1-(Methoxymethoxy)-6-[1-(3-methoxypropyl)pyrrolo[2,3-b]pyridin-5-yl]-4-phenylpyridin-2-one | 1415388-33-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(Methoxymethoxy)-6-[1-(3-methoxypropyl)pyrrolo[2,3-b]pyridin-5-yl]-4-phenylpyridin-2-one
• 英文别名: 1-(methoxymethoxy)-6-[1-(3-methoxypropyl)pyrrolo[2,3-b]pyridin-5-yl]-4-phenylpyridin-2-one
• CAS: 1415388-33-8
• 化学式: C₂₄H₂₅N₃O₄
• 分子量: 419.48
• InChiKey: BSVTYOGOMRKQLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  65.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(Methoxymethoxy)-6-[1-(3-methoxypropyl)pyrrolo[2,3-b]pyridin-5-yl]-4-phenylpyridin-2-one 在 盐酸 、 乙二醇 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 以78%的产率得到1-Hydroxy-6-[1-(3-Methoxypropyl)-1h-Pyrrolo[2,3-B]pyridin-5-Yl]-4-Phenylpyridin-2(1h)-One
  参考文献：
  名称：

  Design and evaluation of azaindole-substituted N-hydroxypyridones as glyoxalase I inhibitors

  摘要：

  We conducted a high throughput screening for glyoxalase I (GLO1) inhibitors and identified 4,6-diphenyl-N-hydroxypyridone as a lead compound. Using a binding model of the lead and public X-ray coordinates of GLO1 enzymes complexed with glutathione analogues, we designed 4-(7-azaindole)-substituted 6-phenyl-N-hydroxypyridones. 7-Azaindole's 7-nitrogen was expected to interact with a water network, resulting in an interaction with the protein. We validated this inhibitor design by comparing its structure-activity relationship (SAR) with that of corresponding indole derivatives, by analyzing the binding mode with X-ray crystallography and by evaluating its thermodynamic binding parameters. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.045
• 作为产物：
  描述：

  2,6-二氯吡啶N-氧化物 在 bis-triphenylphosphine-palladium(II) chloride 、 (1,5-cyclooctadiene)(methoxy)iridium(I) dimer 、 sodium carbonate 、 联硼酸频那醇酯 、 4,4'-二叔丁基-2,2'-二吡啶 、 sodium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(Methoxymethoxy)-6-[1-(3-methoxypropyl)pyrrolo[2,3-b]pyridin-5-yl]-4-phenylpyridin-2-one
  参考文献：
  名称：

  Design and evaluation of azaindole-substituted N-hydroxypyridones as glyoxalase I inhibitors

  摘要：

  We conducted a high throughput screening for glyoxalase I (GLO1) inhibitors and identified 4,6-diphenyl-N-hydroxypyridone as a lead compound. Using a binding model of the lead and public X-ray coordinates of GLO1 enzymes complexed with glutathione analogues, we designed 4-(7-azaindole)-substituted 6-phenyl-N-hydroxypyridones. 7-Azaindole's 7-nitrogen was expected to interact with a water network, resulting in an interaction with the protein. We validated this inhibitor design by comparing its structure-activity relationship (SAR) with that of corresponding indole derivatives, by analyzing the binding mode with X-ray crystallography and by evaluating its thermodynamic binding parameters. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.045

文献信息

• Design and evaluation of azaindole-substituted N-hydroxypyridones as glyoxalase I inhibitors
  作者：Takashi Chiba、Jun Ohwada、Hiroshi Sakamoto、Takamitsu Kobayashi、Takaaki A. Fukami、Machiko Irie、Takaaki Miura、Kazuhiro Ohara、Hiroshi Koyano

  DOI：10.1016/j.bmcl.2012.10.045

  日期：2012.12

  We conducted a high throughput screening for glyoxalase I (GLO1) inhibitors and identified 4,6-diphenyl-N-hydroxypyridone as a lead compound. Using a binding model of the lead and public X-ray coordinates of GLO1 enzymes complexed with glutathione analogues, we designed 4-(7-azaindole)-substituted 6-phenyl-N-hydroxypyridones. 7-Azaindole's 7-nitrogen was expected to interact with a water network, resulting in an interaction with the protein. We validated this inhibitor design by comparing its structure-activity relationship (SAR) with that of corresponding indole derivatives, by analyzing the binding mode with X-ray crystallography and by evaluating its thermodynamic binding parameters. (C) 2012 Elsevier Ltd. All rights reserved.