(S)-3-tert-Butoxycarbonylamino-N-[3-((S)-1-{[2-(3,4-dichloro-phenyl)-acetyl]-methyl-amino}-2-pyrrolidin-1-yl-ethyl)-phenyl]-succinamic acid benzyl ester | 182196-97-0

• 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)-3-tert-Butoxycarbonylamino-N-[3-((S)-1-{[2-(3,4-dichloro-phenyl)-acetyl]-methyl-amino}-2-pyrrolidin-1-yl-ethyl)-phenyl]-succinamic acid benzyl ester
• 英文别名: benzyl (3S)-4-[3-[(1S)-1-[[2-(3,4-dichlorophenyl)acetyl]-methylamino]-2-pyrrolidin-1-ylethyl]anilino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate
• CAS: 182196-97-0
• 化学式: C₃₇H₄₄Cl₂N₄O₆
• 分子量: 711.686
• InChiKey: SSGWNAMYHNQMCN-AJQTZOPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  49
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-3-tert-Butoxycarbonylamino-N-[3-((S)-1-{[2-(3,4-dichloro-phenyl)-acetyl]-methyl-amino}-2-pyrrolidin-1-yl-ethyl)-phenyl]-succinamic acid benzyl ester 在 palladium on activated charcoal 盐酸 、 氢气 、 溶剂黄146 、 苯甲醚 作用下， 以 甲醇 为溶剂， 反应 1.66h， 生成
  参考文献：
  名称：

  Aspartic Acid Conjugates of 2-(3,4-Dichlorophenyl)-N-methyl-N- [(1S)-1-(3-aminophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide:  κ Opioid Receptor Agonists with Limited Access to the Central Nervous System

  摘要：

  Aspartic acid conjugates of 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3-aminophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide (5) were synthesized and evaluated in mice for antinociceptive activity by intravenous and intracerebroventricular routes of administration. The intravenously-administered alpha-conjugate of L-Asp (2), its D-Asp diastereomer (3), and the beta-conjugate of L-Asp (4) were found to be 11-, 31-, and 40-fold, respectively, less effective than the parent ligand 1 (ICI 199,441) in producing central nervous system mediated antinociception in the mouse abdominal stretch assay. In addition, iv-administered 2 and 3 were found to also produce potent antinociception in the tonic phase of the mouse formalin assay, which is a model of tonic rather than acute pain. This study suggests that the attachment of a zwitterionic moiety to a position in the molecule that exhibits bulk tolerance is a viable strategy for the design of peripherally-selective and peripherally-active opioids.

  DOI：

  10.1021/jm960459x
• 作为产物：
  描述：

  Boc-L-天冬氨酸 4-苄酯 、 N-[(1S)-1-(3-aminophenyl)-2-(pyrrolidin-1-yl)ethyl]-2-(3,4-dichlorophenyl)-N-methylacetamide 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 生成 (S)-3-tert-Butoxycarbonylamino-N-[3-((S)-1-{[2-(3,4-dichloro-phenyl)-acetyl]-methyl-amino}-2-pyrrolidin-1-yl-ethyl)-phenyl]-succinamic acid benzyl ester
  参考文献：
  名称：

  Aspartic Acid Conjugates of 2-(3,4-Dichlorophenyl)-N-methyl-N- [(1S)-1-(3-aminophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide:  κ Opioid Receptor Agonists with Limited Access to the Central Nervous System

  摘要：

  Aspartic acid conjugates of 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3-aminophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide (5) were synthesized and evaluated in mice for antinociceptive activity by intravenous and intracerebroventricular routes of administration. The intravenously-administered alpha-conjugate of L-Asp (2), its D-Asp diastereomer (3), and the beta-conjugate of L-Asp (4) were found to be 11-, 31-, and 40-fold, respectively, less effective than the parent ligand 1 (ICI 199,441) in producing central nervous system mediated antinociception in the mouse abdominal stretch assay. In addition, iv-administered 2 and 3 were found to also produce potent antinociception in the tonic phase of the mouse formalin assay, which is a model of tonic rather than acute pain. This study suggests that the attachment of a zwitterionic moiety to a position in the molecule that exhibits bulk tolerance is a viable strategy for the design of peripherally-selective and peripherally-active opioids.

  DOI：

  10.1021/jm960459x

文献信息

• Aspartic Acid Conjugates of 2-(3,4-Dichlorophenyl)-<i>N</i>-methyl-<i>N</i>- [(1<i>S</i>)-1-(3-aminophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide:  κ Opioid Receptor Agonists with Limited Access to the Central Nervous System
  作者：An-Chih Chang、Alan Cowan、Akira E. Takemori、Philip S. Portoghese

  DOI：10.1021/jm960459x

  日期：1996.1.1

  Aspartic acid conjugates of 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3-aminophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide (5) were synthesized and evaluated in mice for antinociceptive activity by intravenous and intracerebroventricular routes of administration. The intravenously-administered alpha-conjugate of L-Asp (2), its D-Asp diastereomer (3), and the beta-conjugate of L-Asp (4) were found to be 11-, 31-, and 40-fold, respectively, less effective than the parent ligand 1 (ICI 199,441) in producing central nervous system mediated antinociception in the mouse abdominal stretch assay. In addition, iv-administered 2 and 3 were found to also produce potent antinociception in the tonic phase of the mouse formalin assay, which is a model of tonic rather than acute pain. This study suggests that the attachment of a zwitterionic moiety to a position in the molecule that exhibits bulk tolerance is a viable strategy for the design of peripherally-selective and peripherally-active opioids.