3-nitro-N-m-tolyl-benzamide | 69754-50-3

• 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: 3-nitro-N-m-tolyl-benzamide
• 英文别名: 3-nitro-N-3-tolylbenzamide；3-nitro-benzoic acid m-toluidide；3-Nitro-benzoesaeure-m-toluidid；3-Nitro-benzoesaeure-m-toluidid；N-(3-methylphenyl)-3-nitrobenzamide
• CAS: 69754-50-3
• 化学式: C₁₄H₁₂N₂O₃
• mdl: MFCD00437403
• 分子量: 256.261
• InChiKey: PZZACBBPLIOFMI-UHFFFAOYSA-N

物化性质

• 熔点：
  115-118 °C(Solv: benzene (71-43-2))
• 沸点：
  338.8±35.0 °C(Predicted)
• 密度：
  1.304±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-nitro-N-m-tolyl-benzamide 在 盐酸 、 tin(II) chloride dihdyrate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 水 、 丙酮 为溶剂， 反应 0.17h， 生成 methyl 3-(3-(3-(m-tolylcarbamoyl)phenyl)ureido)benzoate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of suramin-derived dual antagonists of the proinflammatory G protein-coupled receptors P2Y2 and GPR17

  摘要：

  Dual- or multi-target drugs are particularly promising for the treatment of complex diseases such as (neuro)inflammatory disorders. In the present study, we identified dual antagonists for two related proinflammatory G protein-coupled receptors (GPCRs), the purinergic receptor P2Y(2) receptor, and the orphan receptor GPR17. Based on the lead compound suramin small molecules were designed, synthesized, and modified, including benzenesulfonate, benzenesulfonamide, dibenzamide and diphenylurea derivatives. Structure-activity relationship studies identified 3-nitrophenyl 4-benzamidobenzenesulfonic acid derivatives as dual P2Y(2)R/GPR17 antagonists. In particular, 3-nitrophenyl 4-(4-chlorobenzamido) benzenesulfonate (14l, IC50 3.01 mu M at P2Y(2)R, and 3.37 mu M at GPR17) and 3-nitrophenyl-4-(2-chlorobenzamido)benzenesulfonate (14m, IC50 3.17 mu M at P2Y(2)R, and 1.67 mu M at GPR17) exhibited dual antagonistic activity. Compound 14l was shown to act as an allosteric antagonist at both receptors. In addition, GPR17-selective antagonists were identified( )including 3-nitrophenyl 4-benzamidobenzenesulfonate (14a, IC50 3.20 mu M) and 3-nitrophenyl 4-(3-(trifluoromethyl)benzamido) benzenesulfonate (14f, IC50 3.88 mu M). The developed antagonists were selective versus other closely related P2Y receptors. They were found to possess high chemical and metabolic stability in human liver microsomes and therefore present good starting points for developing potent multi-target drugs with potential applications in inflammatory diseases. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111789
• 作为产物：
  描述：

  间硝基苯甲酸 在 氯化亚砜 、 sodium carbonate 作用下， 以 乙醚 为溶剂， 生成 3-nitro-N-m-tolyl-benzamide
  参考文献：
  名称：

  N-苯甲酰基氨基萘的分子内电荷转移。1-氨基萘与2-氨基萘作为电子给体。

  摘要：

  制备了在苯甲酰基苯环的对位或间位具有不同取代基的N-（取代-苯甲酰基）-1-氨基萘和N-（取代-苯甲酰基）-2-氨基萘（1-NBA和2-NBA）使用类苯甲酰苯胺电荷转移作为探针反应，探测1-氨基萘（1-AN）和2-氨基萘（2-AN）之间的差异。对于在环己烷中所有制备的氨基萘衍生物，发现了异常的长波发射，并且通过观察到随着溶剂极性的增加或取代基的吸电子能力的增加而发生的大幅度红移，将其分配为CT状态。发现CT发射能量与取代基的Hammett常数和1-NBA（-0。45 eV高于2-NBA（-0.35 eV），后者与苯胺衍生物（BAs，-0.345 eV）接近。这表明在1-NBA的CT状态下，电荷分离的程度更高，其中完全放电分离是通过CT发射能量的线性下降率为-1.00的降低电势依赖性建立的。通过观察发现，当对位，间位和对位时，苯甲酰基取代的BA的相应线性斜率保持不变，从而排除了1-NBA和2

  DOI：

  10.1039/b210106h

文献信息

• Elaborate ligand-based pharmacophore exploration and QSAR analysis guide the synthesis of novel pyridinium-based potent β-secretase inhibitory leads
  作者：Afaf Al-Nadaf、Ghassan Abu Sheikha、Mutasem O. Taha

  DOI：10.1016/j.bmc.2010.03.043

  日期：2010.5

  beta-Secretase (BACE) inhibitors have potential as anti-Alzheimer's disease treatments prompting us to explore the pharmacophoric space of 129 known BACE inhibitors. QSAR analysis was employed to select optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of explaining bioactivity variation (r(2) = 0.88, F = 60.48, r(LOO)(2) = 0.85, r(PRESS)(2) against 25 external test inhibitors = 0.71). We were obliged to use ligand efficiency as the response variable because the logarithmic transformation of bioactivities failed to access self-consistent QSAR models. Three pharmacophoric models emerged in the successful QSAR equation suggesting at least three binding modes accessible to ligands within BACE binding pocket. QSAR equation and pharmacophoric models were validated through ROC curves and were employed to guide synthesis of novel pyridinium-based BACE inhibitors. The best inhibitor illustrated an IC50 value of 1.0 mu M against BACE. (c) 2010 Elsevier Ltd. All rights reserved.
• Anticonvulsant activity of 2- and 3-aminobenzanilides
  作者：C. Randall Clark、Ching Ming Lin、Ricky T. Sansom

