Boc-Tyr-D-Met-Phe-OH | 100572-39-2

• 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: Boc-Tyr-D-Met-Phe-OH
• 英文别名: (2S)-2-[[(2R)-2-[[(2S)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-phenylpropanoic acid
• CAS: 100572-39-2
• 化学式: C₂₈H₃₇N₃O₇S
• 分子量: 559.684
• InChiKey: JUAUQIWMULSPGS-VJBWXMMDSA-N

物化性质

• 沸点：
  872.8±65.0 °C(Predicted)
• 密度：
  1.253±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.88
• 重原子数：
  39.0
• 可旋转键数：
  13.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  154.06
• 氢给体数：
  5.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  Boc-Tyr-D-Met-Phe-OH 在 N-甲基吗啉 、 sodium hydroxide 、 双氧水 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 Boc-Tyr-D-Met(O)-Phe-Gly-OH
  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：

  Boc-Tyr-D-Met-Phe-OMe 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以3.8 g的产率得到Boc-Tyr-D-Met-Phe-OH
  参考文献：
  名称：

  Synthesis and opioid activity of dermorphin tetrapeptides bearing D-methionine S-oxide at position 2

  摘要：

  Eight new dermorphin tetrapeptides, X-Tyr-D-MetO-Phe-aa-Y (X = H, H2N = C(NH); aa = Gly, 2-aminoethanol, sarcosine; Y = NH2, NH-alkyl), were prepared and tested for opioid activity. They show dose-related naloxone-reversible opioid effects in vitro and in vivo. H-Tyr-D-MetO-Phe-Gly-NH2 (I) (guinea pig ileum IC50 = 13.6 nM; tail-flick ED50 = 1.97 pmol/mouse, icv, and 0.65 mumol/kg, sc), though less effective in the periphery, has central activities higher than those of dermorphin H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2. Following intracerebroventricular or subcutaneous administrations in mice, I is about respectively 1500 and 17 times as potent an analgesic as morphine.

  DOI：

  10.1021/jm00156a003

文献信息

• Stereospecificity of amino acid side chains in deltorphin defines binding to opioid receptors
  作者：Lawrence H. Lazarus、Severo Salvadori、Gianfranco Balboni、Roberto Tomatis、William E. Wilson

  DOI：10.1021/jm00085a009

  日期：1992.4

  [des-His4]deltorphin A and [des-His4] analogues containing consecutive D-amino acid replacements in the remaining residues exhibited weak binding to delta receptors and poor delta selectivity. Substitution of D-Met2 in deltorphin A by D-Ala or D-Nle decreased delta selectivities 3-6-fold through an elevation in mu affinities; however, the converse replacement, D-Met for D-Ala2 in deltorphin B, diminished

  一系列的deltorphin A的单个D-氨基酸替代类似物，其中一些与His4缺失结合，用于探测大鼠脑阿片受体对肽结合参数的侧链方向的改变。残基1、3和5中具有D-氨基酸的肽主要表现出对δ受体的亲和力降低（88-1200倍），相对于deltorphin A的选择性降低了13-64倍（Ki delta = 0.45 nM； Ki mu / Ki delta = 764）：位于N端“消息”域中的芳香族侧链Tyr1和Phe3和位于C端“地址”域中的Leu5芳基侧链似乎起着至关重要的作用赋予高增量亲和力和选择性。尽管D-His4仅将delta亲和力降低了6倍，选择性降低了4倍，他的似乎参与了两个域的组成部分：[des-His4] deltorphin A和[des-His4]类似物在其余残基中包含连续的D-氨基酸替代，表现出与δ受体的结合力弱和δ选择性差。D-Ala或D-Nle替代deltorphin
• 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：——