4-[6-imino-3-(4-prop-2-ynyloxy-phenyl)-6H-pyridazin-1-yl]-butyric acid hydrobromide | 1318791-96-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-[6-imino-3-(4-prop-2-ynyloxy-phenyl)-6H-pyridazin-1-yl]-butyric acid hydrobromide
• 英文别名: 4-[6-Imino-3-(4-prop-2-ynoxyphenyl)pyridazin-1-yl]butanoic acid;hydrobromide
• CAS: 1318791-96-6
• 化学式: BrH*C₁₇H₁₇N₃O₃
• 分子量: 392.252
• InChiKey: UFFRQWGPAGNUKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  86
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(6-aminopyridazin-3-yl)phenol 在 吗啉 、 四(三苯基膦)钯 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 4-[6-imino-3-(4-prop-2-ynyloxy-phenyl)-6H-pyridazin-1-yl]-butyric acid hydrobromide
  参考文献：
  名称：

  基于 gabazine (SR-95531) 的高效 GABAA 受体拮抗剂的合成和评价

  摘要：

  描述了基于 gabazine 结构的高效类似物的选择。它们的合成仅通过四个步骤进行，并测量了它们对 GABA A受体的拮抗作用。与母体竞争性拮抗剂 gabazine 相比，所有拮抗剂都显示出显着更高的效力。

  DOI：

  10.1016/j.bmcl.2011.05.067

文献信息

• [EN] TREATING NEUROMUSCULAR OR NEUROLOGIC DISEASE THROUGH REDUCING GABAERGIC AND/OR GLYCINERGIC INHIBITORY NEUROTRANSMITTER OVERSTIMULATION<br/>[FR] TRAITEMENT DE MALADIE NEUROMUSCULAIRE OU NEUROLOGIQUE PAR RÉDUCTION DE LA SURSTIMULATION DES NEUROTRANSMETTEURS INHIBITEURS GABAERGIQUES ET/OU GLYCINERGIQUE
  申请人：RY PHARMA B V

  公开号：WO2016114655A1

  公开（公告）日：2016-07-21

  The disclosure provides novel methods of treating neuromuscular or neurologic disease, for example, Amyotrophic lateral sclerosis (ALS), through reducing GABAergic and Glycinergic inhibitory neurotransmitter activity overstimulation. Pharmaceutical compositions comprising one or more compounds capable of reducing Glycinergic activity and/or one or more compounds capable of reducing GABAergic activity are also provided. Methods for treating one or more symptoms caused by inhibitory neurotransmitter overstimulation (e.g., muscle wasting, loss of muscle function, loss of muscle coordination, respiratory depression, dysphagia, dysarthria, eye movement difficulties, oculomotor gaze palsy, supranuclear gaze palsy, bladder dysfunction and gastrointestinal dysfunction) in an individual afflicted with ALS or an ALS- like disorder are also provided.
• [EN] TREATING NEUROMUSCULAR OR NEUROLOGIC DISEASE THROUGH REDUCING GABAERGIC AND/OR GLYCINERGIC INHIBITORY NEUROTRANSMITTER OVERSTIMULATION<br/>[FR] TRAITEMENT DE MALADIE NEUROMUSCULAIRE OU NEUROLOGIQUE PAR RÉDUCTION DE LA SURSTIMULATION DES NEUROTRANSMETTEURS INHIBITEURS GABAERGIQUES ET/OU GLYCINERGIQUES
  申请人：RY PHARMA B V

  公开号：WO2017065602A1

  公开（公告）日：2017-04-20

  The disclosure provides novel methods of treating neuromuscular or neurologic disease, for example, Amyotrophic lateral sclerosis (ALS), through reducing GABAergic and Glycinergic inhibitory neurotransmitter activity overstimulation. Pharmaceutical compositions comprising one or more compounds capable of reducing Glycinergic activity and/or one or more compounds capable of reducing GABAergic activity are also provided. Pharmaceutical compositions comprising Penicillin G and, optionally, glucocorticoid are especially useful in the present invention. Methods for treating one or more symptoms caused by inhibitory neurotransmitter overstimulation (e.g., muscle wasting, loss of muscle function, loss of muscle coordination, respiratory depression, dysphagia, dysarthria, eye movement difficulties, oculomotor gaze palsy, supranuclear gaze palsy, bladder dysfunction and gastrointestinal dysfunction) in an individual afflicted with ALS or an ALS- like disorder are also provided.
• Synthesis and evaluation of highly potent GABAA receptor antagonists based on gabazine (SR-95531)
  作者：Favaad Iqbal、Ryan Ellwood、Martin Mortensen、Trevor G. Smart、James R. Baker

  DOI：10.1016/j.bmcl.2011.05.067

  日期：2011.7

  A selection of highly potent analogues based on the gabazine structure is described. Their syntheses are carried out in just four steps, and their potencies for antagonism at the GABAA receptor were measured. All antagonists showed significantly higher potencies compared to the parent competitive antagonist, gabazine.

  描述了基于 gabazine 结构的高效类似物的选择。它们的合成仅通过四个步骤进行，并测量了它们对 GABA A受体的拮抗作用。与母体竞争性拮抗剂 gabazine 相比，所有拮抗剂都显示出显着更高的效力。