4-(3-morpholinopropoxy)benzenesulfonamide | 189334-44-9

• 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-(3-morpholinopropoxy)benzenesulfonamide
• 英文别名: 4-(3-morpholin-4-ylpropoxy)benzenesulfonamide
• CAS: 189334-44-9
• 化学式: C₁₃H₂₀N₂O₄S
• 分子量: 300.379
• InChiKey: WZPPGAGAZOALBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  90.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-苯氧基丁基溴 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-(3-morpholinopropoxy)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 Pitolisant-Derived Sulfonyl Compounds for Alzheimer Disease
  作者：Silvia Pérez-Silanes、Eva Martisova、Esther Moreno、Maite Solas、Daniel Plano、Carmen Sanmartin、María Javier Ramírez

  DOI：10.3390/ijms25020799

  日期：——

  on H3R, showed a moderate ability to inhibit acetylcholinesterase activity in vitro, and two of the compounds (derivatives 2 and 7) were also capable of increasing acetylcholine release in vitro. Among the tested compounds, derivative 2 was identified and selected for further in vivo studies. Compound 2 was able to reverse scopolamine-induced cognitive deficits with results comparable to those of galantamine

  阿尔茨海默病 （AD） 是一种复杂的多因素神经退行性疾病，其特征是认知能力下降、记忆力减退、行为改变和其他神经系统症状。考虑到对新 AD 疗法的迫切需求，在本研究中，我们设计、合成和评估了受磺脲类药物和 pitolisant 结构启发的多靶点化合物，目的是获得用于 AD 治疗的多靶点配体。由于化学支架的多样性，通过将显示 H3R 拮抗作用和乙酰胆碱酯酶抑制作用的结构部分合并成一个结构部分，采用了一种新的策略。根据它们对 H3R 的结合活性选择的 8 种化合物在体外显示出中等抑制乙酰胆碱酯酶活性的能力，其中两种化合物（衍生物 2 和 7）也能够在体外增加乙酰胆碱的释放。在测试的化合物中，鉴定并选择衍生物 2 进行进一步的体内研究。化合物 2 能够逆转东莨菪碱诱导的认知缺陷，其结果与临床用于治疗 AD 的药物加兰他敏的结果相当。除了疗效外，该化合物在体外还表现出适度的 BBB 渗透性。总而言之，这些结果表明，化合物