4-(p-nitrophenyl)-6-methyl-3-cyano-2-pyridone | 134600-00-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(p-nitrophenyl)-6-methyl-3-cyano-2-pyridone
• 英文别名: 6-methyl-4-(4-nitrophenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile；6-methyl-4-(4-nitrophenyl)-1-oxo-1,1-dihydropyridine-3-carbonitrile；6-Methyl-4-(4-nitro-phenyl)-2-oxo-1,2-dihydro-pyridine-3-carbonitrile；6-methyl-4-(4-nitrophenyl)-2-oxo-1H-pyridine-3-carbonitrile
• CAS: 134600-00-3
• 化学式: C₁₃H₉N₃O₃
• 分子量: 255.233
• InChiKey: FDNNBHGTFULOPT-UHFFFAOYSA-N

物化性质

• 沸点：
  494.5±45.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  98.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(p-nitrophenyl)-6-methyl-3-cyano-2-pyridone 在 盐酸羟胺 、 potassium tert-butylate 、 铁粉 、 溶剂黄146 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 三氯氧磷 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 4-acrylamido-N-(4-(3-amino-6-methylisoxazolo[3,4-b]pyridin-4-yl)phenyl)-3-bromobenzamide
  参考文献：
  名称：

  4-(4-氨基苯基)-6-甲基异恶唑并[3,4-b]吡啶-3-胺共价抑制剂作为治疗急性髓系白血病的潜在药物的合成和生物学评价

  摘要：

  Fms 样酪氨酸激酶 3 (FLT3) 突变与复发风险增加密切相关，不可逆的共价 FLT3 抑制剂有可能克服耐药性。在本研究中，我们方便地合成了一系列简化的 4-(4-氨基苯基)-6-甲基异恶唑并[3,4-b] 吡啶-3-胺衍生物，其中含有两种迈克尔受体（乙烯基磺酰胺、丙烯酰胺）以靶向 FLT3及其内部串联重复 (ITD) 突变体不可逆转。激酶抑制活性表明，化合物C14在 1 μM 浓度下对 FLT3 (IC 50  = 256 nM) 和 FLT3-ITD 的抑制活性分别为 73 % 和 25.34 %。抗肿瘤活性表明C14对携带 FLT3-ITD 突变体的人急性髓性白血病 (AML) 细胞系 MOLM-13 (IC 50  = 507 nM) 以及携带 FLT3-ITD 突变体的 MV4-11 (IC 50  = 325 nM)具有强抑制活性。生化分析表明，这些作用与C14抑制FLT3

  DOI：

  10.1016/j.bmc.2022.116937
• 作为产物：
  描述：

  对硝基苯甲醛 在 potassium tert-butylate 、 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 21.0h， 生成 4-(p-nitrophenyl)-6-methyl-3-cyano-2-pyridone
  参考文献：
  名称：

  4-(4-氨基苯基)-6-甲基异恶唑并[3,4-b]吡啶-3-胺共价抑制剂作为治疗急性髓系白血病的潜在药物的合成和生物学评价

  摘要：

  Fms 样酪氨酸激酶 3 (FLT3) 突变与复发风险增加密切相关，不可逆的共价 FLT3 抑制剂有可能克服耐药性。在本研究中，我们方便地合成了一系列简化的 4-(4-氨基苯基)-6-甲基异恶唑并[3,4-b] 吡啶-3-胺衍生物，其中含有两种迈克尔受体（乙烯基磺酰胺、丙烯酰胺）以靶向 FLT3及其内部串联重复 (ITD) 突变体不可逆转。激酶抑制活性表明，化合物C14在 1 μM 浓度下对 FLT3 (IC 50  = 256 nM) 和 FLT3-ITD 的抑制活性分别为 73 % 和 25.34 %。抗肿瘤活性表明C14对携带 FLT3-ITD 突变体的人急性髓性白血病 (AML) 细胞系 MOLM-13 (IC 50  = 507 nM) 以及携带 FLT3-ITD 突变体的 MV4-11 (IC 50  = 325 nM)具有强抑制活性。生化分析表明，这些作用与C14抑制FLT3

  DOI：

  10.1016/j.bmc.2022.116937

文献信息

• Substituted aminopyrazolopyridines and salts thereof, their preparations and pharmaceutical compositions comprising them.
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP1867648A1

  公开（公告）日：2007-12-19

  The invention relates to substituted pyrazolopyridines according to the general formula (1) : in which A, B, D, E, Ra, R1, R2, R3, R4, R5 and q are as defined in the claims, and salts thereof, to pharmaceutical compositions comprising said substituted pyrazolopyridine compounds, to methods of preparing said substituted pyrazolopyridines, as well as to uses thereof for manufacturing a pharmaceutical composition for the treatment of diseases of dysregulated vascular growth or of diseases which are accompanied with dysregulated vascular growth, wherein the compounds effectively interfere with Tie2 signaling.

