(2R)-2-[[(2R)-2-[[(2S,4S)-1-[(2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoyl]-4-(phenylmethoxycarbonylamino)pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoic acid | 1400443-16-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R)-2-[[(2R)-2-[[(2S,4S)-1-[(2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoyl]-4-(phenylmethoxycarbonylamino)pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoic acid
• CAS: 1400443-16-4
• 化学式: C₄₈H₄₉N₅O₁₀
• 分子量: 855.945
• InChiKey: BPOQGBNUQKCGCI-BUMMRBMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  63
• 可旋转键数：
  20
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  213
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2R)-2-[[(2R)-2-[[(2S,4S)-1-[(2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoyl]-4-(phenylmethoxycarbonylamino)pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoic acid 在 N-甲基吗啉 、 氯甲酸异丁酯 、 ammonium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成
  参考文献：
  名称：

  cis-4-Amino-l-proline Residue As a Scaffold for the Synthesis of Cyclic and Linear Endomorphin-2 Analogues: Part 2

  摘要：

  Recently, we reported synthesis and activity of a constrained cyclic analogue of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) and related linear models containing the cis-4-amino-L-proline (cAmp) in place of native Pro(2). In the present article, the adopted rationale is the possible modulation of the receptor affinity of the cAmp containing EM-2 analogues by assigning a different stereochemistry to the Phe(3) and Phe(4) residues present in the ring. Thus, eight more analogues with different absolute configuration at the chiral center of the aromatic residues in positions 3 and 4 have been synthesized and their opioid activity examined. The stereochemical change at the alpha-carbon atoms leads to a meaningful enhancement of the affinity and activity toward mu opioid receptors with respect to the prototype compound 9: e.g., 9a, K-i(mu) = 63 nM, GPI (IC50) = 480 nM; 9b, K-i(mu) = 38 nM, GPI (IC50) = 330 nM.

  DOI：

  10.1021/jm300947s
• 作为产物：
  描述：

  在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 以100%的产率得到(2R)-2-[[(2R)-2-[[(2S,4S)-1-[(2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoyl]-4-(phenylmethoxycarbonylamino)pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoic acid
  参考文献：
  名称：

  cis-4-Amino-l-proline Residue As a Scaffold for the Synthesis of Cyclic and Linear Endomorphin-2 Analogues: Part 2

  摘要：

  Recently, we reported synthesis and activity of a constrained cyclic analogue of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) and related linear models containing the cis-4-amino-L-proline (cAmp) in place of native Pro(2). In the present article, the adopted rationale is the possible modulation of the receptor affinity of the cAmp containing EM-2 analogues by assigning a different stereochemistry to the Phe(3) and Phe(4) residues present in the ring. Thus, eight more analogues with different absolute configuration at the chiral center of the aromatic residues in positions 3 and 4 have been synthesized and their opioid activity examined. The stereochemical change at the alpha-carbon atoms leads to a meaningful enhancement of the affinity and activity toward mu opioid receptors with respect to the prototype compound 9: e.g., 9a, K-i(mu) = 63 nM, GPI (IC50) = 480 nM; 9b, K-i(mu) = 38 nM, GPI (IC50) = 330 nM.

  DOI：

  10.1021/jm300947s

文献信息

• <i>cis</i>-4-Amino-<scp>l</scp>-proline Residue As a Scaffold for the Synthesis of Cyclic and Linear Endomorphin-2 Analogues: Part 2
  作者：Adriano Mollica、Francesco Pinnen、Azzurra Stefanucci、Luisa Mannina、Anatoly P. Sobolev、Gino Lucente、Peg Davis、Josephine Lai、Shou-Wu Ma、Frank Porreca、Victor J. Hruby

  DOI：10.1021/jm300947s

  日期：2012.10.11

  Recently, we reported synthesis and activity of a constrained cyclic analogue of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) and related linear models containing the cis-4-amino-L-proline (cAmp) in place of native Pro(2). In the present article, the adopted rationale is the possible modulation of the receptor affinity of the cAmp containing EM-2 analogues by assigning a different stereochemistry to the Phe(3) and Phe(4) residues present in the ring. Thus, eight more analogues with different absolute configuration at the chiral center of the aromatic residues in positions 3 and 4 have been synthesized and their opioid activity examined. The stereochemical change at the alpha-carbon atoms leads to a meaningful enhancement of the affinity and activity toward mu opioid receptors with respect to the prototype compound 9: e.g., 9a, K-i(mu) = 63 nM, GPI (IC50) = 480 nM; 9b, K-i(mu) = 38 nM, GPI (IC50) = 330 nM.