Pyridazinone, 2-44 | 1155571-43-9

• 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: Pyridazinone, 2-44
• 英文别名: 2-(3-bromophenyl)-4,5-dichloropyridazin-3-one
• CAS: 1155571-43-9
• 化学式: C₁₀H₅BrCl₂N₂O
• 分子量: 319.972
• InChiKey: UUXKNOBHNPKNBS-UHFFFAOYSA-N

物化性质

• 熔点：
  194 °C
• 沸点：
  369.1±52.0 °C(predicted)
• 密度：
  1.77±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Pyridazinone, 2-44 、 4-甲氧基苯酚 在 sodium hydride 作用下， 以 1,4-二氧六环 为溶剂， 生成 2-(3-Bromophenyl)-5-chloro-4-(4-methoxyphenoxy)pyridazin-3-one
  参考文献：
  名称：

  Design, synthesis and SAR analysis of novel potent and selective small molecule antagonists of NPBWR1 (GPR7)

  摘要：

  Novel smallmolecule antagonists ofNPBWR1 (GPR7) are herein reported. A high-throughput screening (HTS) of the Molecular Libraries-Small Molecule Repository library identified 5-chloro-4-(4-methoxyphenoxy)-2-(p-tolyl)pyridazin-3(2H)-one as a NPBWR1 hit antagonist with micromolar activity. Design, synthesis and structure-activity relationships study of the HTS-derived hit led to the identification of 5-chloro-2-(3,5-dimethylphenyl)-4-(4-methoxyphenoxy) pyridazin-3(2H)-one lead molecule with sub-micromolar antagonist activity at the target receptor and high selectivity against a panel of therapeutically relevant off-target proteins. This lead molecule may provide a pharmacological tool to clarify the molecular basis of the in vivo physiological function and therapeutic utility of NPBWR1 in diverse disease areas including inflammatory pain and eating disorders. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.074
• 作为产物：
  描述：

  3,4-二氯-5-羟基-5H-呋喃-2-酮 、 3-溴苯肼 在 盐酸 、 水 作用下， 反应 3.0h， 生成 Pyridazinone, 2-44
  参考文献：
  名称：

  Discovery and structure–activity relationship analysis of Staphylococcus aureus sortase A inhibitors

  摘要：

  Methicillin resistant Staphylococcus aureus (MRSA) is a major health problem that has created a pressing need for new antibiotics. Compounds that inhibit the S. aureus SrtA sortase may function as potent anti-infective agents as this enzyme attaches virulence factors to the cell wall. Using high-throughput screening, we have identified several compounds that inhibit the enzymatic activity of the SrtA. A structure-activity relationship (SAR) analysis led to the identification of several pyridazinone and pyrazolethione analogs that inhibit SrtA with IC50 values in the sub-micromolar range. Many of these molecules also inhibit the sortase enzyme from Bacillus anthracis suggesting that they may be generalized sortase inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.067

文献信息

• Late-stage diversification of biologically active pyridazinones via a direct C–H functionalization strategy
  作者：Wei Li、Zhoulong Fan、Kaijun Geng、Youjun Xu、Ao Zhang

  DOI：10.1039/c4ob02061h

  日期：——

  Divergent C–H functionalization reactions (arylation, carboxylation, olefination, thiolation, acetoxylation, halogenation, naphthylation) using a pyridazinone moiety as an internal directing group were successfully established. This approach offers a late-stage, ortho-selective diversification of a biologically active pyridazinone scaffold. Seven series of novel pyridazinone analogues were synthesized

  成功建立了使用哒嗪酮部分作为内部导向基团的不同的CH功能化反应（芳基化，羧化，烯化，硫醇化，乙酰氧基化，卤化，萘化）。该方法提供了具有生物活性的哒嗪酮支架的晚期，邻位选择性多样化。方便地合成了七个系列的新型哒嗪酮类似物，作为潜在分选酶A（SrtA）抑制剂的合成前体。
• Discovery and structure–activity relationship analysis of Staphylococcus aureus sortase A inhibitors
  作者：Nuttee Suree、Sung Wook Yi、William Thieu、Melanie Marohn、Robert Damoiseaux、Albert Chan、Michael E. Jung、Robert T. Clubb

  DOI：10.1016/j.bmc.2009.08.067

  日期：2009.10

  Methicillin resistant Staphylococcus aureus (MRSA) is a major health problem that has created a pressing need for new antibiotics. Compounds that inhibit the S. aureus SrtA sortase may function as potent anti-infective agents as this enzyme attaches virulence factors to the cell wall. Using high-throughput screening, we have identified several compounds that inhibit the enzymatic activity of the SrtA. A structure-activity relationship (SAR) analysis led to the identification of several pyridazinone and pyrazolethione analogs that inhibit SrtA with IC50 values in the sub-micromolar range. Many of these molecules also inhibit the sortase enzyme from Bacillus anthracis suggesting that they may be generalized sortase inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.
• Design, synthesis and SAR analysis of novel potent and selective small molecule antagonists of NPBWR1 (GPR7)
  作者：Mariangela Urbano、Miguel Guerrero、Jian Zhao、Subash Velaparthi、S. Adrian Saldanha、Peter Chase、Zhiwei Wang、Olivier Civelli、Peter Hodder、Marie-Therese Schaeffer、Steven Brown、Hugh Rosen、Edward Roberts

  DOI：10.1016/j.bmcl.2012.09.074

  日期：2012.12

  Novel smallmolecule antagonists ofNPBWR1 (GPR7) are herein reported. A high-throughput screening (HTS) of the Molecular Libraries-Small Molecule Repository library identified 5-chloro-4-(4-methoxyphenoxy)-2-(p-tolyl)pyridazin-3(2H)-one as a NPBWR1 hit antagonist with micromolar activity. Design, synthesis and structure-activity relationships study of the HTS-derived hit led to the identification of 5-chloro-2-(3,5-dimethylphenyl)-4-(4-methoxyphenoxy) pyridazin-3(2H)-one lead molecule with sub-micromolar antagonist activity at the target receptor and high selectivity against a panel of therapeutically relevant off-target proteins. This lead molecule may provide a pharmacological tool to clarify the molecular basis of the in vivo physiological function and therapeutic utility of NPBWR1 in diverse disease areas including inflammatory pain and eating disorders. (C) 2012 Elsevier Ltd. All rights reserved.