[(S)-5-(1H-Benzoimidazol-2-yl)-5-({(S)-2-[(S)-2-tert-butoxycarbonylamino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionyl]-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl}-amino)-pentyl]-carbamic acid benzyl ester | 912671-21-7

• 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: [(S)-5-(1H-Benzoimidazol-2-yl)-5-({(S)-2-[(S)-2-tert-butoxycarbonylamino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionyl]-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl}-amino)-pentyl]-carbamic acid benzyl ester
• CAS: 912671-21-7
• 化学式: C₄₆H₅₄N₆O₇
• 分子量: 802.971
• InChiKey: WZYUWKKWQPBWBL-MXVPUGLGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.23
• 重原子数：
  59.0
• 可旋转键数：
  14.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  174.98
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  [(S)-5-(1H-Benzoimidazol-2-yl)-5-({(S)-2-[(S)-2-tert-butoxycarbonylamino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionyl]-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl}-amino)-pentyl]-carbamic acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 1.5h， 生成 (S)-2-[(S)-2-Amino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionyl]-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [(S)-5-amino-1-(1H-benzoimidazol-2-yl)-pentyl]-amide; compound with trifluoro-acetic acid
  参考文献：
  名称：

  Effect of Lysine at C-Terminus of the Dmt-Tic Opioid Pharmacophore

  摘要：

  Substitution of Gly with side-chain-protected or unprotected Lys in lead compounds containing the opioid pharmacophore Dmt-Tic [H-Dmt-Tic-Gly-NH-CH2-Ph, A agonist/% antagonist; H-Dmt-Tic-Gly-NH-Ph, A agonist/% agonist; and H-Dmt-Tic-NH-CH2-Bid, delta agonist ( Bid) 1H-benzimidazole-2-yl)] yielded a new series of compounds endowed with distinct pharmacological activities. Compounds (1-10) included high delta- (K-i(delta) 0.068-0.64 nM) and mu-opioid affinities (K-i(u)) 0.13-5.50 nM), with a bioactivity that ranged from mu-opioid agonism {10, H-Dmt-Tic-NH-CH[(CH2)4-NH2]-Bid (IC50 GPI = 39.7 nM)} to a selective mu-opioid antagonist [3, H-Dmt-Tic-Lys-NH-CH2-Ph (pA(2)(mu) = 7.96)] and a selective mu-opioid antagonist [5, H-Dmt-Tic-Lys(Ac)-NH-Ph (pA(2)(delta) = 12.0)]. The presence of a Lys linker provides new lead compounds in the formation of opioid peptidomimetics containing the Dmt-Tic pharmacophore with distinct agonist and/or antagonist properties.

  DOI：

  10.1021/jm060741w
• 作为产物：
  描述：

  、 N-Boc-2,6-二甲基-L-酪氨酸 在 N-甲基吗啉 、 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， 反应 27.0h， 以91%的产率得到[(S)-5-(1H-Benzoimidazol-2-yl)-5-({(S)-2-[(S)-2-tert-butoxycarbonylamino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionyl]-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl}-amino)-pentyl]-carbamic acid benzyl ester
  参考文献：
  名称：

  Effect of Lysine at C-Terminus of the Dmt-Tic Opioid Pharmacophore

  摘要：

  Substitution of Gly with side-chain-protected or unprotected Lys in lead compounds containing the opioid pharmacophore Dmt-Tic [H-Dmt-Tic-Gly-NH-CH2-Ph, A agonist/% antagonist; H-Dmt-Tic-Gly-NH-Ph, A agonist/% agonist; and H-Dmt-Tic-NH-CH2-Bid, delta agonist ( Bid) 1H-benzimidazole-2-yl)] yielded a new series of compounds endowed with distinct pharmacological activities. Compounds (1-10) included high delta- (K-i(delta) 0.068-0.64 nM) and mu-opioid affinities (K-i(u)) 0.13-5.50 nM), with a bioactivity that ranged from mu-opioid agonism {10, H-Dmt-Tic-NH-CH[(CH2)4-NH2]-Bid (IC50 GPI = 39.7 nM)} to a selective mu-opioid antagonist [3, H-Dmt-Tic-Lys-NH-CH2-Ph (pA(2)(mu) = 7.96)] and a selective mu-opioid antagonist [5, H-Dmt-Tic-Lys(Ac)-NH-Ph (pA(2)(delta) = 12.0)]. The presence of a Lys linker provides new lead compounds in the formation of opioid peptidomimetics containing the Dmt-Tic pharmacophore with distinct agonist and/or antagonist properties.

  DOI：

  10.1021/jm060741w