2-<<(adamantan-2-yloxy)carbonyl>amino>-N-<1-(S)-(aminomethyl)-5-(3-o-tolylureido)pentyl>-3-(1H-indol-3-yl)-2-(S)-methylpropionamide | 166446-82-8

• 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: 2-<<(adamantan-2-yloxy)carbonyl>amino>-N-<1-(S)-(aminomethyl)-5-(3-o-tolylureido)pentyl>-3-(1H-indol-3-yl)-2-(S)-methylpropionamide
• 英文别名: 2-adamantyl N-[(2S)-1-[[(2S)-1-amino-6-[(2-methylphenyl)carbamoylamino]hexan-2-yl]amino]-3-(1H-indol-3-yl)-2-methyl-1-oxopropan-2-yl]carbamate
• CAS: 166446-82-8
• 化学式: C₃₇H₅₀N₆O₄
• 分子量: 642.842
• InChiKey: JAGUATOJPSNXLL-XFNVTOGNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  47
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  150
• 氢给体数：
  6
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  丁二酸酐 、 2-<<(adamantan-2-yloxy)carbonyl>amino>-N-<1-(S)-(aminomethyl)-5-(3-o-tolylureido)pentyl>-3-(1H-indol-3-yl)-2-(S)-methylpropionamide 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以39%的产率得到N-<2-<<2-(S)-<<(adamantan-2-yloxy)carbonyl>amino>-3-(1H-indol-3-yl)-2-(S)-methylpropionyl>amino>-6-(3-o-tolylureido)hexyl>succinamic acid
  参考文献：
  名称：

  Modification of Receptor Selectivity and Functional Activity in Cholecystokinin Peptoid Ligands

  摘要：

  Hybrid analogs of the cholecystokinin A (CCK-A) receptor selective tetrapeptide agonist Boc-Trp-Lys(Tac)-Asp-MePhe-NH2 (1, A-71623) and the CCK-B receptor selective antagonists PD-135118 (2) and CI-988 (3) were prepared. Incorporation of the Lys(Tac) side chain into 2 produced a moderately potent antagonist of CCK-8 in the isolated guinea pig gallbladder (GPGB). Incorporation of the Lys(Tac) side chain into 3 produced the novel agonist analog 7 (EC(50) = 28 nM in the GPGB) with excellent affinity for both human CCK-A (IC50 = 12 nM) and CCK-B (IC50 = 17 nM) receptors. Analog 7 was a full agonist (EC(50) = 3.5 nM) for calcium mobilization on CHO-K1 cells expressing hCCK-A receptors but a partial agonist on CHO-K1 cells expressing hCCK-B receptors, eliciting a weak agonist reponse (EC(50) = 2800 nM) and antagonizing CCK-8-induced calcium mobilization (K-B = 20 nM). Despite this unusual in vitro profile, analog 7 was a potent anorectic agent in rats (ED(50) = 30 nmol/kg) following intraperitoneal administration.

  DOI：

  10.1021/jm00017a022
• 作为产物：
  描述：

  N-alpha-叔丁氧羰基-L-赖氨酸 在 palladium on activated charcoal 盐酸 、 4-二甲氨基吡啶 、 sodium hydroxide 、 N-羟基丁二酰亚胺 、 lithium aluminium tetrahydride 、 sodium azide 、 ethylcarbodiimide hydrochloride 、 氢气 、 三乙胺 、 N,N-二异丙基乙胺 、 氯甲酸异丁酯 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 88.75h， 生成 2-<<(adamantan-2-yloxy)carbonyl>amino>-N-<1-(S)-(aminomethyl)-5-(3-o-tolylureido)pentyl>-3-(1H-indol-3-yl)-2-(S)-methylpropionamide
  参考文献：
  名称：

  Modification of Receptor Selectivity and Functional Activity in Cholecystokinin Peptoid Ligands

  摘要：

  Hybrid analogs of the cholecystokinin A (CCK-A) receptor selective tetrapeptide agonist Boc-Trp-Lys(Tac)-Asp-MePhe-NH2 (1, A-71623) and the CCK-B receptor selective antagonists PD-135118 (2) and CI-988 (3) were prepared. Incorporation of the Lys(Tac) side chain into 2 produced a moderately potent antagonist of CCK-8 in the isolated guinea pig gallbladder (GPGB). Incorporation of the Lys(Tac) side chain into 3 produced the novel agonist analog 7 (EC(50) = 28 nM in the GPGB) with excellent affinity for both human CCK-A (IC50 = 12 nM) and CCK-B (IC50 = 17 nM) receptors. Analog 7 was a full agonist (EC(50) = 3.5 nM) for calcium mobilization on CHO-K1 cells expressing hCCK-A receptors but a partial agonist on CHO-K1 cells expressing hCCK-B receptors, eliciting a weak agonist reponse (EC(50) = 2800 nM) and antagonizing CCK-8-induced calcium mobilization (K-B = 20 nM). Despite this unusual in vitro profile, analog 7 was a potent anorectic agent in rats (ED(50) = 30 nmol/kg) following intraperitoneal administration.

  DOI：

  10.1021/jm00017a022

文献信息

• Modification of Receptor Selectivity and Functional Activity in Cholecystokinin Peptoid Ligands
  作者：Milana Dezube、Elizabeth E. Sugg、Larry S. Birkemo、Dallas K. Croom、Robert W. Dougherty、Gregory N. Ervin、Mary K. Grizzle、Michael K. James、Michael F. Johnson

  DOI：10.1021/jm00017a022

  日期：1995.8

  Hybrid analogs of the cholecystokinin A (CCK-A) receptor selective tetrapeptide agonist Boc-Trp-Lys(Tac)-Asp-MePhe-NH2 (1, A-71623) and the CCK-B receptor selective antagonists PD-135118 (2) and CI-988 (3) were prepared. Incorporation of the Lys(Tac) side chain into 2 produced a moderately potent antagonist of CCK-8 in the isolated guinea pig gallbladder (GPGB). Incorporation of the Lys(Tac) side chain into 3 produced the novel agonist analog 7 (EC(50) = 28 nM in the GPGB) with excellent affinity for both human CCK-A (IC50 = 12 nM) and CCK-B (IC50 = 17 nM) receptors. Analog 7 was a full agonist (EC(50) = 3.5 nM) for calcium mobilization on CHO-K1 cells expressing hCCK-A receptors but a partial agonist on CHO-K1 cells expressing hCCK-B receptors, eliciting a weak agonist reponse (EC(50) = 2800 nM) and antagonizing CCK-8-induced calcium mobilization (K-B = 20 nM). Despite this unusual in vitro profile, analog 7 was a potent anorectic agent in rats (ED(50) = 30 nmol/kg) following intraperitoneal administration.