5-吗啉-4-基-2-硝基苯甲酰胺 | 404009-38-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: 5-吗啉-4-基-2-硝基苯甲酰胺
• 英文名称: 2-nitro-5-(1-morpholino)-benzamide
• 英文别名: 5-morpholino-2-nitrobenzamide；5-morpholin-4-yl-2-nitro-benzamide；5-Morpholino-2-nitrobenzenecarboxamide；5-morpholin-4-yl-2-nitrobenzamide
• CAS: 404009-38-7
• 化学式: C₁₁H₁₃N₃O₄
• 分子量: 251.242
• InChiKey: GRAJYPRJHNYASS-UHFFFAOYSA-N

物化性质

• 熔点：
  280-282°C

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  5-吗啉-4-基-2-硝基苯甲酰胺 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、275.79 kPa 条件下， 反应 3.0h， 以98%的产率得到2-氨基-5-(吗啉-4-基)苯甲酰胺
  参考文献：
  名称：

  一些 6-N,N-二烷基 2-芳基-4(3H)-喹唑啉酮衍生物的合成和初步细胞毒性和抗真菌评价

  摘要：

  制备了一些在 6 位带有环状氨基的新 2-芳基-4-喹唑啉酮衍生物，并报告了它们的初步细胞毒性和抗真菌性评价。它们都显示出中等的细胞毒性，这表明不仅 NI -C2 键的氧化态是这种生物活性的关键因素。这些喹唑啉酮针对几种酵母菌、丝状真菌和皮肤癣菌进行了测试，结果表明它们都没有活性 引言 多年来，4(3//)-喹唑啉酮核与具有广泛药理活性的多种结构有关，包括镇痛、麻醉剂、抗菌剂、抗癌剂、抗惊厥剂、抗高血压剂、抗炎剂、抗病毒剂、抗疟剂和抗寄生虫剂、支气管扩张剂、利尿剂、肌肉松弛剂、抗镇静剂和最近，在设计用于治疗勃起功能障碍的新型磷酸二酯酶 5 (PDE5) 抑制剂和胸苷酸合酶 (TS) 酶的一些抑制剂 [1-8]干扰微管系统的细胞毒性-抗肿瘤药物已经出现 这种化合物的特别重要的例子是 2-芳基-4-喹诺酮 1 和 2-芳基-萘啶-4-酮 2，两者都具有相对简单的骨架 [9 -12]，这些发现旨在让我们制备一些

  DOI：

  10.1515/hc.2001.7.5.473
• 作为产物：
  描述：

  间氟苯甲酸 在 氯化亚砜 、 硫酸 、 氨 、 硝酸 、 potassium carbonate 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 4.0h， 生成 5-吗啉-4-基-2-硝基苯甲酰胺
  参考文献：
  名称：

  2-((3,5-二硝基苯甲基)硫代)喹唑啉酮：由脱氮黄素 (F420) 依赖性硝基还原酶 (Ddn) 激活的有效抗分枝杆菌药物

  摘要：

  交换先前合成但尚未公开的 5-cyano-4-(methylthio)-2-arylpyrimidin-6-ones 4 的 2 和4位取代基、闭环和进一步优化导致鉴定出有效的抗结核药物 2-硫代喹唑啉酮26。结构-活性关系（SAR）研究表明，两个间硝基取代基在抗结核活性中发挥着至关重要的作用，而在喹唑啉酮核心上引入极性取代基可以减少牛血清白蛋白（BSA）的结合（ 63c，63d）。虽然大多数测试的喹唑啉酮类化合物没有表现出针对 MRC-5 的细胞毒性，但通过 Ames 测试发现最有效的化合物26具有诱变性。该类似物对结核分枝杆菌胸苷酸激酶（3-氰基吡啶酮的靶标，位于当前类似物的基础上）表现出中等的抑制效力，表明本发明的S-取代的硫代喹唑啉酮的全细胞抗分枝杆菌活性可能是由于调节替代或额外目标。观察到受辅因子 F 420生物合成 ( fbiC )、辅因子还原 ( fgd ) 或去氮黄素依赖性硝基还原酶活性

