[((S)-2-{(R)-2-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-4-methanesulfinyl-butyrylamino}-3-phenyl-propionyl)-methyl-amino]-acetic acid; compound with trifluoro-acetic acid | 108269-72-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: [((S)-2-{(R)-2-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-4-methanesulfinyl-butyrylamino}-3-phenyl-propionyl)-methyl-amino]-acetic acid; compound with trifluoro-acetic acid
• 英文别名: 2-[[(2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylsulfinylbutanoyl]amino]-3-phenylpropanoyl]-methylamino]acetic acid;2,2,2-trifluoroacetic acid
• CAS: 108269-72-3
• 化学式: C₂HF₃O₂*C₂₆H₃₄N₄O₇S
• 分子量: 660.669
• InChiKey: LLNABJSFEBDYQM-PVSZZWRSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.42
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  236
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  Boc-Tyr-D-Met-Phe-OH 在 sodium hydroxide 、 双氧水 、 1-羟基苯并三唑 、 苯甲醚 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.67h， 生成 [((S)-2-{(R)-2-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-4-methanesulfinyl-butyrylamino}-3-phenyl-propionyl)-methyl-amino]-acetic acid; compound with trifluoro-acetic acid
  参考文献：
  名称：

  Synthesis and activity profiles of new dermorphin-(1-4) peptide analogs

  摘要：

  A new series of 12 dermorphin tetrapeptides, W-Tyr-D-MetO-Phe-Xaa-Y (W = H, H2NC = (NH); Xaa = Gly, Sar, D-Ala; Y = OH, OCH3, NH2) were prepared by traditional methods in solution and tested for opioid activity. In binding studies based on displacement of mu, delta, and kappa opioid receptor selective radiolabels from guinea pig brain membranes, the new analogues showed a negligible affinity for the kappa binding site and a preference for mu- over delta-receptors with an evident dependence on N- and/or C-terminal modifications; H-Tyr-D-MetO-Phe-Gly-OCH3 was shown to be one of the most selective mu-receptor ligands reported to date. All these tetrapeptides display dose-related naloxone-reversible antinociceptive effects following intracerebroventricular (icv) or subcutaneous (sc) administrations in mice. In comparison to morphine, H-Tyr-D-MetO-Phe-Sar-NH2 and the guanidino derivative H2NC = (NH)-Tyr-D-MetO-Phe-Gly-NH2 showed lower affinity for mu, delta, and kappa sites but exceptionally stronger analgesia: respectively they are 560 and 1550 times as potent an analgesic as morphine. Among analogues tested after sc administration, H-Tyr-D-MetO-Phe-Sar-NH2 and H-Tyr-D-MetO-Phe-D-Ala-OH displayed the highest activities; they were respectively 22 and 30 times more potent than morphine on a molar basis. These results indicate that N- or C-terminal modifications and substitution at position 2 or 4 of dermorphin-(1-4) peptide do not only influence the affinity of the resulting analogues to opioid receptors but also may favorably alter their pharmacokinetic properties.

  DOI：

  10.1021/jm00392a002

文献信息

• MARASTONI, MAURO;SALVADORI, SEVEO;SEVERO;GIANFRANCO;BOREA, PIER ANDREA;MA+, J. MED. CHEM., 30,(1987) N 9, 1538-1542
  作者：MARASTONI, MAURO、SALVADORI, SEVEO、SEVERO、GIANFRANCO、BOREA, PIER ANDREA、MA+

  DOI：——

  日期：——