3,4,5-Trimethoxy-N-(3-nitro-phenyl)-benzamide | 6597-38-2

• 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: 3,4,5-Trimethoxy-N-(3-nitro-phenyl)-benzamide
• 英文别名: 3,4,5-Trimethoxy-N-(3-nitrophenyl)benzamide
• CAS: 6597-38-2
• 化学式: C₁₆H₁₆N₂O₆
• mdl: MFCD00587130
• 分子量: 332.313
• InChiKey: XASHOUQQWOXQNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,4,5-Trimethoxy-N-(3-nitro-phenyl)-benzamide 在 palladium 10% on activated carbon 、 甲酸铵 作用下， 以 异丙醇 、 丙酮 为溶剂， 反应 1.0h， 生成 3,4,5-trimethoxy-N-(3-((3,4,5-trimethoxybenzoyl)aminocarbonothioyl)aminophenyl)benzamide
  参考文献：
  名称：

  Acylthiourea, Acylurea, and Acylguanidine Derivatives with Potent Hedgehog Inhibiting Activity

  摘要：

  The Smoothened (Smo) receptor is the major transducer of the Hedgehog (Hh) signaling pathway. On the basis of the structure of the acylthiourea Smo antagonist (MRT-10), a number of different series of analogous compounds were prepared by ligand-based structural optimization. The acylthioureas, originally identified as actives, were converted into the corresponding acylureas or acylguanidines. In each series, similar structural trends delivered potent compounds with IC50 values in the nanomolar range with respect to the inhibition of the Hh signaling pathway in various cell-based assays and of BODIPY-cyclopamine binding to human Smo. The similarity of their biological activities, in spite of discrete structural differences, may reveal the existence of hydrogen-bonding interactions between the ligands and the receptor pocket. Biological potency of compounds 61, 72, and 86 (MRT-83) were comparable to those of the clinical candidate GDC-0449. These findings suggest that these original molecules will help delineate Smo and Hh functions and can be developed as potential anticancer agents.

  DOI：

  10.1021/jm2013369
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲酰氯 、 间硝基苯胺 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以77.41 %的产率得到3,4,5-Trimethoxy-N-(3-nitro-phenyl)-benzamide
  参考文献：
  名称：

  新型苯甲酰胺作为多靶点化合物：合成、AChE 和 BACE1 抑制活性及分子对接研究

  摘要：

  设计了十一种新的和以前未描述的苯甲酰胺的合成。这些化合物被明确预测为乙酰胆碱酯酶 (AChE) 和 β-分泌酶 (BACE1) 的潜在抑制剂。N,N'-(1,4-亚苯基)双(3-甲氧基苯甲酰胺)对AChE最有活性，AChE的抑制浓度IC50 = 0.056 µM，而多奈哌齐的IC50为0.046 µM。该化合物也是对抗 BACE1 酶最活跃的。与槲皮素相比，IC50 值为 9.01 µM，IC50 = 4.89 µM。定量结果表明该衍生物是最有前途的。进行分子建模以阐明该化合物的潜在作用机制。动态模拟表明，新配体对AChE的稳定作用有限，但都明显降低了酶的灵活性。因此，可以得出结论，可能的抑制机制增加了酶的硬度并降低了酶的灵活性，这显然阻碍了其正常功能。对氢键模式的分析表明，当最活跃的衍生物与酶相互作用时，存在不同的机制（与其他配体不同）。

  DOI：

  10.3390/ijms241914901

文献信息

• Kar, Pharmazie, 1983, vol. 38, # 5, p. 313 - 315
  作者：Kar

  DOI：——

  日期：——
• 3-(2′-Bromopropionylamino)-benzamides as novel S-phase arrest agents
  作者：Laixing Hu、Zhuo-rong Li、Jian-Nong Li、Jinrong Qu、Jian-Dong Jiang、David W. Boykin

  DOI：10.1016/j.bmcl.2007.10.016

  日期：2007.12

  We report the synthesis, anti proliferative activity, and SAR of novel 3-(2'-bromopropionylamino)-benzamides. Many of the benzamide compounds showed potent cytotoxicities against Molt-3 leukemia cells. Several compounds exihibited cytotoxicities (under 6.5 mu M) against five solid tumor cell lines. The mechanism of action of the most potent benzamide 101 does not involve targeting on tubulin but it causes cell cycle S-phase arrest. This active S-phase arrest agent merits further investigation. (c) 2007 Elsevier Ltd. All rights reserved.
• KAR, A., PHARMAZIE, 1983, 38, N 5, 313-315
  作者：KAR, A.

  DOI：——

  日期：——
• Acylthiourea, Acylurea, and Acylguanidine Derivatives with Potent Hedgehog Inhibiting Activity
  作者：Antonio Solinas、Hélène Faure、Hermine Roudaut、Elisabeth Traiffort、Angèle Schoenfelder、André Mann、Fabrizio Manetti、Maurizio Taddei、Martial Ruat

  DOI：10.1021/jm2013369

  日期：2012.2.23

  The Smoothened (Smo) receptor is the major transducer of the Hedgehog (Hh) signaling pathway. On the basis of the structure of the acylthiourea Smo antagonist (MRT-10), a number of different series of analogous compounds were prepared by ligand-based structural optimization. The acylthioureas, originally identified as actives, were converted into the corresponding acylureas or acylguanidines. In each series, similar structural trends delivered potent compounds with IC50 values in the nanomolar range with respect to the inhibition of the Hh signaling pathway in various cell-based assays and of BODIPY-cyclopamine binding to human Smo. The similarity of their biological activities, in spite of discrete structural differences, may reveal the existence of hydrogen-bonding interactions between the ligands and the receptor pocket. Biological potency of compounds 61, 72, and 86 (MRT-83) were comparable to those of the clinical candidate GDC-0449. These findings suggest that these original molecules will help delineate Smo and Hh functions and can be developed as potential anticancer agents.