N,N-di-n-propyl-[2-(6-chloro-2-(4-hydroxyphenyl)imidazo[1,2-a]pyridin-3-yl)]acetamide | 1402402-89-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N,N-di-n-propyl-[2-(6-chloro-2-(4-hydroxyphenyl)imidazo[1,2-a]pyridin-3-yl)]acetamide
• 英文别名: 2-[6-chloro-2-(4-hydroxyphenyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dipropylacetamide
• CAS: 1402402-89-4
• 化学式: C₂₁H₂₄ClN₃O₂
• 分子量: 385.893
• InChiKey: YAYRZKKNXOKHBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.55
• 重原子数：
  27.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.84
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N,N-di-n-propyl-[2-(6-chloro-2-(4-hydroxyphenyl)imidazo[1,2-a]pyridin-3-yl)]acetamide 在 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 4-(6-chloro-3-(2-(dipropylamino)-2-oxoethyl)imidazo[1,2-a]pyridin-2-yl)phenyl-3,4-dihydroxyphenethylcarbamate
  参考文献：
  名称：

  Novel codrugs with GABAergic activity for dopamine delivery in the brain

  摘要：

  This study investigates the use of codrugs of the GABAergic agent 2-phenyl-imidazo[1,2-a]pyridinacetamide and dopamine (DA) or ethyl ester L-Dopa (LD) as a strategy to deliver DA and simultaneously activate GABA-receptors in the brain. For this purpose, both DA and LD ethyl ester were linked by carbamate bond to imidazo[1,2-a]pyridine acetamide moieties to yield two DA- and two LD-imidazopyridine derivatives. These compounds were evaluated in vitro to assess their stability, binding affinities and cell membrane transport, and in vivo to assess their bio-availability via microdialysis studies. The two DA derivatives were adequately stable in buffered solution, but underwent cleavage in diluted human serum. By contrast, the LD derivatives were unstable in buffered solution. Receptor binding studies showed that the DA-imidazopyridine carbamates had binding affinity for benzodiazepine receptors in the nanomolar range. Brain microdialysis experiments indicated that intraperitoneal administration of the DA derivatives sustained DA levels in rat striatum over a 4-h period.These results suggest that DA-imidazopyridine carbamates are new DA codrugs with potential application for DA replacement therapy. (C) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ijpharm.2012.08.023
• 作为产物：
  描述：

  4-(6-chloro-3-(2-(dipropylamino)-2-oxoethyl)imidazo[1,2-a]pyridin-2-yl)phenyl 4-nitrophenyl carbonate 在 甲醇 作用下， 以 四氢呋喃 、 aq. phosphate buffer 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 N,N-di-n-propyl-[2-(6-chloro-2-(4-hydroxyphenyl)imidazo[1,2-a]pyridin-3-yl)]acetamide
  参考文献：
  名称：

  Novel codrugs with GABAergic activity for dopamine delivery in the brain

  摘要：

  This study investigates the use of codrugs of the GABAergic agent 2-phenyl-imidazo[1,2-a]pyridinacetamide and dopamine (DA) or ethyl ester L-Dopa (LD) as a strategy to deliver DA and simultaneously activate GABA-receptors in the brain. For this purpose, both DA and LD ethyl ester were linked by carbamate bond to imidazo[1,2-a]pyridine acetamide moieties to yield two DA- and two LD-imidazopyridine derivatives. These compounds were evaluated in vitro to assess their stability, binding affinities and cell membrane transport, and in vivo to assess their bio-availability via microdialysis studies. The two DA derivatives were adequately stable in buffered solution, but underwent cleavage in diluted human serum. By contrast, the LD derivatives were unstable in buffered solution. Receptor binding studies showed that the DA-imidazopyridine carbamates had binding affinity for benzodiazepine receptors in the nanomolar range. Brain microdialysis experiments indicated that intraperitoneal administration of the DA derivatives sustained DA levels in rat striatum over a 4-h period.These results suggest that DA-imidazopyridine carbamates are new DA codrugs with potential application for DA replacement therapy. (C) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ijpharm.2012.08.023