3-(1H-Pyrazol-4-YL)phenylboronic acid | 1373043-38-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(1H-Pyrazol-4-YL)phenylboronic acid
• 英文别名: [3-(1H-pyrazol-4-yl)phenyl]boronic acid
• CAS: 1373043-38-9
• 化学式: C₉H₉BN₂O₂
• 分子量: 187.994
• InChiKey: QBDJJDPLGPHNJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.24
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-iodo-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide 、 3-(1H-Pyrazol-4-YL)phenylboronic acid 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.33h， 生成 4-((3-Methoxyphenyl)amino)-8-methyl-6-(1H-pyrazol-4-yl)quinoline-3-carboxamide (17j)
  参考文献：
  名称：

  Repurposing Human PDE4 Inhibitors for Neglected Tropical Diseases. Evaluation of Analogs of the Human PDE4 Inhibitor GSK-256066 as Inhibitors of PDEB1 ofTrypanosoma brucei

  摘要：

  Cyclic nucleotide phosphodiesterases (PDEs) have been identified as important enzyme targets for drug development in both humans and Trypanosoma brucei, the causative agent of human African trypanosomiasis. With this in mind, we recently reported the profiling of a range of human phosphodiesterase inhibitors, showing that human PDE4 inhibitors tend to display the best potency against the trypanosomal phosphodiesterase TbrPDEB1. Among these was GSK‐256066, a potent inhibitor of human PDE4 and a weak inhibitor of TbrPDEB1. In this report, we describe the results of a structure–activity relationship study of this chemotype, leading to the discovery of analogs with improved potency against TbrPDEB1 and micromolar inhibition of T. brucei cellular growth. We rationalize the potency trends via molecular docking of the new inhibitors into a recently reported apo structure of TbrPDEB1. The studies in this article will inform future efforts in repurposing human PDE inhibitors as antitrypanosomal agents.

  DOI：

  10.1111/cbdd.12443

文献信息

• Fragment-Based Approaches to the Development of <i>Mycobacterium tuberculosis</i> CYP121 Inhibitors
  作者：Madeline E. Kavanagh、Anthony G. Coyne、Kirsty J. McLean、Guy G. James、Colin W. Levy、Leonardo B. Marino、Luiz Pedro S. de Carvalho、Daniel S. H. Chan、Sean A. Hudson、Sachin Surade、David Leys、Andrew W. Munro、Chris Abell

  DOI：10.1021/acs.jmedchem.6b00007

  日期：2016.4.14

  efficiency of structural motifs to be assessed, the identification of more LE scaffolds for optimization and highlighted binding affinity hotspots. Structure-guided addition of a metal-binding pharmacophore onto LE retrofragment scaffolds produced low nanomolar (KD = 15 nM) CYP121 ligands. Elaboration of these compounds to target binding hotspots in the distal active site afforded compounds with excellent

  必需酶 CYP121 是针对结核分枝杆菌耐药菌株的药物开发的靶点。使用级联生物物理测定法鉴定出三唑-1-基苯酚片段 1 与 CYP121 结合。1 的合成合并和优化使结合亲和力提高了 100 倍，产生了先导化合物 2 (KD = 15 μM)。将 2 解构为其组件逆向片段允许评估结构基序的组效率，识别更多用于优化的 LE 支架并突出结合亲和力热点。在 LE 逆向片段支架上结构引导添加金属结合药效团产生低纳摩尔 (KD = 15 nM) CYP121 配体。将这些化合物用于靶向远端活性位点的结合热点提供了对人类药物代谢 P450 具有优异选择性的化合物。使用 X 射线晶体学、紫外-可见光谱和天然质谱分析控制配体效力和选择性的因素，为后续药物开发提供了见解。
• Pyrazine-based Syk kinase inhibitors
  作者：Pilar Forns、Cristina Esteve、Lorena Taboada、Juan Antonio Alonso、Adelina Orellana、Mónica Maldonado、Cristina Carreño、Isabel Ramis、Manel López、Montserrat Miralpeix、Bernat Vidal

  DOI：10.1016/j.bmcl.2012.02.087

  日期：2012.4

  A series of aminopyrazines as inhibitors of Syk kinase activity and showing inhibition of LAD2 cells degranulation is described. Optimization of the carboxamide motif with aminomethylpiperidines provided high potency inhibiting Syk but low cellular activity. Amides of cis and trans adamantanol showed good inhibitory activity against Syk as well as remarkable activity in LAD2 cells degranulation assay. (C) 2012 Elsevier Ltd. All rights reserved.
• Repurposing Human PDE4 Inhibitors for Neglected Tropical Diseases. Evaluation of Analogs of the Human PDE4 Inhibitor GSK-256066 as Inhibitors of PDEB1 of<i>Trypanosoma brucei</i>
  作者：Stefan O. Ochiana、Nicholas D. Bland、Luca Settimo、Robert K. Campbell、Michael P. Pollastri

  DOI：10.1111/cbdd.12443

  日期：2015.5

  Cyclic nucleotide phosphodiesterases (PDEs) have been identified as important enzyme targets for drug development in both humans and Trypanosoma brucei, the causative agent of human African trypanosomiasis. With this in mind, we recently reported the profiling of a range of human phosphodiesterase inhibitors, showing that human PDE4 inhibitors tend to display the best potency against the trypanosomal phosphodiesterase TbrPDEB1. Among these was GSK‐256066, a potent inhibitor of human PDE4 and a weak inhibitor of TbrPDEB1. In this report, we describe the results of a structure–activity relationship study of this chemotype, leading to the discovery of analogs with improved potency against TbrPDEB1 and micromolar inhibition of T. brucei cellular growth. We rationalize the potency trends via molecular docking of the new inhibitors into a recently reported apo structure of TbrPDEB1. The studies in this article will inform future efforts in repurposing human PDE inhibitors as antitrypanosomal agents.