-butanedioic acid mono-2-<<3-(1H-indol-3-ylmethyl)-2-methyl-1-oxo-2-<<(tricyclo<3.3.1.1^3,7>dec-2-yloxy)carbonyl>amino>propyl>amino>-1-phenylethyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: -butanedioic acid mono-2-<<3-(1H-indol-3-ylmethyl)-2-methyl-1-oxo-2-<<(tricyclo<3.3.1.1^3,7>dec-2-yloxy)carbonyl>amino>propyl>amino>-1-phenylethyl ester
• 英文别名: [R-(RS,RS)]-butanedioic acid mono-2-[(3-(1H-indol-3-ylmethyl)-2-methyl-1-oxo-2-{[(tricyclo[3.3.1.1^3,7]dec-2-yloxy)carbonyl]amino}propyl)amino]-1-phenylethyl ester；4-[(1R)-2-[[(2R)-2-(2-adamantyloxycarbonylamino)-3-(1H-indol-3-yl)-2-methylpropanoyl]amino]-1-phenylethoxy]-4-oxobutanoic acid
• 化学式: C₃₅H₄₁N₃O₇
• 分子量: 615.726
• InChiKey: QSAQIPVKISWRAT-ZABPBAJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  147
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (R)-(-)-2-氯-1-苯乙醇 在 Lindlar's catalyst 4-二甲氨基吡啶 、 sodium azide 、 氢气 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 25.0~100.0 ℃ 、310.27 kPa 条件下， 反应 43.0h， 生成 -butanedioic acid mono-2-<<3-(1H-indol-3-ylmethyl)-2-methyl-1-oxo-2-<<(tricyclo<3.3.1.1^3,7>dec-2-yloxy)carbonyl>amino>propyl>amino>-1-phenylethyl ester
  参考文献：
  名称：

  Rationally designed ‘dipeptoid’ analogues of cholecystokinin (CCK): C-terminal structure-activity relationships of α-methyl tryptophan derivatives

  摘要：

  This paper outlines the synthesis and C-terminal structure-activity relationships (SAR) of a series of alpha-methyl tryptophanylphenethylamide analogues of the neuropeptide cholecystokinin (CCK). CCK-B and CCK-A receptor binding affinities of these analogues are described and the contributions of the various side chains on the phenethylamide moiety to binding affinity are discussed. Several of the compounds prepared have CCK-B receptor binding affinities similar to that found with the endogenous neuropeptide CCK-26-33 (sulphated) (CCK-B, IC50 = 0.3 nM) and are highly selective over the CCK-A receptor. Amongst the most potent of the compounds synthesized are [R-(R*,S*)]-beta-4[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]-amino]propyl]amino]benzenebutanoic acid 22, [R-(R*,S*)]-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl] thio]acetic acid 28a and [R-(R*,S*)]-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl]sulfonyl]acetic acid 32 which have CCK-B receptor binding affinities of IC50 = 0.3, 0.3 and 0.2 nM with CCK-A/B ratios of 220, 700 and 1000, respectively. CCK-B receptor selective ligands, 22, 28a and 32 were also shown to be potent antagonists in blocking pentagastrin-evoked excitation in neurons of the rat hypothalamic ventro-medial nucleus (VMN) with the K(e) values of 2.8, 23 and 5.9 nM, respectively.

  DOI：

  10.1016/0223-5234(93)90078-s

文献信息

• Rationally designed ‘dipeptoid’ analogues of cholecystokinin (CCK): C-terminal structure-activity relationships of α-methyl tryptophan derivatives
  作者：PR Boden、JM Eden、M Higginbottom、DR Hill、DC Horwell、JC Hunter、K Martin、MC Pritchard、RS Richardson、E Roberts

  DOI：10.1016/0223-5234(93)90078-s

  日期：1993.1

  This paper outlines the synthesis and C-terminal structure-activity relationships (SAR) of a series of alpha-methyl tryptophanylphenethylamide analogues of the neuropeptide cholecystokinin (CCK). CCK-B and CCK-A receptor binding affinities of these analogues are described and the contributions of the various side chains on the phenethylamide moiety to binding affinity are discussed. Several of the compounds prepared have CCK-B receptor binding affinities similar to that found with the endogenous neuropeptide CCK-26-33 (sulphated) (CCK-B, IC50 = 0.3 nM) and are highly selective over the CCK-A receptor. Amongst the most potent of the compounds synthesized are [R-(R*,S*)]-beta-4[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]-amino]propyl]amino]benzenebutanoic acid 22, [R-(R*,S*)]-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl] thio]acetic acid 28a and [R-(R*,S*)]-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]amino]propyl]amino]-3-phenylpropyl]sulfonyl]acetic acid 32 which have CCK-B receptor binding affinities of IC50 = 0.3, 0.3 and 0.2 nM with CCK-A/B ratios of 220, 700 and 1000, respectively. CCK-B receptor selective ligands, 22, 28a and 32 were also shown to be potent antagonists in blocking pentagastrin-evoked excitation in neurons of the rat hypothalamic ventro-medial nucleus (VMN) with the K(e) values of 2.8, 23 and 5.9 nM, respectively.