N-(3,4-dimethyl-2H-2-oxochromen-7-yl)-4-methylbenzenesulfonamide | 320350-70-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: N-(3,4-dimethyl-2H-2-oxochromen-7-yl)-4-methylbenzenesulfonamide
• 英文别名: N-(3,4-dimethyl-2-oxochromen-7-yl)-4-methylbenzenesulfonamide
• CAS: 320350-70-7
• 化学式: C₁₈H₁₇NO₄S
• 分子量: 343.403
• InChiKey: GGVVUZKWLRJYDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3,4-dimethyl-2H-2-oxochromen-7-yl)-4-methylbenzenesulfonamide 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以83%的产率得到N-(3,4-Dimethyl-2-oxo-2H-chromen-7-yl)-4,N-dimethyl-benzenesulfonamide
  参考文献：
  名称：

  Structural Insights into Monoamine Oxidase Inhibitory Potency and Selectivity of 7-Substituted Coumarins from Ligand- and Target-Based Approaches

  摘要：

  A new series of 3-, 4-, 7-polysubstituted coumarins have been designed and evaluated for their monoamine oxidase A and monoamine oxidase B (MAO-A and MAO-B) inhibitory potency. Substituents at position 7 consisted of a bridge of different physicochemical nature linking a phenyl ring to the coumarin scaffold. Structure-affinity and structure-selectivity relationships, derived through CoMFA-GOLPE and docking studies, revealed the key physicochemical interactions responsible for the observed MAO-B and MAO-A inhibitory potency and suggested the main structural determinants for high selectivity toward one of the two enzymatic isoforms. The predictive power of our models was proved with the design of a new inhibitor demonstrating an outstanding MAO-B affinity (pIC(50) = 8.29) and the highest MAO-B selectivity (Delta pIC(50) = 3.39) within the entire series of ligands examined herein.

  DOI：

  10.1021/jm060183l
• 作为产物：
  描述：

  3-氨基苯酚 在 吡啶 、 zinc(II) chloride 作用下， 以 乙醇 为溶剂， 反应 1.5h， 生成 N-(3,4-dimethyl-2H-2-oxochromen-7-yl)-4-methylbenzenesulfonamide
  参考文献：
  名称：

  Inhibition of Monoamine Oxidases by Functionalized Coumarin Derivatives:  Biological Activities, QSARs, and 3D-QSARs

  摘要：

  A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory activity. Most of the compounds acted preferentially on MAO-B with IC50 values in the micromolar to low-nanomolar range; high inhibitory activities toward MAO-A were also measured for sulfonic acid esters. The most active compound was 7-[(3,4-difluorobenzyl)oxy]-3,4-dimethylcoumarin, with an IC50 value toward MAO-B of 1.14 nM. A QSAR study of 7-X-benzyloxy meta-substituted 3,4-dimethylcoumarin derivatives acting on MAO-B yielded good statistical results (q(2) = 0.72, r(2) = 0.86), revealing the importance of lipophilic interactions in modulating the inhibition and excluding any dependence on electronic properties. CoMFA was performed on two data sets of MAO-A and MAO-B inhibitors. The GOLPE procedure, with variable selection criteria, was applied to improve the predictivity of the models and to facilitate the graphical interpretation of results.

  DOI：

  10.1021/jm001028o

文献信息

• Structural Insights into Monoamine Oxidase Inhibitory Potency and Selectivity of 7-Substituted Coumarins from Ligand- and Target-Based Approaches
  作者：Marco Catto、Orazio Nicolotti、Francesco Leonetti、Andrea Carotti、Angelo Danilo Favia、Ramón Soto-Otero、Estefanía Méndez-Álvarez、Angelo Carotti

  DOI：10.1021/jm060183l

  日期：2006.8.1

  A new series of 3-, 4-, 7-polysubstituted coumarins have been designed and evaluated for their monoamine oxidase A and monoamine oxidase B (MAO-A and MAO-B) inhibitory potency. Substituents at position 7 consisted of a bridge of different physicochemical nature linking a phenyl ring to the coumarin scaffold. Structure-affinity and structure-selectivity relationships, derived through CoMFA-GOLPE and docking studies, revealed the key physicochemical interactions responsible for the observed MAO-B and MAO-A inhibitory potency and suggested the main structural determinants for high selectivity toward one of the two enzymatic isoforms. The predictive power of our models was proved with the design of a new inhibitor demonstrating an outstanding MAO-B affinity (pIC(50) = 8.29) and the highest MAO-B selectivity (Delta pIC(50) = 3.39) within the entire series of ligands examined herein.
• Inhibition of Monoamine Oxidases by Functionalized Coumarin Derivatives:  Biological Activities, QSARs, and 3D-QSARs
  作者：Carmela Gnerre、Marco Catto、Francesco Leonetti、Peter Weber、Pierre-Alain Carrupt、Cosimo Altomare、Angelo Carotti、Bernard Testa

  DOI：10.1021/jm001028o

  日期：2000.12.1

  A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory activity. Most of the compounds acted preferentially on MAO-B with IC50 values in the micromolar to low-nanomolar range; high inhibitory activities toward MAO-A were also measured for sulfonic acid esters. The most active compound was 7-[(3,4-difluorobenzyl)oxy]-3,4-dimethylcoumarin, with an IC50 value toward MAO-B of 1.14 nM. A QSAR study of 7-X-benzyloxy meta-substituted 3,4-dimethylcoumarin derivatives acting on MAO-B yielded good statistical results (q(2) = 0.72, r(2) = 0.86), revealing the importance of lipophilic interactions in modulating the inhibition and excluding any dependence on electronic properties. CoMFA was performed on two data sets of MAO-A and MAO-B inhibitors. The GOLPE procedure, with variable selection criteria, was applied to improve the predictivity of the models and to facilitate the graphical interpretation of results.