2-nitro-5-(pyrrolidin-1-yl)benzamide | 299897-90-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 2-nitro-5-(pyrrolidin-1-yl)benzamide
• 英文别名: 2-nitro-5-pyrrolidin-1-ylbenzamide；5-(1-pyrrolidino)-2-nitrobenzamide；2-Nitro-5-(1-pyrrolidinyl)benzenecarboxamide
• CAS: 299897-90-8
• 化学式: C₁₁H₁₃N₃O₃
• 分子量: 235.243
• InChiKey: AAZGZPUPRNPHNJ-UHFFFAOYSA-N

物化性质

• 熔点：
  246-248°C

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  92.2
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-nitro-5-(pyrrolidin-1-yl)benzamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 2-amino-5-(pyrrolidin-1-yl)benzamide
  参考文献：
  名称：

  6-吡咯烷基-2-(2-取代苯基)-4-喹唑啉酮的合成及细胞毒性

  摘要：

  在我们继续寻找潜在的抗癌候选药物时，选择了 2-(3-甲氧基苯基)-6-吡咯烷基-4-喹唑啉酮 (JJC-1) 作为先导化合物。起始 5-吡咯烷基-2-氨基苯甲酰胺使用标准方法由 5-氯-2-硝基苯甲酸通过与 SOCl2、NH3、吡咯烷和 H2 反应制备。然后在 NaHSO3 存在下，在 N,N-二甲基乙酰胺 (DMAC) 中使起始苯甲酰胺与 2-取代苯甲醛或苯甲酰氯在 150 °C 下反应。热环脱水/脱氢得到目标 6-吡咯烷基-2-(2-取代的苯基)-4-喹唑啉酮 (15-22)。这些目标化合物在体外对六种癌细胞系进行了细胞毒性分析，包括人单核细胞白血病细胞 (U937)、小鼠单核细胞白血病细胞 (WEHI-3)、人肝癌细胞 (HepG2、Hep3B) 和人肺癌细胞 (A549, CH27)。它们中的大多数对U937和WEHI-3细胞表现出显着的细胞毒作用，EC50值范围为0.30至10

  DOI：

  10.1002/jccs.200700113
• 作为产物：
  描述：

  5-氯-2-硝基苯甲酸 在 氯化亚砜 、 氨 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 7.0h， 生成 2-nitro-5-(pyrrolidin-1-yl)benzamide
  参考文献：
  名称：

  6-Alkylamino- and 2,3-Dihydro-3‘-methoxy-2-phenyl-4-quinazolinones and Related Compounds:  Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization

  摘要：

  As part of our continuing search for potential anticancer candidates among 2-phenyl-4-quinolones and 2-phenyl-4-quinazolinones, two series of 6,7,2',3',4',5'-substituted 2-phenyl-4-quinazolinones and 6,2',3',4',5'-substituted 2,3-dihydro-2-phenyl-4-quinazolinones were synthesized and evaluated for cytotoxicity and as inhibitors of tubulin polymerization. In general, a good correlation was found between the two activities. Five of the 6-substituted heterocyclic 2-phenyl-4-quinozolinones (37-51) showed significant cytotoxicity against a panel of human tumor cell lines with EC50 values in the low micromolar to nanomolar concentration ranges. Compound 38 was the most potent of these compounds, as well as the most potent inhibitor of tubulin polymerization in this series. The activity of 38 was in the same range as those of the antimitotic natural products, colchicine, podophyllotoxin, and combretastatin A-4. Substituted 2-phenyl-4-quinazolinones and 2,3-dihydro-2-phenyl-4-quinazolinones also displayed highly selective cytotoxicity against the ovarian cancer 1A9 and P-gp resistant KB-VIN cell lines.

  DOI：

  10.1021/jm000151c

文献信息

• [EN] GLUCOSE UPTAKE INHIBITORS<br/>[FR] INHIBITEURS DE L'ABSORPTION DU GLUCOSE
  申请人：KADMON CORP LLC

  公开号：WO2020005935A1

  公开（公告）日：2020-01-02

  This invention provides compounds that modulate glucose uptake activity and cellular transport/uptake of glucose, and particularly GLUTS3, but also including but not limited to GLUT1-14 (SLC2A1-SLC2A14). Compounds of the invention are useful for treating diseases, including cancer, autoimmune diseases and inflammation, infectious diseases, and metabolic diseases.