  DOI：10.1021/jm00158a038

  日期：1986.8

  A series of 2- and 3-aminobenzanilides derived from ring-alkylated anilines were prepared and evaluated for anticonvulsant activity. These benzanilides were prepared in the course of studies designed to determine the relationship between the benzamide structure and anticonvulsant effects. The compounds were tested in mice against seizures induced by maximal electroshock (MES) and pentylenetetrazole and in the rotorod assay for neurologic deficit. The 3-aminobenzanilide derived from 2,6-dimethylaniline, 21, was the most potent anti-MES compound, with an ED50 of 13.48 mg/kg and a protective index of 21.11 (PI = TD50/ED50). The activity profile for 21 compares favorably with that for phenobarbital and phenytoin.
• CLARK C. R.; LING CHING-MING; SANSOM R. T., J. MED. CHEM., 29,(1986) N 8, 1534-1537
  作者：CLARK C. R.、 LING CHING-MING、 SANSOM R. T.

  DOI：——

  日期：——
• Intramolecular charge transfer with N-benzoylaminonaphthalenes. 1-Aminonaphthalene versus 2-aminonaphthalene as electron donors
  作者：Xuan Zhang、Chun-Hua Liu、Li-Hong Liu、Fang-Ying Wu、Lin Guo、Xiang-Ying Sun、Chao-Jie Wang、Yun-Bao Jiang

  DOI：10.1039/b210106h

  日期：2003.2.11

  derivatives in cyclohexane and was assigned to the CT state by the observation of a substantial red shift with increasing solvent polarity or with increasing electron-withdrawing ability of the substituent. The CT emission energies were found to follow a linear relationship with the Hammett constant of the substituent and the value of the linear slope for 1-NBAs (-0.45 eV) was higher than that of 2-NBAs (-0

  制备了在苯甲酰基苯环的对位或间位具有不同取代基的N-（取代-苯甲酰基）-1-氨基萘和N-（取代-苯甲酰基）-2-氨基萘（1-NBA和2-NBA）使用类苯甲酰苯胺电荷转移作为探针反应，探测1-氨基萘（1-AN）和2-氨基萘（2-AN）之间的差异。对于在环己烷中所有制备的氨基萘衍生物，发现了异常的长波发射，并且通过观察到随着溶剂极性的增加或取代基的吸电子能力的增加而发生的大幅度红移，将其分配为CT状态。发现CT发射能量与取代基的Hammett常数和1-NBA（-0。45 eV高于2-NBA（-0.35 eV），后者与苯胺衍生物（BAs，-0.345 eV）接近。这表明在1-NBA的CT状态下，电荷分离的程度更高，其中完全放电分离是通过CT发射能量的线性下降率为-1.00的降低电势依赖性建立的。通过观察发现，当对位，间位和对位时，苯甲酰基取代的BA的相应线性斜率保持不变，从而排除了1-NBA和2
• Design, synthesis and biological evaluation of suramin-derived dual antagonists of the proinflammatory G protein-coupled receptors P2Y2 and GPR17
  作者：Thanigaimalai Pillaiyar、Mario Funke、Haneen Al-Hroub、Stefanie Weyler、Sabrina Ivanova、Jonathan Schlegel、Aliaa Abdelrahman、Christa E. Müller

  DOI：10.1016/j.ejmech.2019.111789

  日期：2020.1

  Dual- or multi-target drugs are particularly promising for the treatment of complex diseases such as (neuro)inflammatory disorders. In the present study, we identified dual antagonists for two related proinflammatory G protein-coupled receptors (GPCRs), the purinergic receptor P2Y(2) receptor, and the orphan receptor GPR17. Based on the lead compound suramin small molecules were designed, synthesized, and modified, including benzenesulfonate, benzenesulfonamide, dibenzamide and diphenylurea derivatives. Structure-activity relationship studies identified 3-nitrophenyl 4-benzamidobenzenesulfonic acid derivatives as dual P2Y(2)R/GPR17 antagonists. In particular, 3-nitrophenyl 4-(4-chlorobenzamido) benzenesulfonate (14l, IC50 3.01 mu M at P2Y(2)R, and 3.37 mu M at GPR17) and 3-nitrophenyl-4-(2-chlorobenzamido)benzenesulfonate (14m, IC50 3.17 mu M at P2Y(2)R, and 1.67 mu M at GPR17) exhibited dual antagonistic activity. Compound 14l was shown to act as an allosteric antagonist at both receptors. In addition, GPR17-selective antagonists were identified( )including 3-nitrophenyl 4-benzamidobenzenesulfonate (14a, IC50 3.20 mu M) and 3-nitrophenyl 4-(3-(trifluoromethyl)benzamido) benzenesulfonate (14f, IC50 3.88 mu M). The developed antagonists were selective versus other closely related P2Y receptors. They were found to possess high chemical and metabolic stability in human liver microsomes and therefore present good starting points for developing potent multi-target drugs with potential applications in inflammatory diseases. (C) 2019 Elsevier Masson SAS. All rights reserved.