N-methyl-N-(4-methyl-1,3-thiazol-2-yl)-2-(6-phenylpyridazin-3-yl)sulfanylbutanamide | 1391736-91-6

• 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: N-methyl-N-(4-methyl-1,3-thiazol-2-yl)-2-(6-phenylpyridazin-3-yl)sulfanylbutanamide
• CAS: 1391736-91-6
• 化学式: C₁₉H₂₀N₄OS₂
• 分子量: 384.526
• InChiKey: PIRGLDZWHLDHMU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  113
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-氯-6-苯基哒嗪 在 caesium carbonate 、 硫脲 作用下， 以 乙腈 为溶剂， 反应 18.25h， 生成 N-methyl-N-(4-methyl-1,3-thiazol-2-yl)-2-(6-phenylpyridazin-3-yl)sulfanylbutanamide
  参考文献：
  名称：

  Further optimization of the K-Cl cotransporter KCC2 antagonist ML077: Development of a highly selective and more potent in vitro probe

  摘要：

  Further chemical optimization of the MLSCN/MLPCN probe ML077 (KCC2 IC50 = 537 nM) proved to be challenging as the effort was characterized by steep SAR. However, a multi-dimensional iterative parallel synthesis approach proved productive. Herein we report the discovery and SAR of an improved novel antagonist (VU0463271) of the neuronal-specific potassium-chloride cotransporter 2 (KCC2), with an IC50 of 61 nM and > 100-fold selectivity versus the closely related Na-K-2Cl cotransporter 1 (NKCC1) and no activity in a larger panel of GPCRs, ion channels and transporters. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.126

文献信息

• Further optimization of the K-Cl cotransporter KCC2 antagonist ML077: Development of a highly selective and more potent in vitro probe
  作者：Eric Delpire、Aleksandra Baranczak、Alex G. Waterson、Kwangho Kim、Nathan Kett、Ryan D. Morrison、J. Scott Daniels、C. David Weaver、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2012.05.126

  日期：2012.7

  Further chemical optimization of the MLSCN/MLPCN probe ML077 (KCC2 IC50 = 537 nM) proved to be challenging as the effort was characterized by steep SAR. However, a multi-dimensional iterative parallel synthesis approach proved productive. Herein we report the discovery and SAR of an improved novel antagonist (VU0463271) of the neuronal-specific potassium-chloride cotransporter 2 (KCC2), with an IC50 of 61 nM and > 100-fold selectivity versus the closely related Na-K-2Cl cotransporter 1 (NKCC1) and no activity in a larger panel of GPCRs, ion channels and transporters. (C) 2012 Elsevier Ltd. All rights reserved.