(2S)-N-[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-2-[[2-[[(2S)-2-[[(2S)-2-[[2-[4-[[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]amino]phenyl]acetyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]-4-methylpentanamide | 108744-20-3

• 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: (2S)-N-[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-2-[[2-[[(2S)-2-[[(2S)-2-[[2-[4-[[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]amino]phenyl]acetyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]-4-methylpentanamide
• CAS: 108744-20-3
• 化学式: C₄₉H₆₁N₁₁O₁₀S
• 分子量: 996.157
• InChiKey: OOFGDKLZKHQJPO-HTDJBETHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  71
• 可旋转键数：
  25
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  339
• 氢给体数：
  10
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  物质P(7-11) 、 phenyl>acetic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以92%的产率得到(2S)-N-[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-2-[[2-[[(2S)-2-[[(2S)-2-[[2-[4-[[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]amino]phenyl]acetyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]-4-methylpentanamide
  参考文献：
  名称：

  Binary drugs: conjugates of purines and a peptide that bind to both adenosine and substance P receptors

  摘要：

  A "functionalized congener" approach to adenosine receptor antagonists has provided a means to synthesize highly potent peptide conjugates of 1,3-dialkylxanthines. The antagonist XAC, such a functionalized xanthine amine congener, has been attached to a segment derived from the neurotransmitter peptide substance P (SP) to form a binary drug that binds to both receptors with Ki values of 35 nM (central A1-adenosine) and 300 nM (striatal SP). Coupling of the functionalized adenosine agonist N6-[p-(carboxymethyl)phenyl]adenosine to an SP C-terminal peptide also resulted in a binary drug that binds to both receptors. The demonstration that the biochemical properties of two unrelated drugs, both of which act through binding at extracellular receptors, may be combined in the same molecule suggests a novel strategy for drug design. In principle, a combined effect of the two different substances that produce the same final effect (e.g., hypotension by adenosine agonists and by SP analogues) might occur in vivo. Adenosine analogues have analgesic properties, and the binary drug derived from substance P and adenosine agonists or antagonists might provide useful tools for probing interrelationships of SP pathways and sites for the antinociceptive action of adenosine.

  DOI：

  10.1021/jm00391a046

文献信息

• JACOBSON, K. A.;LIPKOWSKI, A. W.;MOODY, T. W.;PADGETT, W.;PIJL, E.;KIRK, +, J. MED. CHEM., 30,(1987) N 8, 1529-1532
  作者：JACOBSON, K. A.、LIPKOWSKI, A. W.、MOODY, T. W.、PADGETT, W.、PIJL, E.、KIRK, +

  DOI：——

  日期：——
• Binary drugs: conjugates of purines and a peptide that bind to both adenosine and substance P receptors
  作者：Kenneth A. Jacobson、Andrzej W. Lipkowski、Terry W. Moody、William Padgett、Evelyn Pijl、Kenneth L. Kirk、John W. Daly

  DOI：10.1021/jm00391a046

  日期：1987.8

  A "functionalized congener" approach to adenosine receptor antagonists has provided a means to synthesize highly potent peptide conjugates of 1,3-dialkylxanthines. The antagonist XAC, such a functionalized xanthine amine congener, has been attached to a segment derived from the neurotransmitter peptide substance P (SP) to form a binary drug that binds to both receptors with Ki values of 35 nM (central A1-adenosine) and 300 nM (striatal SP). Coupling of the functionalized adenosine agonist N6-[p-(carboxymethyl)phenyl]adenosine to an SP C-terminal peptide also resulted in a binary drug that binds to both receptors. The demonstration that the biochemical properties of two unrelated drugs, both of which act through binding at extracellular receptors, may be combined in the same molecule suggests a novel strategy for drug design. In principle, a combined effect of the two different substances that produce the same final effect (e.g., hypotension by adenosine agonists and by SP analogues) might occur in vivo. Adenosine analogues have analgesic properties, and the binary drug derived from substance P and adenosine agonists or antagonists might provide useful tools for probing interrelationships of SP pathways and sites for the antinociceptive action of adenosine.