N-(2-chloro-4-nitrophenyl)-2-naphthamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(2-chloro-4-nitrophenyl)-2-naphthamide
• 英文别名: N-(2-chloro-4-nitrophenyl)naphthalene-2-carboxamide
• 化学式: C₁₇H₁₁ClN₂O₃
• 分子量: 326.739
• InChiKey: RXCBRQDPFKLPRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氯-4-硝基苯胺 、 2-萘甲酸 在 三氯化磷 作用下， 以 甲苯 为溶剂， 以52%的产率得到N-(2-chloro-4-nitrophenyl)-2-naphthamide
  参考文献：
  名称：

  <p>Reversible Small Molecule Inhibitors of MAO A and MAO B with Anilide Motifs</p>

  摘要：

  Background: Ligands consisting of two aryl moieties connected via a short spacer were shown to be potent inhibitors of monoamine oxidases (MAO) A and B, which are known as suitable targets in treatment of neurological diseases. Based on this general blueprint, we synthesized a series of 66 small aromatic amide derivatives as novel MAO A/B inhibitors.Methods: The compounds were synthesized, purified and structurally confirmed by spectroscopic methods. Fluorimetric enzymological assays were performed to determine MAO A/B inhibition properties. Mode and reversibility of inhibition was determined for the most potent MAO B inhibitor. Docking poses and pharmacophore models were generated to confirm the in vitro results.Results: N-(2,4-Dinitrophenyl)benzo [d] [1,3]dioxole-5-carboxamide (55, ST-2043) was found to be a reversible competitive moderately selective MAO B inhibitor (IC50 = 56 nM, K-i = 6.3 nM), while N-(2,4-dinitrophenyl)benzamide (7, ST-2023) showed higher preference for MAO A (IC50 = 126 nM). Computational analysis confirmed in vitro binding properties, where the anilides examined possessed high surface complementarity to MAO A/B active sites.Conclusion: The small molecule anilides with different substitution patterns were identified as potent MAO A/B inhibitors, which were active in nanomolar concentrations ranges. These small and easily accessible molecules are promising motifs, especially for newly designed multitargeted ligands taking advantage of these fragments.

  DOI：

  10.2147/dddt.s236586

文献信息

• &lt;p&gt;Reversible Small Molecule Inhibitors of MAO A and MAO B with Anilide Motifs&lt;/p&gt;
  作者：Jens Hagenow、Stefanie Hagenow、Kathrin Grau、Mohammad Khanfar、Lena Hefke、Ewgenij Proschak、Holger Stark

  DOI：10.2147/dddt.s236586

  日期：——

  Background: Ligands consisting of two aryl moieties connected via a short spacer were shown to be potent inhibitors of monoamine oxidases (MAO) A and B, which are known as suitable targets in treatment of neurological diseases. Based on this general blueprint, we synthesized a series of 66 small aromatic amide derivatives as novel MAO A/B inhibitors.Methods: The compounds were synthesized, purified and structurally confirmed by spectroscopic methods. Fluorimetric enzymological assays were performed to determine MAO A/B inhibition properties. Mode and reversibility of inhibition was determined for the most potent MAO B inhibitor. Docking poses and pharmacophore models were generated to confirm the in vitro results.Results: N-(2,4-Dinitrophenyl)benzo [d] [1,3]dioxole-5-carboxamide (55, ST-2043) was found to be a reversible competitive moderately selective MAO B inhibitor (IC50 = 56 nM, K-i = 6.3 nM), while N-(2,4-dinitrophenyl)benzamide (7, ST-2023) showed higher preference for MAO A (IC50 = 126 nM). Computational analysis confirmed in vitro binding properties, where the anilides examined possessed high surface complementarity to MAO A/B active sites.Conclusion: The small molecule anilides with different substitution patterns were identified as potent MAO A/B inhibitors, which were active in nanomolar concentrations ranges. These small and easily accessible molecules are promising motifs, especially for newly designed multitargeted ligands taking advantage of these fragments.