4-((pyridin-3-ylmethyl)carbamoyl)benzoic acid | 1154953-17-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((pyridin-3-ylmethyl)carbamoyl)benzoic acid
• 英文别名: 4-(3-pyridylmethylcarbamoyl)benzoic acid；4-(Pyridin-3-ylmethylcarbamoyl)benzoic acid
• CAS: 1154953-17-9
• 化学式: C₁₄H₁₂N₂O₃
• mdl: MFCD12669535
• 分子量: 256.261
• InChiKey: GGRZPNZLSPOYJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  79.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((pyridin-3-ylmethyl)carbamoyl)benzoic acid 、 5,6,7,8-四氢-2-甲基-吡啶并[4,3-d]嘧啶-4(3h)-酮 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-(2-methyl-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidine-6-carbonyl)-N-(3-pyridylmethyl)benzamide
  参考文献：
  名称：

  Analogues of 4-[(7-Bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methylprop-2-ynylamino]-N-(3-pyridylmethyl)benzamide (CB-30865) as Potent Inhibitors of Nicotinamide Phosphoribosyltransferase (Nampt)

  摘要：

  We have shown previously that the target of the potent cytatoxic agent 4-[(7-bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]-N-(3-pyridylmethyl)benzamide (CB38065, 1) is nicotinamide phosphoribosyltransferase (Nampt). With its cellular target known we sought to optimize the biochemical and cellular Nampt activity of 1 as well as its cytotoxicity. It was found that a 3-pyridyl-methylamide substituent in the A region was critical to cellular Nampt activity and cytotoxicity, although other aromatic substitution did yield compounds with submicromolar enzymatic inhibition. Small unsaturated groups worked best in the D-region of the molecule, with 3,3-dimethylallyl providing optimal potency. The E region required a quinazolin-4-one or 1,2,3-benzotriazin-4-one group for activity, and many substituents were tolerated at C(2) of the quinazolin-4-one. The best compounds showed subnanomolar inhibition of Nampt and low nanomolar cytotoxicity in cellular assays.

  DOI：

  10.1021/jm101145b
• 作为产物：
  描述：

  3-氨甲基吡啶 、 对苯二甲酸单甲酯 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide monohydrate 作用下， 以 N,N-二甲基甲酰胺 、 四氢呋喃 、 水 为溶剂， 反应 20.0h， 生成 4-((pyridin-3-ylmethyl)carbamoyl)benzoic acid
  参考文献：
  名称：

  吡嗪连接的 2-氨基苯甲酰胺作为新型 I 类组蛋白脱乙酰酶 (HDAC) 抑制剂的对接、结合自由能计算和体外表征

  摘要：

  I 类组蛋白去乙酰化酶 HDAC1、HDAC2 和 HDAC3 代表了癌症治疗的潜在目标。然而，由于它们的高度序列和结构相似性，为这些酶开发异构体选择性药物仍然具有挑战性。在目前的研究中，我们应用了一种计算方法来预测开发的抑制剂的选择性特征。对包含 30 种先前开发的抑制剂的 2-氨基苯甲酰胺数据集进行分子对接，然后进行 MD 模拟和结合自由能计算。对于每种 HDAC 异构体​​，发现结合自由能值和体外抑制活性之间存在显着相关性。在新设计和合成的抑制剂的外部测试集上评估了最佳预成型模型的预测准确性和可靠性。

  DOI：

  10.3390/molecules27082526

文献信息

• Analogues of 4-[(7-Bromo-2-methyl-4-oxo-3<i>H</i>-quinazolin-6-yl)methylprop-2-ynylamino]-<i>N</i>-(3-pyridylmethyl)benzamide (CB-30865) as Potent Inhibitors of Nicotinamide Phosphoribosyltransferase (Nampt)
  作者：Jeffrey W. Lockman、Brett R. Murphy、Daniel F. Zigar、Weston R. Judd、Paul M. Slattum、Zhong-Hua Gao、Kirill Ostanin、Jeremy Green、Rena McKinnon、Ryan T. Terry-Lorenzo、Tracey C. Fleischer、J. Jay Boniface、Mark Shenderovich、J. Adam Willardsen

  DOI：10.1021/jm101145b

  日期：2010.12.23

  We have shown previously that the target of the potent cytatoxic agent 4-[(7-bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]-N-(3-pyridylmethyl)benzamide (CB38065, 1) is nicotinamide phosphoribosyltransferase (Nampt). With its cellular target known we sought to optimize the biochemical and cellular Nampt activity of 1 as well as its cytotoxicity. It was found that a 3-pyridyl-methylamide substituent in the A region was critical to cellular Nampt activity and cytotoxicity, although other aromatic substitution did yield compounds with submicromolar enzymatic inhibition. Small unsaturated groups worked best in the D-region of the molecule, with 3,3-dimethylallyl providing optimal potency. The E region required a quinazolin-4-one or 1,2,3-benzotriazin-4-one group for activity, and many substituents were tolerated at C(2) of the quinazolin-4-one. The best compounds showed subnanomolar inhibition of Nampt and low nanomolar cytotoxicity in cellular assays.
• Docking, Binding Free Energy Calculations and In Vitro Characterization of Pyrazine Linked 2-Aminobenzamides as Novel Class I Histone Deacetylase (HDAC) Inhibitors
  作者：Emre F. Bülbül、Jelena Melesina、Hany S. Ibrahim、Mohamed Abdelsalam、Anita Vecchio、Dina Robaa、Matthes Zessin、Mike Schutkowski、Wolfgang Sippl

  DOI：10.3390/molecules27082526

  日期：——

  Class I histone deacetylases, HDAC1, HDAC2, and HDAC3, represent potential targets for cancer treatment. However, the development of isoform-selective drugs for these enzymes remains challenging due to their high sequence and structural similarity. In the current study, we applied a computational approach to predict the selectivity profile of developed inhibitors. Molecular docking followed by MD simulation

  I 类组蛋白去乙酰化酶 HDAC1、HDAC2 和 HDAC3 代表了癌症治疗的潜在目标。然而，由于它们的高度序列和结构相似性，为这些酶开发异构体选择性药物仍然具有挑战性。在目前的研究中，我们应用了一种计算方法来预测开发的抑制剂的选择性特征。对包含 30 种先前开发的抑制剂的 2-氨基苯甲酰胺数据集进行分子对接，然后进行 MD 模拟和结合自由能计算。对于每种 HDAC 异构体​​，发现结合自由能值和体外抑制活性之间存在显着相关性。在新设计和合成的抑制剂的外部测试集上评估了最佳预成型模型的预测准确性和可靠性。