1-N^α-Boc-Dmt-amino-4-(N^α-Fmoc-Phe-amino)butane | 573703-30-7

• 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: 1-N^α-Boc-Dmt-amino-4-(N^α-Fmoc-Phe-amino)butane
• 英文别名: tert-butyl N-[(2S)-1-[4-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-phenylpropanoyl]amino]butylamino]-3-(4-hydroxy-2,6-dimethylphenyl)-1-oxopropan-2-yl]carbamate
• CAS: 573703-30-7
• 化学式: C₄₄H₅₂N₄O₇
• 分子量: 748.919
• InChiKey: GPLXUOXLVLFOJF-YDAXCOIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  55
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  155
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-N^α-Boc-Dmt-amino-4-(N^α-Fmoc-Phe-amino)butane 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 [(S)-1-[4-((S)-2-Amino-3-phenyl-propionylamino)-butylcarbamoyl]-2-(4-hydroxy-2,6-dimethyl-phenyl)-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Unique High-Affinity Synthetic μ-Opioid Receptor Agonists with Central- and Systemic-Mediated Analgesia

  摘要：

  Unique opioid mimetic substances containing identical N-terminal aromatic residues separated by an unbranched alkyl chain containing two to eight methylene groups were developed. Regardless of the length of interposing alkyl chain, the bis-Tyr and bis-Phe compounds were inactive; however, replacement by a single Dint (2',6'-dimethyl-L-tyrosine) residue enhanced activity by orders of magnitude. Moreover, the bis-Dmt compounds were another 10-fold more potent with an optimum intra-aromatic ring distance of about four to six methylene units. 1,4-Bis(Dmt-NH)butane (7) had high mu-opioid receptor affinity (K-i = 0.041 nM) and functional mu-opioid agonist bioactivity (IC50 = 5.3 nM) with in vivo central (intracerebroventricular) and systemic (subcutaneous) analgesia in mice (1.5- to 2.5-fold greater than and 10-12% relative to morphine, respectively); these activities were reversed by naloxone to the same degree. It appears that the bis-Dmt compounds indiscriminately act as both message and address domains.

  DOI：

  10.1021/jm020459z
• 作为产物：
  描述：

  N-Boc-2,6-二甲基-L-酪氨酸 、 1-amino-4-(N^α-Fmoc-Phe-amino)butane trifluoroacetate 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以63%的产率得到1-N^α-Boc-Dmt-amino-4-(N^α-Fmoc-Phe-amino)butane
  参考文献：
  名称：

  Unique High-Affinity Synthetic μ-Opioid Receptor Agonists with Central- and Systemic-Mediated Analgesia

  摘要：

  Unique opioid mimetic substances containing identical N-terminal aromatic residues separated by an unbranched alkyl chain containing two to eight methylene groups were developed. Regardless of the length of interposing alkyl chain, the bis-Tyr and bis-Phe compounds were inactive; however, replacement by a single Dint (2',6'-dimethyl-L-tyrosine) residue enhanced activity by orders of magnitude. Moreover, the bis-Dmt compounds were another 10-fold more potent with an optimum intra-aromatic ring distance of about four to six methylene units. 1,4-Bis(Dmt-NH)butane (7) had high mu-opioid receptor affinity (K-i = 0.041 nM) and functional mu-opioid agonist bioactivity (IC50 = 5.3 nM) with in vivo central (intracerebroventricular) and systemic (subcutaneous) analgesia in mice (1.5- to 2.5-fold greater than and 10-12% relative to morphine, respectively); these activities were reversed by naloxone to the same degree. It appears that the bis-Dmt compounds indiscriminately act as both message and address domains.

  DOI：

  10.1021/jm020459z

文献信息

• Unique High-Affinity Synthetic μ-Opioid Receptor Agonists with Central- and Systemic-Mediated Analgesia
  作者：Yoshio Okada、Yuko Tsuda、Yoshio Fujita、Toshio Yokoi、Yusuke Sasaki、Akihiro Ambo、Ryoji Konishi、Mitsuhiro Nagata、Severo Salvadori、Yunden Jinsmaa、Sharon D. Bryant、Lawrence H. Lazarus

  DOI：10.1021/jm020459z

  日期：2003.7.1

  Unique opioid mimetic substances containing identical N-terminal aromatic residues separated by an unbranched alkyl chain containing two to eight methylene groups were developed. Regardless of the length of interposing alkyl chain, the bis-Tyr and bis-Phe compounds were inactive; however, replacement by a single Dint (2',6'-dimethyl-L-tyrosine) residue enhanced activity by orders of magnitude. Moreover, the bis-Dmt compounds were another 10-fold more potent with an optimum intra-aromatic ring distance of about four to six methylene units. 1,4-Bis(Dmt-NH)butane (7) had high mu-opioid receptor affinity (K-i = 0.041 nM) and functional mu-opioid agonist bioactivity (IC50 = 5.3 nM) with in vivo central (intracerebroventricular) and systemic (subcutaneous) analgesia in mice (1.5- to 2.5-fold greater than and 10-12% relative to morphine, respectively); these activities were reversed by naloxone to the same degree. It appears that the bis-Dmt compounds indiscriminately act as both message and address domains.