boc-氨基)-4-苯基丁酸 、 methyl (S)-2-(1,2,3,4-tetrahydroisoquinolin-3-yl)acetate 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 、 methyl (4R)-2,3,4,5-tetrahydro-1H-2-benzazepine-4-carboxylate 作用下， 以 二氯甲烷 为溶剂， 反应 0.75h， 生成 methyl 2-((S)-2-((S)-3-(tert-butoxycarbonylamino)-4-phenylbutanoyl)-1,2,3,4-tetrahydroisoquinolin-3-yl) acetate
  参考文献：
  名称：

  Structural and Biological Exploration of Phe³–Phe⁴-Modified Endomorphin-2 Peptidomimetics

  摘要：

  This study reports on our ongoing investigation on hybrid EM-2 analogues, in which the great potential of beta-amino acids was exploited to generate multiple conformational modifications at the key positions 3 and 4 of the parent peptide. The effect on the opioid binding affinity was evaluated, by means of ligand stimulated binding assays, which indicated a high nanomolar affinity toward the mu-receptor, with appreciable mu/delta selectivity, for some of the new compounds. The three-dimensional properties of the high affinity mu opioid receptor (MOR) ligands were investigated by proton nuclear magnetic resonance, molecular dynamics, and docking studies. In solution, the structures showed extended conformations, which are in agreement with the commonly accepted pharmacophore model for EM-2. From docking studies on an active form of the MOR model, different ligand-receptor interactions have been identified, thus confirming the ability of active compounds to assume a biologically active conformation.

  DOI：

  10.1021/ml400189r