di(ethylene glycol) di[3-(pyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether | 390799-80-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: di(ethylene glycol) di[3-(pyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether
• 英文别名: 3-Pyridin-3-yl-4-[2-[2-[(4-pyridin-3-yl-1,2,5-thiadiazol-3-yl)oxy]ethoxy]ethoxy]-1,2,5-thiadiazole
• CAS: 390799-80-1
• 化学式: C₁₈H₁₆N₆O₃S₂
• 分子量: 428.495
• InChiKey: RTXXMDMYHBLLNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  162
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  di(ethylene glycol) di[3-(pyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether 在 sodium tetrahydroborate 作用下， 以 甲醇 、 氯仿 、 丙酮 为溶剂， 反应 2.0h， 生成 1-[4-(1-Methyl-1,2,3,6-tetrahydro-5-pyridinyl)-1,2,5-thiadiazol-3-yloxy]-2-{2-[4-(1-methyl-1,2,3,6-tetrahydro-5-pyridinyl)-1,2,5-thiadiazol-3-yloxy]ethoxy}ethane
  参考文献：
  名称：

  Design, Synthesis, and Biological Characterization of Bivalent 1-Methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole Derivatives as Selective Muscarinic Agonists

  摘要：

  Selective muscarinic agonists could be useful in the treatment of neurological disorders such as Alzheimer's disease, schizophrenia, and chronic pain. Many muscarinic agonists have been developed, yet most exhibit at best limited functional selectivity for a given receptor subtype perhaps because of the high degree of sequence homology within the putative binding site, which appears to be buried within the transmembrane domains. Bivalent compounds containing essentially two agonist pharmacophores within the same molecule were synthesized and tested for receptor binding affinity and muscarinic agonist activity. A series of bis-1,2,5-thiadiazole derivatives of 1,2,5,6-tetrahydropyridine linked by an alkyloxy moiety exhibited very high affinity (K-i < 1 nM) and strong agonist activity. The degree of activity depended on the length of the linking alkyl group, which could be replaced by a poly(ethylene glycol) moiety, resulting in improved water solubility, binding affinity, and agonist potency.

  DOI：

  10.1021/jm0102405
• 作为产物：
  描述：

  3-氯-4-(吡啶-3-基)-1,2,5-噻二唑 、 二乙二醇 在 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 25.0h， 以99.2%的产率得到di(ethylene glycol) di[3-(pyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether
  参考文献：
  名称：

  Design, Synthesis, and Biological Characterization of Bivalent 1-Methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole Derivatives as Selective Muscarinic Agonists

  摘要：

  Selective muscarinic agonists could be useful in the treatment of neurological disorders such as Alzheimer's disease, schizophrenia, and chronic pain. Many muscarinic agonists have been developed, yet most exhibit at best limited functional selectivity for a given receptor subtype perhaps because of the high degree of sequence homology within the putative binding site, which appears to be buried within the transmembrane domains. Bivalent compounds containing essentially two agonist pharmacophores within the same molecule were synthesized and tested for receptor binding affinity and muscarinic agonist activity. A series of bis-1,2,5-thiadiazole derivatives of 1,2,5,6-tetrahydropyridine linked by an alkyloxy moiety exhibited very high affinity (K-i < 1 nM) and strong agonist activity. The degree of activity depended on the length of the linking alkyl group, which could be replaced by a poly(ethylene glycol) moiety, resulting in improved water solubility, binding affinity, and agonist potency.

  DOI：

  10.1021/jm0102405

文献信息

• Design, Synthesis, and Biological Characterization of Bivalent 1-Methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole Derivatives as Selective Muscarinic Agonists
  作者：W. G. Rajeswaran、Yang Cao、Xi-Ping Huang、Mary Elizabeth Wroblewski、Tracy Colclough、Selina Lee、Fenghua Liu、Peter I. Nagy、James Ellis、Beth A. Levine、Karl H. Nocka、William S. Messer

  DOI：10.1021/jm0102405

  日期：2001.12.1

  Selective muscarinic agonists could be useful in the treatment of neurological disorders such as Alzheimer's disease, schizophrenia, and chronic pain. Many muscarinic agonists have been developed, yet most exhibit at best limited functional selectivity for a given receptor subtype perhaps because of the high degree of sequence homology within the putative binding site, which appears to be buried within the transmembrane domains. Bivalent compounds containing essentially two agonist pharmacophores within the same molecule were synthesized and tested for receptor binding affinity and muscarinic agonist activity. A series of bis-1,2,5-thiadiazole derivatives of 1,2,5,6-tetrahydropyridine linked by an alkyloxy moiety exhibited very high affinity (K-i < 1 nM) and strong agonist activity. The degree of activity depended on the length of the linking alkyl group, which could be replaced by a poly(ethylene glycol) moiety, resulting in improved water solubility, binding affinity, and agonist potency.