  这项发明提供了一种调节葡萄糖摄取活性和细胞对葡萄糖的运输/摄取的化合物，尤其是GLUTS3，但也包括但不限于GLUT1-14（SLC2A1-SLC2A14）。发明中的化合物可用于治疗包括癌症、自身免疫性疾病和炎症、感染性疾病以及代谢性疾病。
• A Simple One-Pot Synthesis of 2-Substituted Quinazolin-4(3H)-ones from 2-Nitrobenzamides by Using Sodium Dithionite
  作者：Simón López、Angel Romero、José Salazar

  DOI：10.1055/s-0033-1338854

  日期：——

  simple one-pot procedure for the preparation of 2-(het)arylquinazolin-4(3H)-ones starting from readily available 2-nitrobenzamides and (het)aryl aldehydes is described. Sodium dithionite is used as the reducing agent for the nitro group, and its decomposition in situ in aqueous N,N-dimethylformamide leads to the final oxidation step that gives the desired heterocyclic compounds. A simple one-pot procedure

  摘要 描述了从容易获得的2-硝基苯甲酰胺和（杂）芳基醛开始制备2-（杂）芳基喹唑啉-4（3H）-的简单的一锅法。将连二亚硫酸钠用作硝基的还原剂，其在N，N-二甲基甲酰胺水溶液中的原位分解导致最终的氧化步骤得到所需的杂环化合物。 描述了从容易获得的2-硝基苯甲酰胺和（杂）芳基醛开始制备2-（杂）芳基喹唑啉-4（3H）-的简单的一锅法。将连二亚硫酸钠用作硝基的还原剂，其在N，N-二甲基甲酰胺水溶液中的原位分解导致最终的氧化步骤得到所需的杂环化合物。
• Molecular modelling, synthesis, cytotoxicity and anti-tumour mechanisms of 2-aryl-6-substituted quinazolinones as dual-targeted anti-cancer agents
  作者：M J Hour、K H Lee、T L Chen、K T Lee、Yu Zhao、H Z Lee

  DOI：10.1111/bph.12233

  日期：2013.8

  Background and PurposeOur previous study demonstrated that 6‐(pyrrolidin‐1‐yl)‐2‐(3‐methoxyphenyl)quinazolin‐4‐one (HMJ38) was a potent anti‐tubulin agent. Here, HMJ38 was used as a lead compound to develop more potent anti‐cancer agents and to examine the anti‐cancer mechanisms.Experimental ApproachUsing computer‐aided drug design, 2‐aryl‐6‐substituted quinazolinones (MJ compounds) were designed and synthesized by introducing substituents at C‐2 and C‐6 positions of HMJ38. The cytotoxicity of MJ compounds towards human cancer cells was examined by Trypan blue exclusion assay. Microtubule distribution was visualized using TubulinTrackerTM Green reagent. Protein expression of cell cycle regulators and JNK was assessed by Western blot analysis.Key ResultsCompounds MJ65–70 exhibited strong anti‐proliferative effects towards melanoma M21, lung squamous carcinoma CH27, lung non‐small carcinoma H460, hepatoma Hep3B and oral cancer HSC‐3 cells, with one compund MJ66 (6‐(pyrrolidin‐1‐yl)‐2‐(naphthalen‐1‐yl)quinazolin‐4‐one) highly active against M21 cells (IC50 about 0.033 μM). Treatment of CH27 or HSC‐3 cells with MJ65–70 resulted in significant mitotic arrest accompanied by increasing multiple asters of microtubules. JNK protein expression was involved in the MJ65–70‐induced CH27 and M21 cell death. Consistent with the cell cycle arrest at G2/M phase, marked increases in cyclin B1 and Bcl‐2 phosphorylation were also observed, after treatment with MJ65–70.Conclusions and ImplicationMJ65–70 are dual‐targeted, tubulin‐ and JNK‐binding, anti‐cancer agents and induce cancer cell death through up‐regulation of JNK and interfering in the dynamics of tubulin. Our work provides a new strategy and mechanism for developing dual‐targeted anti‐cancer drugs, contributing to clinical anti‐cancer drug discovery and application.
• Lopez, Simon E.; Rosales, Monica E.; Urdaneta, Neudo, Journal of Chemical Research, Miniprint, 2000, # 6, p. 716 - 726
  作者：Lopez, Simon E.、Rosales, Monica E.、Urdaneta, Neudo、Godoy, M. Valentina、Charris, Jaime E.

  DOI：——

  日期：——