5-(Benzo[d][1,3]dioxol-5-yl)-6-ethynylpyrimidin-4-amine | 926009-17-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 5-(Benzo[d][1,3]dioxol-5-yl)-6-ethynylpyrimidin-4-amine
• 英文别名: 5-(1,3-benzodioxol-5-yl)-6-ethynylpyrimidin-4-amine
• CAS: 926009-17-8
• 化学式: C₁₃H₉N₃O₂
• 分子量: 239.233
• InChiKey: NVDFSVMYGWTOLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(Benzo[d][1,3]dioxol-5-yl)-6-ethynylpyrimidin-4-amine 、 [5-iodo-2-(morpholin-4-yl)pyridin-4-yl](2-methoxyethyl)methylamine 在 bis-triphenylphosphine-palladium(II) chloride copper(l) iodide 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以11%的产率得到5-Benzo[1,3]dioxol-5-yl-6-{4-[(2-methoxyethyl)-methylamino]-6-morpholin-4-ylpyridin-3-ylethynyl}pyrimidin-4-ylamine
  参考文献：
  名称：

  4-Amino-5-aryl-6-arylethynylpyrimidines: Structure–activity relationships of non-nucleoside adenosine kinase inhibitors

  摘要：

  A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-yipyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.029
• 作为产物：
  描述：

  5-(benzo[1,3]dioxol-5-yl)pyrimidine-4,6-diol 在 bis-triphenylphosphine-palladium(II) chloride ammonium hydroxide 、 copper(l) iodide 、 氢碘酸 、 potassium carbonate 、 三乙胺 、 sodium iodide 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 110.25h， 生成 5-(Benzo[d][1,3]dioxol-5-yl)-6-ethynylpyrimidin-4-amine
  参考文献：
  名称：

  4-Amino-5-aryl-6-arylethynylpyrimidines: Structure–activity relationships of non-nucleoside adenosine kinase inhibitors

  摘要：

  A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-yipyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.029

文献信息

• 4-Amino-5-aryl-6-arylethynylpyrimidines: Structure–activity relationships of non-nucleoside adenosine kinase inhibitors
  作者：Mark A. Matulenko、Ernest S. Paight、Robin R. Frey、Arthur Gomtsyan、Stanley DiDomenico、Meiqun Jiang、Chih-Hung Lee、Andrew O. Stewart、Haixia Yu、Kathy L. Kohlhaas、Karen M. Alexander、Steve McGaraughty、Joseph Mikusa、Kennan C. Marsh、Steven W. Muchmore、Clarissa L. Jakob、Elizabeth A. Kowaluk、Michael F. Jarvis、Shripad S. Bhagwat

  DOI：10.1016/j.bmc.2006.12.029

  日期：2007.2

  A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-yipyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed. (c) 2006 Elsevier Ltd. All rights reserved.