  该发明涉及根据通式（1）所示的取代吡唑吡啶化合物：其中A、B、D、E、Ra、R1、R2、R3、R4、R5和q如权利要求中所定义的，以及其盐，包括所述取代吡唑吡啶化合物的药物组合物，制备所述取代吡唑吡啶的方法，以及用于制造用于治疗血管生长失调疾病或伴随血管生长失调的疾病的药物组合物的用途，其中这些化合物有效干扰Tie2信号传导。
• SUBSTITUTED PYRAZOLOPYRIDINES AND SALTS THEREOF, PHARMACEUTICAL COMPOSITIONS COMPRISING SAME, METHODS OF PREPARING SAME AND USES OF SAME
  申请人：Hartung Ingo

  公开号：US20080058326A1

  公开（公告）日：2008-03-06

  The invention relates to substituted pyrazolopyridines according to the general formula (I): in which A, B, D, E, R a , R 1 , R 2 , R 3 , R 4 , R 5 and q are as defined in the claims, and salts thereof, to pharmaceutical compositions comprising said substituted pyrazolopyridine compounds, to methods of preparing said substituted pyrazolopyridines, as well as to uses thereof for manufacturing a pharmaceutical composition for the treatment of diseases of dysregulated vascular growth or of diseases which are accompanied with dysregulated vascular growth, wherein the compounds effectively interfere with Tie2 signalling.

  本发明涉及一般式（I）的取代吡唑吡啶化合物，其中A、B、D、E、Ra、R1、R2、R3、R4、R5和q如权利要求所定义，并且其盐，以及包括所述取代吡唑吡啶化合物的制药组合物，制备所述取代吡唑吡啶化合物的方法，以及将其用于制造治疗失调血管生长疾病或伴随失调血管生长的疾病的制药组合物的用途，其中这些化合物有效地干扰Tie2信号传导。
• SUBSTITUTED ARYLPYRAZOLOPYRIDINES AND SALTS THEREOF, PHARMACEUTICAL COMPOSITIONS COMPRISING SAME, METHODS OF PREPARING SAME AND USES OF SAME
  申请人：Hartung Ingo

  公开号：US20080064707A1

  公开（公告）日：2008-03-13

  The invention relates to substituted arylpyrazolopyridines according to the general formula (I): in which A, B, D, E, R a , R 1 , R 2 , R 3 , R 4 , R 5 and q are as defined in the claims, and salts thereof, to pharmaceutical compositions comprising said substituted arylpyrazolopyridines, to methods of preparing said substituted arylpyrazolopyridines as well as the use thereof for manufacturing a pharmaceutical composition for the treatment of diseases of dysregulated vascular growth or of diseases which are accompanied with dysregulated vascular growth, wherein the compounds effectively interfere with Tie2 signalling.

  本发明涉及一种按照通式(I)所示的取代芳基吡唑吡啶化合物，其中A、B、D、E、Ra、R1、R2、R3、R4、R5和q的定义如权利要求书中所述，以及其盐。本发明还涉及包含所述取代芳基吡唑吡啶化合物的药物组合物，制备所述取代芳基吡唑吡啶化合物的方法以及其用于制造用于治疗失调的血管生长或伴随失调的血管生长疾病的药物组合物的用途，其中该化合物有效地干扰Tie2信号传导。
• Substituted pyrazolopyridines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same
  申请人：Bayer Schering Pharma AG

  公开号：US07846928B2

  公开（公告）日：2010-12-07

  The invention relates to substituted pyrazolopyridines according to the general formula (I): in which A, B, D, E, Ra, R1, R2, R3, R4, R5 and q are as defined in the claims, and salts thereof, to pharmaceutical compositions comprising said substituted pyrazolopyridine compounds, to methods of preparing said substituted pyrazolopyridines, as well as to uses thereof for manufacturing a pharmaceutical composition for the treatment of diseases of dysregulated vascular growth or of diseases which are accompanied with dysregulated vascular growth, wherein the compounds effectively interfere with Tie2 signalling.

  本发明涉及一般式（I）的取代吡唑吡啶，其中A、B、D、E、Ra、R1、R2、R3、R4、R5和q如权利要求书所定义，以及其盐，包括所述取代吡唑吡啶化合物的制药组合物，制备所述取代吡唑吡啶的方法，以及将其用于制造用于治疗失调血管生长疾病或伴随失调血管生长的疾病的制药组合物的用途，其中该化合物有效干扰Tie2信号。
• Substituted arylpyrazolopyridines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same
  申请人：Bayer Schering Pharma AG

  公开号：US07795264B2

  公开（公告）日：2010-09-14

  The invention relates to substituted arylpyrazolopyridines according to the general formula (I): in which A, B, D, E, Ra, R1, R2, R3, R4, R5 and q are as defined in the claims, and salts thereof, to pharmaceutical compositions comprising said substituted arylpyrazolopyridines, to methods of preparing said substituted arylpyrazolopyridines as well as the use thereof for manufacturing a pharmaceutical composition for the treatment of diseases of dysregulated vascular growth or of diseases which are accompanied with dysregulated vascular growth, wherein the compounds effectively interfere with Tie2 signalling.

  本发明涉及一种通式（I）所示的取代芳基吡唑吡啶化合物，其中A、B、D、E、Ra、R1、R2、R3、R4、R5和q如权利要求书所定义，以及其盐，制备该取代芳基吡唑吡啶化合物的方法，以及将其用于制备治疗失调血管生长或伴随失调血管生长的疾病的药物组合物的用途，其中该化合物有效地干扰Tie2信号传导。