H-Tyr-D-MetO-Phe-Gly-NH2 | 100572-16-5

• 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: H-Tyr-D-MetO-Phe-Gly-NH2
• 英文别名: H-Tyr-D-Met(O)-Phe-Gly-NH2；(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-1-oxo-3-phenylpropan-2-yl]-4-methylsulfinylbutanamide
• CAS: 100572-16-5
• 化学式: C₂₅H₃₃N₅O₆S
• 分子量: 531.633
• InChiKey: FMRTYTBONSAXIF-BFDUOTSHSA-N

物化性质

• 沸点：
  1045.9±65.0 °C(Predicted)
• 密度：
  1.342±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  37
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  213
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  H-Tyr-D-MetO-Phe-Gly-NH2 、 1-amidino-3,5-dimethylpyrazole acetate 生成 (R)-N-[(S)-1-(Carbamoylmethyl-carbamoyl)-2-phenyl-ethyl]-2-[(S)-2-guanidino-3-(4-hydroxy-phenyl)-propionylamino]-4-methanesulfinyl-butyramide; compound with 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
• 作为产物：
  描述：

  H-Phe-Gly-OMe 在 ethandithiol 、 ammonium hydroxide 、 sodium hydroxide 、 双氧水 、 溶剂黄146 、 苯甲醚 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.5h， 生成 H-Tyr-D-MetO-Phe-Gly-NH2
  参考文献：
  名称：

  A Synthetic Method Suitable for the Rapid Preparation of 13N-Labeled Dermorphin Analogue, H-Tyr-D-Met(O)-Phe-Gly-NH2 (SD-62).

  摘要：

  建立了一种适合于制备13N标记的德吗啡类似物H-Tyr-D-Met(O)-Phe-Gly-NH2（SD-62）的合成方法，即用氨水处理活性酯前体5分钟合成SD-62。用这种方法制备的 13N 标记的 SD-62 与[13]氨一起给小鼠注射时，放射性在大脑中积累的时间曲线与镇痛活性的时间曲线非常吻合。

  DOI：

  10.1248/cpb.39.2734

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：——
• Synthesis and activity profiles of new dermorphin-(1-4) peptide analogs
  作者：Mauro Marastoni、Severo Salvadori、Gianfranco Balboni、Pier Andrea Borea、Giuliano Marzola、Roberto Tomatis

  DOI：10.1021/jm00392a002

  日期：1987.9

  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.
• A Synthetic Method Suitable for the Rapid Preparation of 13N-Labeled Dermorphin Analogue, H-Tyr-D-Met(O)-Phe-Gly-NH2 (SD-62).
  作者：Yoshiaki KISO、Satoshi IINUMA、Tsutomu MIMOTO、Hideo SAJI、Akira YOKOYAMA、Kenichi AKAJI

  DOI：10.1248/cpb.39.2734

  日期：——

  A synthetic method suitable for the preparation of 13N-labeled dermorphin analogue, H-Tyr-D-Met(O)-Phe-Gly-NH2 (SD-62), was established; i.e., SD-62 was synthesized by a 5 min treatment of the active ester precursor with ammonia. When the 13N-labeled SD-62, prepared by this method with [13]ammonia, was administered into mice, the time profile of the radioactivity accumulation in the brain paralleled well that of the analgesic activity.

  建立了一种适合于制备13N标记的德吗啡类似物H-Tyr-D-Met(O)-Phe-Gly-NH2（SD-62）的合成方法，即用氨水处理活性酯前体5分钟合成SD-62。用这种方法制备的 13N 标记的 SD-62 与[13]氨一起给小鼠注射时，放射性在大脑中积累的时间曲线与镇痛活性的时间曲线非常吻合。