5-Chloro-2-(2-hydroxy-1-naphthalen-1-ylethyl)-4-(4-methoxyphenoxy)pyridazin-3-one | 1421365-51-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-Chloro-2-(2-hydroxy-1-naphthalen-1-ylethyl)-4-(4-methoxyphenoxy)pyridazin-3-one
• CAS: 1421365-51-6
• 化学式: C₂₃H₁₉ClN₂O₄
• 分子量: 422.868
• InChiKey: RUHUMVNQBCYKJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  71.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-Chloro-2-(2-hydroxy-1-naphthalen-1-ylethyl)-4-(4-methoxyphenoxy)pyridazin-3-one 、 乙酰氯 在 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以95%的产率得到[2-[4-Chloro-5-(4-methoxyphenoxy)-6-oxopyridazin-1-yl]-2-naphthalen-1-ylethyl] acetate
  参考文献：
  名称：

  SAR analysis of novel non-peptidic NPBWR1 (GPR7) antagonists

  摘要：

  In this Letter we report on the advances in our NPBWR1 antagonist program aimed at optimizing the 5-chloro-2-(3,5-dimethylphenyl)-4-(4-methoxyphenoxy)pyridazin-3(2H)-one lead molecule previously obtained from a high-throughput screening (HTS)-derived hit. Synthesis and structure-activity relationships (SAR) studies around the 3,5-dimethylphenyl and 4-methoxyphenyl regions resulted in the identification of a novel series of non-peptidic submicromolar NPBWR1 antagonists based on a 5-chloro-4-(4-alkoxyphenoxy)-2-(benzyl)pyridazin-3(2H)-one chemotype. Amongst them, 5-chloro-2-(9H-fluoren-9-yl)-4-(4-methoxyphenoxy)pyridazin-3(2H)-one 9h (CYM50769) inhibited NPW activation of NPBWR1 with a submicromolar IC50, and displayed high selectivity against a broad array of off-targets with pharmaceutical relevance. Our medicinal chemistry study provides innovative non-peptidic selective NPBWR1 antagonists that may enable to clarify the biological role and therapeutic utility of the target receptor in the regulation of feeding behavior, pain, stress, and neuroendocrine function. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.030
• 作为产物：
  描述：

  4-chloro-5-(4-methoxyphenoxy)-1H-pyridazin-6-one 在 锂硼氢 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 5-Chloro-2-(2-hydroxy-1-naphthalen-1-ylethyl)-4-(4-methoxyphenoxy)pyridazin-3-one
  参考文献：
  名称：

  SAR analysis of novel non-peptidic NPBWR1 (GPR7) antagonists

  摘要：

  In this Letter we report on the advances in our NPBWR1 antagonist program aimed at optimizing the 5-chloro-2-(3,5-dimethylphenyl)-4-(4-methoxyphenoxy)pyridazin-3(2H)-one lead molecule previously obtained from a high-throughput screening (HTS)-derived hit. Synthesis and structure-activity relationships (SAR) studies around the 3,5-dimethylphenyl and 4-methoxyphenyl regions resulted in the identification of a novel series of non-peptidic submicromolar NPBWR1 antagonists based on a 5-chloro-4-(4-alkoxyphenoxy)-2-(benzyl)pyridazin-3(2H)-one chemotype. Amongst them, 5-chloro-2-(9H-fluoren-9-yl)-4-(4-methoxyphenoxy)pyridazin-3(2H)-one 9h (CYM50769) inhibited NPW activation of NPBWR1 with a submicromolar IC50, and displayed high selectivity against a broad array of off-targets with pharmaceutical relevance. Our medicinal chemistry study provides innovative non-peptidic selective NPBWR1 antagonists that may enable to clarify the biological role and therapeutic utility of the target receptor in the regulation of feeding behavior, pain, stress, and neuroendocrine function. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.030