methyl (S)-2-[(S)-2-(4-isobutylphenyl)propanamido]-3-(4-tertbutoxyphenyl)propanoate | 1190366-67-6

• 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: methyl (S)-2-[(S)-2-(4-isobutylphenyl)propanamido]-3-(4-tertbutoxyphenyl)propanoate
• 英文别名: methyl (2S)-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]-2-[[(2S)-2-[4-(2-methylpropyl)phenyl]propanoyl]amino]propanoate
• CAS: 1190366-67-6
• 化学式: C₂₇H₃₇NO₄
• 分子量: 439.595
• InChiKey: KAMQTHINDWMYKJ-CYFREDJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (S)-2-[(S)-2-(4-isobutylphenyl)propanamido]-3-(4-tertbutoxyphenyl)propanoate 在 lithium hydroxide monohydrate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.5h， 生成
  参考文献：
  名称：

  DEPBT as Coupling Reagent To Avoid Racemization in a Solution-Phase Synthesis of a Kyotorphin Derivative

  摘要：

  The synthesis of IbKTP-NH2 with reduction of racemization up to no detectable level has been achieved using 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT). Among all coupling systems tested, only DEPBT-mediated amide bond formation between N-alpha-acylated tyrosine and arginine without loss of optical purity.

  DOI：

  10.1055/s-0033-1341068
• 作为产物：
  描述：

  (S)-(+)-布洛芬 、 邻叔丁基- L-酪氨酸甲酯盐酸盐 在 N-甲基吗啉 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以95%的产率得到methyl (S)-2-[(S)-2-(4-isobutylphenyl)propanamido]-3-(4-tertbutoxyphenyl)propanoate
  参考文献：
  名称：

  DEPBT as Coupling Reagent To Avoid Racemization in a Solution-Phase Synthesis of a Kyotorphin Derivative

  摘要：

  The synthesis of IbKTP-NH2 with reduction of racemization up to no detectable level has been achieved using 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT). Among all coupling systems tested, only DEPBT-mediated amide bond formation between N-alpha-acylated tyrosine and arginine without loss of optical purity.

  DOI：

  10.1055/s-0033-1341068

文献信息

• Chemical Conjugation of the Neuropeptide Kyotorphin and Ibuprofen Enhances Brain Targeting and Analgesia
  作者：Marta M. B. Ribeiro、Antónia R. T. Pinto、Marco M. Domingues、Isa Serrano、Montserrat Heras、Eduard R. Bardaji、Isaura Tavares、Miguel A. Castanho

  DOI：10.1021/mp2003016

  日期：2011.10.3

  The pharmaceutical potential of natural analgesic, peptides is mainly hampered by their inability to cross the blood-brain barrier, BBB. Increasing peptide-cell membrane Ibuprofen affinity through drug design is a promising strategy to overcome this limitation. To address this challenge, we grafted ibuprofen (IBP), a nonsteroidal anti-inflammatory drug, to kyotorphin (L-Tyr-L-Arg, KTP), an analgesic neuropeptide unable to cross BBB. Two new KTP derivatives, IBP-KTP (IbKTP-OH) and IBP-KTP-amide (IbKTP-NH2), were synthesized and characterized for membrane interaction, analgesic activity and mechanism of action. Ibuprofen enhanced peptide-membrane interaction, endowing a specificity for anionic fluid bilayers. A direct correlation between anionic lipid affinity and analgesic effect was established, IbKTP-NH2 being the most potent analgesic (from 25 mu mol.kg(-1)). In vitro, IbKTP-NH2 caused the biggest shift in the membrane surface charge of BBB endothelial cells, as quantified using zeta-potential dynamic light scattering. Our results suggest that IbKTP-NH2 crosses the BBB and acts by activating both opioid dependent and independent pathways.