2-硝基-5-(1-哌啶)-苯甲酰胺 | 421558-77-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 2-硝基-5-(1-哌啶)-苯甲酰胺
• 英文名称: 2-nitro-5-(1-piperidino)-benzamide
• 英文别名: 2-nitro-5-(piperidin-1-yl)benzamide；2-nitro-5-piperidin-1-ylbenzamide
• CAS: 421558-77-2
• 化学式: C₁₂H₁₅N₃O₃
• 分子量: 249.269
• InChiKey: UPXUGZZQMDNPJD-UHFFFAOYSA-N

物化性质

• 沸点：
  424.2±35.0 °C(Predicted)
• 密度：
  1.296±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  92.2
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  2-硝基-5-(1-哌啶)-苯甲酰胺 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 生成 2-氨基-5-(哌啶-1-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
• 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 2-硝基-5-(1-哌啶)-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

• SYNTHESIS AND PRELIMINARY CYTOTOXIC AND ANTIFUNGAL EVALUATION OF SOME 6-N,N-DIALKYL 2-ARYL-4(3H)-QUINAZOLINONE DERIVATIVES
  作者：Simon E. Lopez、Monica E. Rosales、Carlos E. Canelon、Edgar A. Valverde、Rosa C. Narvaez、Jaime E. Charris、Fernando A Giannini、Ricardo D. Enriz、Mirta Carrasco、Susana Zacchino

  DOI：10.1515/hc.2001.7.5.473

  日期：2001.1

  new cytotoxic agents [13]. Their biological activity toward yeast, fi lamentous and dermatophyte fungi were also evaluated. Results and discussion The 2-aryl and alkyl 4(3//)-quinazolinones have been prepared by a variety of procedures, which include the classic cyclisation-dehydration of previously synthesized N-acyl anthranilic acid derivatives [14], reaction of ammonia with 4(3-oxazolin)-ones [15]

  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
• [EN] INDAZOLINONE COMPOSITIONS USEFUL AS KINASE INHIBITORS<br/>[FR] COMPOSITIONS INDAZOLINONES UTILES EN TANT QU'INHIBITEURS DES KINASES
  申请人：VERTEX PHARMA

  公开号：WO2004037814A1

  公开（公告）日：2004-05-06

  The present invention provides compounds of formula (I): These compounds, and pharmaceutically acceptable compositions thereof, are useful generally as kinase inhibitors, particularly as inhibitors of PRAK, GSK3, ERK2, CDK2, MK2, SRC, SYK, and Aurora-2. Accordingly, compounds and compositions of the invention are useful for treating or lessening the severity of a variety of disorders, including, but not limited to, heart disease, diabetes, Alzheimer's disease, immunodeficiency disorders, inflammatory diseases, allergic diseases, autoimmune diseases, destructive bone disorders such as osteoporosis, proliferative disorders, infectious diseases and viral diseases.

  本发明提供了式(I)的化合物：这些化合物及其药学上可接受的组合物通常用作激酶抑制剂，特别是作为PRAK、GSK3、ERK2、CDK2、MK2、SRC、SYK和Aurora-2的抑制剂。因此，本发明的化合物和组合物可用于治疗或减轻各种疾病的严重程度，包括但不限于心脏病、糖尿病、阿尔茨海默病、免疫缺陷病、炎症性疾病、过敏性疾病、自身免疫疾病、破坏性骨疾病如骨质疏松症、增生性疾病、传染病和病毒性疾病。
• Indazolinone compositions useful as kinase inhibitors
  申请人：——

  公开号：US20040167121A1

  公开（公告）日：2004-08-26

  The present invention provides compounds of formula I: 1 These compounds, and pharmaceutically acceptable compositions thereof, are useful generally as kinase inhibitors, particularly as inhibitors of PRAK, GSK3, ERK2, CDK2, MK2, SRC, SYK, and Aurora-2. Accordingly, compounds and compositions of the invention are useful for treating or lessening the severity of a variety of disorders, including, but not limited to, heart disease, diabetes, Alzheimer's disease, immunodeficiency disorders, inflammatory diseases, allergic diseases, autoimmune diseases, destructive bone disorders such as osteoporosis, proliferative disorders, infectious diseases and viral diseases.

  本发明提供了I式化合物：1这些化合物及其药学上可接受的组合物通常用作激酶抑制剂，特别是作为PRAK、GSK3、ERK2、CDK2、MK2、SRC、SYK和Aurora-2的抑制剂。因此，本发明的化合物和组合物可用于治疗或减轻各种疾病的严重程度，包括但不限于心脏病、糖尿病、阿尔茨海默病、免疫缺陷病、炎症性疾病、过敏性疾病、自身免疫疾病、破坏性骨疾病如骨质疏松症、增生性疾病、传染病和病毒性疾病。
• INDAZOLINONE COMPOSITIONS USEFUL AS KINASE INHIBITORS
  申请人：Aronov Alex

  公开号：US20090048250A1

  公开（公告）日：2009-02-19

  The present invention provides compounds of formula I: These compounds, and pharmaceutically acceptable compositions thereof, are useful generally as kinase inhibitors, particularly as inhibitors of PRAK, GSK3, ERK2, CDK2, MK2, SRC, SYK, and Aurora-2. Accordingly, compounds and compositions of the invention are useful for treating or lessening the severity of a variety of disorders, including, but not limited to, heart disease, diabetes, Alzheimer's disease, immunodeficiency disorders, inflammatory diseases, allergic diseases, autoimmune diseases, destructive bone disorders such as osteoporosis, proliferative disorders, infectious diseases and viral diseases.

  本发明提供了I式化合物：这些化合物及其药学上可接受的组合物通常用作激酶抑制剂，特别是作为PRAK、GSK3、ERK2、CDK2、MK2、SRC、SYK和Aurora-2的抑制剂。因此，本发明的化合物和组合物可用于治疗或减轻各种疾病的严重程度，包括但不限于心脏疾病、糖尿病、阿尔茨海默病、免疫缺陷病、炎症性疾病、过敏性疾病、自身免疫性疾病、破坏性骨疾病（如骨质疏松症）、增生性疾病、传染病和病毒性疾病。
• 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.