6,7-dihydro-3-methyl-6-oxo-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile | 52217-38-6

• 物质功能分类: 医药中间体 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6,7-dihydro-3-methyl-6-oxo-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile
• 英文别名: 3-Methyl-6-oxo-1-phenyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile；3-methyl-6-oxo-1-phenyl-7H-pyrazolo[3,4-b]pyridine-5-carbonitrile
• CAS: 52217-38-6
• 化学式: C₁₄H₁₀N₄O
• 分子量: 250.26
• InChiKey: ZLQQCJLXBVVVMR-UHFFFAOYSA-N

物化性质

• 熔点：
  306-308 °C(Solv: acetic acid (64-19-7))
• 沸点：
  504.8±50.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  70.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6,7-dihydro-3-methyl-6-oxo-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile 在 palladium on activated charcoal 、 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 3-methyl-5-((methyl(3-(trifluoromethyl)benzyl)amino)methyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one
  参考文献：
  名称：

  Discovery of Pyrazolopyridones as a Novel Class of Noncovalent DprE1 Inhibitor with Potent Anti-Mycobacterial Activity

  摘要：

  A novel pyrazolopyridone class of inhibitors was identified from whole cell screening against Mycobacterium tuberculosis (Mtb). The series exhibits excellent bactericidality in vitro, resulting in a 4 log reduction in colony forming units following compound exposure. The significant modulation of minimum inhibitory concentration (MIC) against a Mtb strain overexpressing the Rv3790 gene suggested the target of pyrazolopyridones to be decaprenylphosphoryl-beta-D-ribose-2'-epimerase (DprE1). Genetic mapping of resistance mutation coupled with potent enzyme inhibition activity confirmed the molecular target. Detailed biochemical characterization revealed the series to be a noncovalent inhibitor of DprE1. Docking studies at the active site suggest that the series can be further diversified to improve the physicochemical properties without compromising the antimycobacterial activity. The pyrazolopyridone class of inhibitors offers an attractive non-nitro lead series targeting the essential and vulnerable DprE1 enzyme for the discovery of novel antimycobacterial agents to treat both drug susceptible and drug resistant strains of Mtb.

  DOI：

  10.1021/jm5002937
• 作为产物：
  描述：

  依达拉奉 在 sodium azide 、 sodium dithionite 、 四丁基硫酸氢铵 、 三氯氧磷 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 生成 6,7-dihydro-3-methyl-6-oxo-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile
  参考文献：
  名称：

  Discovery of Pyrazolopyridones as a Novel Class of Noncovalent DprE1 Inhibitor with Potent Anti-Mycobacterial Activity

  摘要：

  A novel pyrazolopyridone class of inhibitors was identified from whole cell screening against Mycobacterium tuberculosis (Mtb). The series exhibits excellent bactericidality in vitro, resulting in a 4 log reduction in colony forming units following compound exposure. The significant modulation of minimum inhibitory concentration (MIC) against a Mtb strain overexpressing the Rv3790 gene suggested the target of pyrazolopyridones to be decaprenylphosphoryl-beta-D-ribose-2'-epimerase (DprE1). Genetic mapping of resistance mutation coupled with potent enzyme inhibition activity confirmed the molecular target. Detailed biochemical characterization revealed the series to be a noncovalent inhibitor of DprE1. Docking studies at the active site suggest that the series can be further diversified to improve the physicochemical properties without compromising the antimycobacterial activity. The pyrazolopyridone class of inhibitors offers an attractive non-nitro lead series targeting the essential and vulnerable DprE1 enzyme for the discovery of novel antimycobacterial agents to treat both drug susceptible and drug resistant strains of Mtb.

  DOI：

  10.1021/jm5002937

文献信息

• Synthesis of Newly Substituted Pyrazoles and Substituted Pyrazolo[3,4-<i>b</i>]Pyridines Based on 5-Amino-3-Methyl-1-Phenylpyrazole
  作者：Talaat I. El-Emary

  DOI：10.1002/jccs.200700072

  日期：2007.4

  10b was produced through reaction of 9 with acetophenone. Reaction of 1 with benzylidinemalononitrile afforded 11. New methods for preparation of 15 and 16 are described. The reaction of 8 with malononitrile, thio-semicarbazide, phenyl hydrazine and acetophenone afforded compounds 18-21. The reaction of 21 with malononitrile gave 22. Compounds 23-26 were produced upon reaction of 10a with malononitrile

  氨基吡唑1与苯磺酰氯、芳烃重氮盐、氯乙酰氯、乙氧基亚甲基亚甲基腈和2-氰基-3-乙氧基丙烯酸乙酯反应得到取代的3-甲基-1-苯基吡唑2-5a、b。通过分别用AlCl 3 和POCl 3 处理化合物5b，将其环化为6和7。化合物 6 通过在 POCl 3 /PCl 5 中煮沸转化为 7。化合物10b由9与苯乙酮反应生成。1 与苄基丙二腈反应得到 11。描述了制备 15 和 16 的新方法。8与丙二腈、硫代氨基脲、苯肼和苯乙酮反应得到化合物18-21。21 与丙二腈反应得到 22。化合物 23-26 在 10a 与丙二腈、苯肼、氨基硫脲、
• El-Emary; Hussein; El-Kashef, Pharmazie, 2000, vol. 55, # 5, p. 356 - 358
  作者：El-Emary、Hussein、El-Kashef

  DOI：——

  日期：——
• Discovery of Novel Pyrazolo[3,4-<i>b</i>] Pyridine Derivatives with Dual Activities of Vascular Remodeling Inhibition and Vasodilation for the Treatment of Pulmonary Arterial Hypertension
  作者：Liqing Hu、Lijun Li、Qi Chang、Songsen Fu、Jia Qin、Zhuo Chen、Xiaohui Li、Qinglian Liu、Gaoyun Hu、Qianbin Li

  DOI：10.1021/acs.jmedchem.0c01132

  日期：2020.10.8

  Current pulmonary arterial hypertension (PAH) therapeutic strategies mainly focus on vascular relaxation with less emphasis on vascular remodeling, which results in poor prognosis. Hence, dual pathway regulators with vasodilation effect via soluble guanylate cyclase (sGC) stimulation and vascular remodeling regulation effect by AMP-activated protein kinase (AMPK) inhibition provide more advantages and potentialities. Herein, we designed and synthesized a series of novel pyrazolo[3,4-b] pyridine derivatives based on sGC stimulator and AMPK inhibitor scaffolds. In vitro, 2 exhibited moderate vasodilation activity and higher proliferation and migration suppressive effects compared to riociguat. In vivo, 2 significantly decreased right ventricular systolic pressure (RVSP), attenuated pulmonary artery medial thickness (PAMT), and right ventricular hypertrophy (RVH) in hypoxia-induced PAH rat models (i.g.). Given the unique advantages of significant vascular remodeling inhibition and moderate vascular relaxation based on the dual pathway regulation, we proposed 2 as a promising lead for anti-PAH drug discovery.
• Simay, A.; Takacs, K.; Toth, L., Acta Chimica Academiae Scientiarum Hungaricae, 1982, vol. 109, # 2, p. 175 - 188
  作者：Simay, A.、Takacs, K.、Toth, L.

  DOI：——

  日期：——
• El-Latif, Fawi M. Abd, Journal of the Indian Chemical Society, 1994, vol. 71, # 10, p. 631 - 634
  作者：El-Latif, Fawi M. Abd

  DOI：——

  日期：——