4-Hydroxy-N-(2,6-dimethylphenyl)benzamide | 51616-07-0

• 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-Hydroxy-N-(2,6-dimethylphenyl)benzamide
• 英文别名: N-(2,6-dimethylphenyl)-4-hydroxybenzamide；Benzamide, N-(2,6-dimethylphenyl)-4-hydroxy-
• CAS: 51616-07-0
• 化学式: C₁₅H₁₅NO₂
• mdl: MFCD11523392
• 分子量: 241.29
• InChiKey: AFSOCTSNUFCJTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-Hydroxy-N-(2,6-dimethylphenyl)benzamide 、 2-氯-N-[(4-甲氧基苯基)甲基]乙酰胺 在 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 为溶剂， 反应 12.0h， 以18.84%的产率得到N-(2,6-dimethylphenyl)-4-(2-((4-methoxybenzyl)amino)-2-oxoethoxy)benzamide
  参考文献：
  名称：

  骨髓嗜生态病毒整合位点 1 抑制剂的先导优化和构效关系研究

  摘要：

  我们之前的研究结果报道了骨髓嗜嗜性病毒整合位点 1 (MEIS1) 转录因子在心脏再生和造血干细胞 (HSC) 调节中的关键作用。MEIS1 作为药理抑制背景下的一个有希望的靶点，我们鉴定了一种有效的髓系亲嗜性病毒整合位点 (MEIS) 抑制剂 MEISi-1，可在体外和体内诱导小鼠和人类 HSC 扩增。在这项工作中，我们通过合成 45 种新型类似物对 MEISi-1 进行了先导优化。构效关系研究揭示了环A上的对甲氧基和环B间位的疏水部分的重要性. 获得的生物学数据得到了抑制剂对接和分子动力学模拟研究的支持。11 种化合物被描述为强效抑制剂，证明对 MEIS1 和靶基因Meis1、Hif-1 α 和p21具有更好的抑制作用。其中，4h、4f和4b是最有效的抑制剂。预测的药代动力学特性满足药物相似性标准。此外，化合物对人皮肤成纤维细胞既没有细胞毒性，也没有致突变性。

  DOI：

  10.1021/acs.jmedchem.1c00972
• 作为产物：
  描述：

  N-(2,6-二甲基苯基)-4-甲氧基苯甲酰胺 在 三溴化硼 作用下， 以 二氯甲烷 、 水 为溶剂， 以80%的产率得到4-Hydroxy-N-(2,6-dimethylphenyl)benzamide
  参考文献：
  名称：

  Anticonvulsant agents using cyano dimethylphenyl benzamides

  摘要：

  这项发明提供了一些4-取代苯甲酰胺衍生物，它们的药物制剂，以及它们作为抗惊厥剂的使用。

  公开号：

  US04835181A1

文献信息

• Anticonvulsant agents
  申请人：Eli Lilly and Company

  公开号：US04939163A1

  公开（公告）日：1990-07-03

  This invention provides certain 4-substituted benzamide derivatives, their pharmaceutical formulations, and their use as anticonvulsant agents.

  这项发明提供了某些4-取代苯甲酰胺衍生物、它们的制药配方以及它们作为抗惊厥剂的用途。
• Anticonvulsant Activity and Interactions with Neuronal Voltage-Dependent Sodium Channel of Analogues of Ameltolide
  作者：Joseph Vamecq、Didier Lambert、Jacques H. Poupaert、Bernard Masereel、James P. Stables

  DOI：10.1021/jm9608772

  日期：1998.8.1

  Fifteen compounds related to ameltolide (LY 201116) were studied for (i) anticonvulsant potential in the maximal electroshock-induced seizures (MES) and the subcutaneous pentylenetetrazol (sc Ptz) tests in mice and rats and (ii) interactions with neuronal voltage-dependent sodium channels. Compounds were chosen ranging in anticonvulsant activity in mice from very active to inactive. The active compounds were defined as those protecting 50% of the animals at doses between 10 and 50 mu mol/kg and inactive compounds as those protecting 50% of the animals at doses greater than 1 mmol/kg. The series studied included three N-(2,6-dimethylphenyl)benzamides (compounds 1, 2 (ameltolide), and 3), three N-(2,2,6,6-tetramethyl)piperidinyl-4-benzamides (compounds 4, 5, 6), one phenylthiourea (compound 7), five N-(2,6-dimethylphenyl)phthalimides (compounds 8, 9, 10, 13, and 14), two N-phenylphthalimide derivatives (compounds 11 and 12), and one N-(2,2,6,6-tetramethyl)piperidinyl-4-phtalimide (compound 15). Phenytoin (PHT) was employed as the reference prototype antiepileptic drug. After inital screening in mice, compounds 1, 2, 3, 5, 8, 9, 10, 13, and 14 were selected for further testing in rats. Anticonvulsant ED(50)s (effective doses in at least 50% of animals tested) of compounds in the MES test were determined in rats dosed orally and amounted to 52 (1), 135 (2), 284 (3), 31 (8), 131 (9), 25 (10), 369 (13), 354 (14), and 121 (PHT) mu mol/kg, compound 5 presenting with an ED50 value higher than 650 mu mol/kg. In our hands, the apparent IC(50)s (inhibitory concentrations 50) of compounds toward binding to rat brain synaptosomes of [H-3]batrachotoxinin-A-20 alpha-benzoate were 0.25 (1), 0.97 (2), 0.35 (3), 25.8 (5), 161.3 (8), 183.5 (9), 0.11 (10), 1.86 (13), 47.8 (14), and 0.86 (PHT) mu M. The relationship between the activity in the MES test and the capacity to interact in vitro with neuronal voltage-dependent sodium channels and the fact that the IC50 values obtained in the in vitro test are close to the brain concentrations at which anticonvulsant activities are reported to occur for ameltolide strongly suggest that the anticonvulsant properties of most compounds tested could be a direct result of their interaction with the neuronal voltage-dependent sodium channel.
• Synthesis of new polyoxin derivatives and their activity against chitin synthase from Candida albicans
  作者：Gerhard Emmer、Neil S. Ryder、Maximilian A. Grassberger

  DOI：10.1021/jm00381a003

  日期：1985.3

  Two analogues of L-alanylpolyoxin C with a modified peptide bond were synthesized and tested for inhibition of chitin synthase in Candida albicans. N-Methylation of the peptide bond (compound 13) or the replacement of it by NH2CH2 (compound 9) led to loss of activity in the enzyme assay. A novel analogue (compound 5) of nikkomycin was synthesized from uracil polyoxin C and (2S,3R)-3-hydroxyhomotyrosine, a component of echinocandin C. Despite high activity in the chitin synthase assay, 5 had no inhibitory effect on cells of C. albicans.
• BEEDLE, EDWARD E.;ROBERTSON, DAVID W.
  作者：BEEDLE, EDWARD E.、ROBERTSON, DAVID W.

  DOI：——

  日期：——
• US4835181A
  申请人：——

  公开号：US4835181A

  公开（公告）日：1989-05-30