4-{2-[(4-ethoxycarbonyl)piperidin-1-yl]ethoxy}benzenesulfonamide | 1375453-70-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-{2-[(4-ethoxycarbonyl)piperidin-1-yl]ethoxy}benzenesulfonamide
• 英文别名: Ethyl 1-[2-(4-sulfamoylphenoxy)ethyl]piperidine-4-carboxylate
• CAS: 1375453-70-5
• 化学式: C₁₆H₂₄N₂O₅S
• 分子量: 356.443
• InChiKey: SFQPIBRBXLQPHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-{2-[(4-ethoxycarbonyl)piperidin-1-yl]ethoxy}benzenesulfonamide 、 异氰酸苯酯 在 sodium hydroxide 作用下， 以 丙酮 为溶剂， 反应 4.17h， 以61%的产率得到1-phenyl-3-[4-(2-(4-ethoxycarbonylpiperidin-1-yl)ethoxy)benzene]sulfonylurea
  参考文献：
  名称：

  Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies

  摘要：

  The combination of antagonism at histamine H-3 receptor and the stimulation of insulin secretion have been proposed as an approach to new dual therapeutic agents for the treatment of type 2 diabetes mellitus associated with obesity. We have designed and synthesized a new series of non-imidazole derivatives, based on a basic amine ring connected through an alkyl spacer of variable length to a phenoxysulfonylurea moiety. These compounds were initially evaluated for histamine H-3 receptor binding affinities, suggesting that a propoxy chain linker between the amine and the core ring could be essential for optimal binding affinity. Compound 56, 1-(naphthalen-1-yl)-3-[(p-(3-pyrrolidin-1-ylpropoxy) benzene)]sulfonylurea exhibited the best H-3 antagonism affinity. However, since all these derivatives failed to block K-ATP channels, the link of these two related moieties should not be considered a good pharmacophore for obtaining new dual H-3 antagonists with insulinotropic activity, suggesting the necessity to propose a new chemical hybrid prototype. (C)2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.02.049
• 作为产物：
  描述：

  2-苯氧乙基溴 在 氯磺酸 、 氨 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 23.75h， 生成 4-{2-[(4-ethoxycarbonyl)piperidin-1-yl]ethoxy}benzenesulfonamide
  参考文献：
  名称：

  Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies

  摘要：

  The combination of antagonism at histamine H-3 receptor and the stimulation of insulin secretion have been proposed as an approach to new dual therapeutic agents for the treatment of type 2 diabetes mellitus associated with obesity. We have designed and synthesized a new series of non-imidazole derivatives, based on a basic amine ring connected through an alkyl spacer of variable length to a phenoxysulfonylurea moiety. These compounds were initially evaluated for histamine H-3 receptor binding affinities, suggesting that a propoxy chain linker between the amine and the core ring could be essential for optimal binding affinity. Compound 56, 1-(naphthalen-1-yl)-3-[(p-(3-pyrrolidin-1-ylpropoxy) benzene)]sulfonylurea exhibited the best H-3 antagonism affinity. However, since all these derivatives failed to block K-ATP channels, the link of these two related moieties should not be considered a good pharmacophore for obtaining new dual H-3 antagonists with insulinotropic activity, suggesting the necessity to propose a new chemical hybrid prototype. (C)2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.02.049

文献信息

• Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies
  作者：Javier Ceras、Nuria Cirauqui、Silvia Pérez-Silanes、Ignacio Aldana、Antonio Monge、Silvia Galiano

  DOI：10.1016/j.ejmech.2012.02.049

  日期：2012.6

  The combination of antagonism at histamine H-3 receptor and the stimulation of insulin secretion have been proposed as an approach to new dual therapeutic agents for the treatment of type 2 diabetes mellitus associated with obesity. We have designed and synthesized a new series of non-imidazole derivatives, based on a basic amine ring connected through an alkyl spacer of variable length to a phenoxysulfonylurea moiety. These compounds were initially evaluated for histamine H-3 receptor binding affinities, suggesting that a propoxy chain linker between the amine and the core ring could be essential for optimal binding affinity. Compound 56, 1-(naphthalen-1-yl)-3-[(p-(3-pyrrolidin-1-ylpropoxy) benzene)]sulfonylurea exhibited the best H-3 antagonism affinity. However, since all these derivatives failed to block K-ATP channels, the link of these two related moieties should not be considered a good pharmacophore for obtaining new dual H-3 antagonists with insulinotropic activity, suggesting the necessity to propose a new chemical hybrid prototype. (C)2012 Elsevier Masson SAS. All rights reserved.