n-(2,5-Dimethylphenyl)-2-nitrobenzamide | 102630-96-6

• 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: n-(2,5-Dimethylphenyl)-2-nitrobenzamide
• CAS: 102630-96-6
• 化学式: C₁₅H₁₄N₂O₃
• 分子量: 270.288
• InChiKey: IGUIIBFKJFKXRE-UHFFFAOYSA-N

物化性质

• 熔点：
  173-175 °C(Solv: benzene (71-43-2))
• 沸点：
  355.1±42.0 °C(Predicted)
• 密度：
  1.270±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 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：

  n-(2,5-Dimethylphenyl)-2-nitrobenzamide 在 sodium hydroxide 、 锌 作用下， 以 甲醇 、 水 为溶剂， 反应 15.0h， 以36%的产率得到2-苯基-1,2-二氢-3H-吲唑-3-酮
  参考文献：
  名称：

  Potent, Selective, and Orally Available Benzoisothiazolone Phosphomannose Isomerase Inhibitors as Probes for Congenital Disorder of Glycosylation Ia

  摘要：

  We report the discovery and validation of a series of benzoisothiazolones as potent inhibitors of phosphomannose isomerase (PM), an enzyme that converts mannose-6-phosphate (Man-6-P) into fructose-6-phosphate (Fru-6-P) and, more importantly, competes with phosphomannomutase 2 (PMM2) for Man-6-P, diverting this substrate from critical protein glycosylation events. In congenital disorder of glycosylation type Ia, PMM2 activity is compromised.; thus, PMI inhibition is a potential strategy for the development of therapeutics. High-throughput screening (HTS) and subsequent chemical optimization led to the identification of a novel class of benzoisothiazolones as potent PMI inhibitors having little or no PMM2 inhibition. Two complementary synthetic routes were developed, enabling the critical structural requirements for activity to be determined, and the compounds were subsequently profiled in biochemical and cellular assays to assess efficacy. The most promising compounds were also profiled for bioavailability parameters, including metabolic stability, plasma stability, and permeability. The pharmacokinetic profile of a representative of this series (compound 19; ML089) was also assessed, demonstrating the potential of this series for in vivo efficacy when dosed orally in disease models.

  DOI：

  10.1021/jm101401a
• 作为产物：
  描述：

  2,5-二甲基苯胺 、 2-硝基苯甲酰氯 在 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以61%的产率得到n-(2,5-Dimethylphenyl)-2-nitrobenzamide
  参考文献：
  名称：

  Anticonvulsant activity of 2- and 3-aminobenzanilides

  摘要：

  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.

  DOI：

  10.1021/jm00158a038

文献信息

• 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：——
• BENZOISOTHIAZOLONES AS INHIBITORS OF PHOSPHOMANNOSE ISOMERASE
  申请人：Cosford Nicholas D. P.

  公开号：US20110257233A1

  公开（公告）日：2011-10-20

  The disclosure provides new compounds and compositions thereof, and methods for treating or ameliorating a disorder relating to CDG-Ia. In particular, the disclosure provides benzoisothiazolone inhibitors of PMI, which have been synthesized and their ability to drive glycosylation has been demonstrated. The disclosure provides two synthetic routes for these compounds, including a new copper-catalyzed N-arylation reaction amenable to parallel derivitization. The disclosed compounds represent potent inhibitors of PMI, and their dose-dependent efficacy in cell-based models of glycosylation have been demonstrated. In addition, the disclosed compounds are selective over PMM and therefore, are useful in treating or ameliorating a disorder relating to CDG-Ia.
• 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.
• Potent, Selective, and Orally Available Benzoisothiazolone Phosphomannose Isomerase Inhibitors as Probes for Congenital Disorder of Glycosylation Ia
  作者：Russell Dahl、Yalda Bravo、Vandana Sharma、Mie Ichikawa、Raveendra-Panickar Dhanya、Michael Hedrick、Brock Brown、Justin Rascon、Michael Vicchiarelli、Arianna Mangravita-Novo、Li Yang、Derek Stonich、Ying Su、Layton H. Smith、Eduard Sergienko、Hudson H. Freeze、Nicholas D. P. Cosford

  DOI：10.1021/jm101401a

  日期：2011.5.26

  We report the discovery and validation of a series of benzoisothiazolones as potent inhibitors of phosphomannose isomerase (PM), an enzyme that converts mannose-6-phosphate (Man-6-P) into fructose-6-phosphate (Fru-6-P) and, more importantly, competes with phosphomannomutase 2 (PMM2) for Man-6-P, diverting this substrate from critical protein glycosylation events. In congenital disorder of glycosylation type Ia, PMM2 activity is compromised.; thus, PMI inhibition is a potential strategy for the development of therapeutics. High-throughput screening (HTS) and subsequent chemical optimization led to the identification of a novel class of benzoisothiazolones as potent PMI inhibitors having little or no PMM2 inhibition. Two complementary synthetic routes were developed, enabling the critical structural requirements for activity to be determined, and the compounds were subsequently profiled in biochemical and cellular assays to assess efficacy. The most promising compounds were also profiled for bioavailability parameters, including metabolic stability, plasma stability, and permeability. The pharmacokinetic profile of a representative of this series (compound 19; ML089) was also assessed, demonstrating the potential of this series for in vivo efficacy when dosed orally in disease models.

表征谱图