(S)-N-((S)-1-((S)-1-amino-1-oxo-3-phenylpropan-2-ylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl)-1-((S)-2-(2-aminooctanamido)-3-(4-hydroxyphenyl)propanoyl)pyrrolidine-2-carboxamide | 952227-72-4

• 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: (S)-N-((S)-1-((S)-1-amino-1-oxo-3-phenylpropan-2-ylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl)-1-((S)-2-(2-aminooctanamido)-3-(4-hydroxyphenyl)propanoyl)pyrrolidine-2-carboxamide
• 英文别名: (2S)-1-[(2S)-2-(2-aminooctanoylamino)-3-(4-hydroxyphenyl)propanoyl]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pyrrolidine-2-carboxamide
• CAS: 952227-72-4
• 化学式: C₄₂H₅₃N₇O₆
• 分子量: 751.926
• InChiKey: ISXFTRWXVQNDLR-OINPDUSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  55
• 可旋转键数：
  19
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  213
• 氢给体数：
  7
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-((tertbutoxycarbonyl)amino)octanoic acid 、 Fmoc-L-脯氨酸 、 Fmoc-O-叔丁基-L-酪氨酸 、 Fmoc-L-色氨酸(Boc)-OH 、 alkaline earth salt of/the/ methylsulfuric acid 以9.8%的产率得到(S)-N-((S)-1-((S)-1-amino-1-oxo-3-phenylpropan-2-ylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl)-1-((S)-2-(2-aminooctanamido)-3-(4-hydroxyphenyl)propanoyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Synthesis and in vitro evaluation of a library of modified endomorphin 1 peptides

  摘要：

  Endomorphin 1 (Endo-1 = Tyr-Pro-Trp-Phe-NH(2)), an endogenous opioid with high affinity and selectivity for mu-opioid receptors, mediates acute and neuropathic pain in rodents. To overcome metabolic instability and poor membrane permeability, the N- and C-termini of Endo-1 were modified by lipoamino acids (Laa) and/or sugars, and 2',6'-dimethyltyrosine (Dmt) replacement of Tyr. Analogues were assessed for mu-opioid receptor affinity, inhibition of cAMP accumulation, enzymatic stability, and permeability across Caco-2 cell monolayers. C-Terminus modi. cation decreased receptor affinity, while N-terminus C8-Laa improved stability and permeability with slight change in receptor affinity. Dmt provided a promising lead compound: [C8Laa-Dmt[1]]-Endo-1 is nine times more stable (t(1/2) = 43.5 min), >8- fold more permeable in Caco-2 cell monolayers, and exhibits 140-fold greater mu-opioid receptor affinity (K(i mu) = 0.08 nM). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.04.020