6-chloro-2-(2-fluoro-phenyl)oxazolo<5,4-b>pyridine | 126921-80-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-chloro-2-(2-fluoro-phenyl)oxazolo<5,4-b>pyridine
• 英文别名: 5-chloro-2-(2-fluorophenyl)oxazolo[5,4-b]pyridine；5-chloro-2-(2-fluorophenyl)oxazolo[ 5,4-b]pyridine；5-chloro-2-(2-fluorophenyl)-[1,3]oxazolo[5,4-b]pyridine
• CAS: 126921-80-0
• 化学式: C₁₂H₆ClFN₂O
• 分子量: 248.644
• InChiKey: IOKSCCZABWKVOW-UHFFFAOYSA-N

物化性质

• 沸点：
  336.4±32.0 °C(Predicted)
• 密度：
  1.427±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  哌啶 、 6-chloro-2-(2-fluoro-phenyl)oxazolo<5,4-b>pyridine 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以9%的产率得到2-(2-fluorophenyl)-5-(piperidin-1-yl)oxazolo[5,4-b]pyridine
  参考文献：
  名称：

  Oxazolopyridines and thiazolopyridines as monoamine oxidase B inhibitors for the treatment of Parkinson’s disease

  摘要：

  In Parkinson's disease, the motor impairments are mainly caused by the death of dopaminergic neurons. Among the enzymes which are involved in the biosynthesis and catabolism of dopamine, monoamine oxidase B (MAO-B) has been a therapeutic target of Parkinson's disease. However, due to the undesirable adverse effects, development of alternative MAO-B inhibitors with greater optimal therapeutic potential towards Parkinson's disease is urgently required. In this study, we designed and synthesized the oxazolopyridine and thiazolopyridine derivatives, and biologically evaluated their inhibitory activities against MAO-B. Structure-activity relationship study revealed that the piperidino group was the best choice for the R-1 amino substituent to the oxazolopyridine core structure and the activities of the oxazolopyridines with various phenyl rings were between 267.1 and 889.5 nM in IC50 values. Interestingly, by replacement of the core structure from oxazolopyrine to thiazolopyridine, the activities were significantly improved and the compound in with the thiazolopyridine core structure showed the most potent activity with the IC50 value of 26.5 nM. Molecular docking study showed that van der Waals interaction in the human MAO-B active site could explain the enhanced inhibitory activities of thiazolopyridine derivatives. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.066
• 作为产物：
  描述：

  2,6-二氯-3-氨基吡啶 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 30.0h， 生成 6-chloro-2-(2-fluoro-phenyl)oxazolo<5,4-b>pyridine
  参考文献：
  名称：

  Oxazolopyridines and thiazolopyridines as monoamine oxidase B inhibitors for the treatment of Parkinson’s disease

  摘要：

  In Parkinson's disease, the motor impairments are mainly caused by the death of dopaminergic neurons. Among the enzymes which are involved in the biosynthesis and catabolism of dopamine, monoamine oxidase B (MAO-B) has been a therapeutic target of Parkinson's disease. However, due to the undesirable adverse effects, development of alternative MAO-B inhibitors with greater optimal therapeutic potential towards Parkinson's disease is urgently required. In this study, we designed and synthesized the oxazolopyridine and thiazolopyridine derivatives, and biologically evaluated their inhibitory activities against MAO-B. Structure-activity relationship study revealed that the piperidino group was the best choice for the R-1 amino substituent to the oxazolopyridine core structure and the activities of the oxazolopyridines with various phenyl rings were between 267.1 and 889.5 nM in IC50 values. Interestingly, by replacement of the core structure from oxazolopyrine to thiazolopyridine, the activities were significantly improved and the compound in with the thiazolopyridine core structure showed the most potent activity with the IC50 value of 26.5 nM. Molecular docking study showed that van der Waals interaction in the human MAO-B active site could explain the enhanced inhibitory activities of thiazolopyridine derivatives. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.066

文献信息

• Flouzant, Christine; Guillaumet, Gerald, Synthesis, 1990, # 1, p. 64 - 66
  作者：Flouzant, Christine、Guillaumet, Gerald

  DOI：——

  日期：——
• US4038396A
  申请人：——

  公开号：US4038396A

  公开（公告）日：1977-07-26
• US4131677A
  申请人：——

  公开号：US4131677A

  公开（公告）日：1978-12-26
• Oxazolopyridines and thiazolopyridines as monoamine oxidase B inhibitors for the treatment of Parkinson’s disease
  作者：Hye Ri Park、Jiyoon Kim、Taekeun Kim、Seonmi Jo、Miyoung Yeom、Bongjin Moon、Il Han Choo、Jaeick Lee、Eun Jeong Lim、Ki Duk Park、Sun-Joon Min、Ghilsoo Nam、Gyochang Keum、C. Justin Lee、Hyunah Choo

  DOI：10.1016/j.bmc.2013.05.066

  日期：2013.9

  In Parkinson's disease, the motor impairments are mainly caused by the death of dopaminergic neurons. Among the enzymes which are involved in the biosynthesis and catabolism of dopamine, monoamine oxidase B (MAO-B) has been a therapeutic target of Parkinson's disease. However, due to the undesirable adverse effects, development of alternative MAO-B inhibitors with greater optimal therapeutic potential towards Parkinson's disease is urgently required. In this study, we designed and synthesized the oxazolopyridine and thiazolopyridine derivatives, and biologically evaluated their inhibitory activities against MAO-B. Structure-activity relationship study revealed that the piperidino group was the best choice for the R-1 amino substituent to the oxazolopyridine core structure and the activities of the oxazolopyridines with various phenyl rings were between 267.1 and 889.5 nM in IC50 values. Interestingly, by replacement of the core structure from oxazolopyrine to thiazolopyridine, the activities were significantly improved and the compound in with the thiazolopyridine core structure showed the most potent activity with the IC50 value of 26.5 nM. Molecular docking study showed that van der Waals interaction in the human MAO-B active site could explain the enhanced inhibitory activities of thiazolopyridine derivatives. (C) 2013 Elsevier Ltd. All rights reserved.