4-(6-ethynylpyridazin-3-yl)morpholine | 926009-40-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(6-ethynylpyridazin-3-yl)morpholine
• 英文别名: 4-(6-Ethynylpyridazin-3-yl)morpholine
• CAS: 926009-40-7
• 化学式: C₁₀H₁₁N₃O
• 分子量: 189.217
• InChiKey: VJEFPLQJVITBNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  38.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(4-chlorophenyl)-6-iodopyrimidin-4-ylamine 、 4-(6-ethynylpyridazin-3-yl)morpholine 在 bis-triphenylphosphine-palladium(II) chloride copper(l) iodide 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以11%的产率得到5-(4-Chlorophenyl)-6-(6-morpholin-4-ylpyridazin-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：

  4-(6-氯哒嗪-3-基)吗啉 在 bis-triphenylphosphine-palladium(II) chloride copper(l) iodide 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 72.0h， 生成 4-(6-ethynylpyridazin-3-yl)morpholine
  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.