N^α-(tert-butyloxycarbonyl)-α-L-aspartyl-8-<4-<<<<(aminoethyl)amino>carbonyl>methyl>oxy>phenyl>-1,3-dipropylxanthine β-benzyl ester | 108744-21-4

• 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: N^α-(tert-butyloxycarbonyl)-α-L-aspartyl-8-<4-<<<<(aminoethyl)amino>carbonyl>methyl>oxy>phenyl>-1,3-dipropylxanthine β-benzyl ester
• 英文别名: benzyl (3S)-4-[2-[[2-[4-(2,6-dioxo-1,3-dipropyl-7H-purin-8-yl)phenoxy]acetyl]amino]ethylamino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate
• CAS: 108744-21-4
• 化学式: C₃₇H₄₇N₇O₉
• 分子量: 733.822
• InChiKey: JOVBIAUMLQSYSI-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  53.0
• 可旋转键数：
  17.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  204.74
• 氢给体数：
  4.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  N^α-(tert-butyloxycarbonyl)-α-L-aspartyl-8-<4-<<<<(aminoethyl)amino>carbonyl>methyl>oxy>phenyl>-1,3-dipropylxanthine β-benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 [(S)-2-{(S)-1-[(S)-1-(Carbamoylmethyl-carbamoyl)-2-phenyl-ethylcarbamoyl]-2-phenyl-ethylcarbamoyl}-1-(2-{2-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-phenoxy]-acetylamino}-ethylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester
  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
• 作为产物：
  描述：

  Boc-L-天门冬氨酸苄酯-Osu 、 3,7-二乙基-9-(4-(N-2-氨基乙基甲酰氨基甲氧基))苯基黄嘌呤 以 N,N-二甲基甲酰胺 为溶剂， 以100%的产率得到N^α-(tert-butyloxycarbonyl)-α-L-aspartyl-8-<4-<<<<(aminoethyl)amino>carbonyl>methyl>oxy>phenyl>-1,3-dipropylxanthine β-benzyl ester
  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：——