2-(1H-indol-3-yl)-2-oxo-N-(pyridin-3-ylmethyl)acetamide

• 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-(1H-indol-3-yl)-2-oxo-N-(pyridin-3-ylmethyl)acetamide
• 化学式: C₁₆H₁₃N₃O₂
• 分子量: 279.298
• InChiKey: XMDUWLAFQRDJON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  74.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氨甲基吡啶 、 吲哚-3-乙醛酰氯 在 三乙胺 作用下， 以 甲苯 为溶剂， 以71%的产率得到2-(1H-indol-3-yl)-2-oxo-N-(pyridin-3-ylmethyl)acetamide
  参考文献：
  名称：

  Refinement of the Benzodiazepine Receptor Site Topology by Structure−Activity Relationships of New N-(Heteroarylmethyl)indol-3-ylglyoxylamides

  摘要：

  N-(Heteroaryiniethyl)indol-3-ylglyoxylamides (1-26) were synthesized and evaluated as ligands of the benzodiazepine receptor (BzR) to probe the hydrogen bonding properties of the so-called S, site of the BzR by means of suitable heterocyclic side chains. SARs were developed in light of our hypothesis of binding modes A and B. Pyrrole and furan derivatives adopting mode A (2, 8, 10, 20, 22) turned out to be more potent (K-i values < 35 nM) than their analogues lacking hydrogen bonding heterocyclic side chains. These data suggest that the most potent indoles interact with a hydrogen bond acceptor/donor (HBA/D) group located within the S, site of the BzR. Compounds 1, 2, 8, 19, 20, and 22, tested at recombinant rat (alpha(1)beta(2)gamma(2),, alpha(2)beta(2)gamma(2), and alpha(5)beta(3)gamma(2) BzRs, elicited selectivity for the alpha(1)beta(2)gamma(2) isoform. On the basis of published mutagenesis studies and the present SARs, we speculate that the S, HBA/D group might be identified as the hydroxyl of alpha(1)-Tyr209 or of other neighboring amino acids.

  DOI：

  10.1021/jm0511841

文献信息

• Refinement of the Benzodiazepine Receptor Site Topology by Structure−Activity Relationships of New <i>N</i>-(Heteroarylmethyl)indol-3-ylglyoxylamides
  作者：Giampaolo Primofiore、Federico Da Settimo、Anna Maria Marini、Sabrina Taliani、Concettina La Motta、Francesca Simorini、Ettore Novellino、Giovanni Greco、Barbara Cosimelli、Marina Ehlardo、Annalisa Sala、François Besnard、Marina Montali、Claudia Martini

  DOI：10.1021/jm0511841

  日期：2006.4.1

  N-(Heteroaryiniethyl)indol-3-ylglyoxylamides (1-26) were synthesized and evaluated as ligands of the benzodiazepine receptor (BzR) to probe the hydrogen bonding properties of the so-called S, site of the BzR by means of suitable heterocyclic side chains. SARs were developed in light of our hypothesis of binding modes A and B. Pyrrole and furan derivatives adopting mode A (2, 8, 10, 20, 22) turned out to be more potent (K-i values < 35 nM) than their analogues lacking hydrogen bonding heterocyclic side chains. These data suggest that the most potent indoles interact with a hydrogen bond acceptor/donor (HBA/D) group located within the S, site of the BzR. Compounds 1, 2, 8, 19, 20, and 22, tested at recombinant rat (alpha(1)beta(2)gamma(2),, alpha(2)beta(2)gamma(2), and alpha(5)beta(3)gamma(2) BzRs, elicited selectivity for the alpha(1)beta(2)gamma(2) isoform. On the basis of published mutagenesis studies and the present SARs, we speculate that the S, HBA/D group might be identified as the hydroxyl of alpha(1)-Tyr209 or of other neighboring amino acids.