TFA*Tyr-cyclo(4(S)-NH-Pro-Phe-Phe) | 1365260-25-8

• 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: TFA*Tyr-cyclo(4(S)-NH-Pro-Phe-Phe)
• 英文别名: (1S,4S,7S,10S)-11-[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]-4,7-dibenzyl-2,5,8,11-tetrazabicyclo[8.2.1]tridecane-3,6,9-trione;2,2,2-trifluoroacetic acid
• CAS: 1365260-25-8
• 化学式: C₂HF₃O₂*C₃₂H₃₅N₅O₅
• 分子量: 683.684
• InChiKey: ITNOYRFWEHJMOH-LWHRXMGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.45
• 重原子数：
  49
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  191
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (S)-methyl 2-((S)-2-(tert-butoxycarbonylamino)-3-phenylpropanamido)-3-phenylpropanoate 在 N-甲基吗啉 、 palladium 10% on activated carbon 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 1-羟基苯并三唑 、 1,2-二氯乙烷 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 TFA*Tyr-cyclo(4(S)-NH-Pro-Phe-Phe)
  参考文献：
  名称：

  Thecis-4-Amino-l-proline Residue as a Scaffold for the Synthesis of Cyclic and Linear Endomorphin-2 Analogues

  摘要：

  Endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) is an endogenous tetrapeptide that combines potency and efficacy with high affinity and selectivity toward the mu opioid receptor, the most responsible for analgesic effects in the central nervous system. The presence of the Pro(2) represents a crucial factor for the ligand structural and conformational properties. Praline is in fact an efficient stereochemical spacer, capable of inducing favorable spatial orientation of aromatic rings, a key factor for ligand recognition and interaction with receptors. Here the Pro(2) has been replaced by 4(S)-NH2-2(S)-proline (cAmp), a proline/GABA cis-chimera residue. This bivalent amino acid maintains the capacity to influenc the tetrapeptide conformation and offers the opportunity to generate new linear models and unusually constrained cyclic analogues characterized by an N-terminal Tyr bearing a free alpha-amino group. The results indicate that the new analogues do not show affinity for both delta and kappa opioid receptors and bind only poorly to the mu receptors (for cyclopeptide 9: K-i(mu) = 660 nM; GPI (IC50) = 1.4% at 1 mu M; for linear tetrapeptide acid 13: K-i(mu) = 2000 nM; GPI (IC50) = 0% at 1 mu M; for linear tetrapeptide amide 15: K-i(mu) = 310 nM; GPI (IC50) = 894 nM).

  DOI：

  10.1021/jm201402v

文献信息

• The<i>cis</i>-4-Amino-<scp>l</scp>-proline Residue as a Scaffold for the Synthesis of Cyclic and Linear Endomorphin-2 Analogues
  作者：Adriano Mollica、Francesco Pinnen、Azzurra Stefanucci、Federica Feliciani、Cristina Campestre、Luisa Mannina、Anatoly P. Sobolev、Gino Lucente、Peg Davis、Josephine Lai、Shou-Wu Ma、Frank Porreca、Victor J. Hruby

  DOI：10.1021/jm201402v

  日期：2012.4.12

  Endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) is an endogenous tetrapeptide that combines potency and efficacy with high affinity and selectivity toward the mu opioid receptor, the most responsible for analgesic effects in the central nervous system. The presence of the Pro(2) represents a crucial factor for the ligand structural and conformational properties. Praline is in fact an efficient stereochemical spacer, capable of inducing favorable spatial orientation of aromatic rings, a key factor for ligand recognition and interaction with receptors. Here the Pro(2) has been replaced by 4(S)-NH2-2(S)-proline (cAmp), a proline/GABA cis-chimera residue. This bivalent amino acid maintains the capacity to influenc the tetrapeptide conformation and offers the opportunity to generate new linear models and unusually constrained cyclic analogues characterized by an N-terminal Tyr bearing a free alpha-amino group. The results indicate that the new analogues do not show affinity for both delta and kappa opioid receptors and bind only poorly to the mu receptors (for cyclopeptide 9: K-i(mu) = 660 nM; GPI (IC50) = 1.4% at 1 mu M; for linear tetrapeptide acid 13: K-i(mu) = 2000 nM; GPI (IC50) = 0% at 1 mu M; for linear tetrapeptide amide 15: K-i(mu) = 310 nM; GPI (IC50) = 894 nM).