  DOI：

  10.1021/acs.jmedchem.0c01374

文献信息

• [EN] NOVEL ANTI-INFLAMMATORY AGENTS<br/>[FR] NOUVEAUX AGENTS ANTI-INFLAMMATOIRES
  申请人：RESVERLOGIX CORP

  公开号：WO2010123975A1

  公开（公告）日：2010-10-28

  Disclosed are methods of regulating interleukin-6 (IL-6) and/or vascular cell adhesion molecule-1 (VCAM-1) and methods of treating and/or preventing cardiovascular and inflammatory diseases and related disease states, such as, for example, atherosclerosis, asthma, arthritis, cancer, multiple sclerosis, psoriasis, and inflammatory bowel diseases, and autoimmune disease(s) by administering a naturally occurring or synthetic quinazolone derivative. The invention provides novel synthetic quinazolone compounds, as well as pharmaceutical compositions comprising those compounds.

  揭示了调节白细胞介素-6（IL-6）和/或血管细胞粘附分子-1（VCAM-1）的方法，以及治疗和/或预防心血管和炎症性疾病及相关疾病状态的方法，例如动脉粥样硬化、哮喘、关节炎、癌症、多发性硬化、牛皮癣和炎症性肠病以及自身免疫疾病，通过给予天然存在或合成的喹唑啉衍生物。该发明提供了新颖的合成喹唑啉化合物，以及包含这些化合物的药物组合物。
• Materials and methods to potentiate cancer treatment
  申请人：——

  公开号：US20020165218A1

  公开（公告）日：2002-11-07

  Compounds that inhibit DNA-dependent protein kinase, compositions comprising the compounds, methods to inhibit the DNA-PK biological activity, methods to sensitize cells the agents that cause DNA lesions, and methods to potentiate cancer treatment are disclosed.

  抑制DNA依赖性蛋白激酶的化合物，包含这些化合物的组合物，抑制DNA-PK生物活性的方法，使细胞对引起DNA损伤的药物敏感的方法，以及增强癌症治疗的方法被披露。
• NOVEL ANTI-INFLAMMATORY AGENTS
  申请人：Hansen Henrik C.

  公开号：US20120059002A1

  公开（公告）日：2012-03-08

  Disclosed are methods of regulating interleukin-6 (IL-6) and/or vascular cell adhesion molecule-1 (VCAM-1) and methods of treating and/or preventing cardiovascular and inflammatory diseases and related disease states, such as, for example, atherosclerosis, asthma, arthritis, cancer, multiple sclerosis, psoriasis, and inflammatory bowel diseases, and autoimmune disease(s) by administering a naturally occurring or synthetic quinazolone derivative. The invention provides novel synthetic quinazolone compounds, as well as pharmaceutical compositions comprising those compounds.

  本发明涉及调节白细胞介素-6（IL-6）和/或血管细胞黏附分子-1（VCAM-1）的方法，以及治疗和/或预防心血管和炎症性疾病及相关疾病状态的方法，例如动脉粥样硬化、哮喘、关节炎、癌症、多发性硬化、牛皮癣和炎性肠病等自身免疫疾病，通过给予天然或合成的喹唑啉衍生物。该发明提供了新型合成喹唑啉化合物，以及包含这些化合物的药物组合物。
• 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.
• 6-Alkylamino- and 2,3-Dihydro-3‘-methoxy-2-phenyl-4-quinazolinones and Related Compounds:  Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization
  作者：Mann-Jen Hour、Li-Jiau Huang、Sheng-Chu Kuo、Yi Xia、Kenneth Bastow、Yuka Nakanishi、Ernest Hamel、Kuo-Hsiung Lee

  DOI：10.1021/jm000151c

  日期：2000.11.1

  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.