N-[2-(氯乙酰基)苯基]-乙酰胺 | 68095-22-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: N-[2-(氯乙酰基)苯基]-乙酰胺
• 英文名称: N-(2-(2-chloroacetyl)phenyl)acetamide
• 英文别名: acetic acid-(2-chloroacetyl-anilide)；2-Chlor-1-(2-acetamino-phenyl)-aethanon-(1)；Essigsaeure-(2-chloracetyl-anilid)；2-Acetamino-phenacylchlorid；o-chloroacetoacetanilide；2-(Acetylamino)-α-chloracetophenon；Acetamide, N-[2-(chloroacetyl)phenyl]-；N-[2-(2-chloroacetyl)phenyl]acetamide
• CAS: 68095-22-7
• 化学式: C₁₀H₁₀ClNO₂
• 分子量: 211.648
• InChiKey: YFMSVNDUFQTTBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-[2-(氯乙酰基)苯基]-乙酰胺 在 氢氧化钾 、 乙醇 作用下， 生成 1H,1H'-2,2'-Biindolylidene-3,3'-dione
  参考文献：
  名称：

  柏林衍生产品中的4,6-二氨基-1,3-二乙酰基-苯甲醚和塞纳河上游。苯并双吡啶。（30. MitteilungüberStickstoff-Heterocyclen）

  摘要：

  DOI：

  10.1002/hlca.193702001130
• 作为产物：
  描述：

  2-(2-Chloroethanimidoyl)aniline 在 盐酸 作用下， 以 水 为溶剂， 反应 1.0h， 生成 N-[2-(氯乙酰基)苯基]-乙酰胺
  参考文献：
  名称：

  Identification, Design and Biological Evaluation of Heterocyclic Quinolones Targeting Plasmodium falciparum Type II NADH:Quinone Oxidoreductase (PfNDH2)

  摘要：

  Following a program undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a novel enzyme target within the malaria parasite Plasmodium falciparum, hit to lead optimization led to identification of CK-2-68, a molecule suitable for further development. In order to reduce ClogP and improve solubility of CK-2-68 incorporation of a variety of heterocycles, within the side chain of the quinolone core, was carried out, and this approach led to a lead compound SL-2-25 (8b). 8b has IC(50)s in the nanomolar range versus both the enzyme and whole cell P. falciparum (IC50 = 15 nM PfNDH2; IC50 = 54 nM (3D7 strain of P. falciparum) with notable oral activity of ED50/ED90 of 1.87/4.72 mg/kg versus Plasmodium berghei (NS Strain) in a murine model of malaria when formulated as a phosphate salt. Analogues in this series also demonstrate nanomolar activity against the bc(1) complex of P. falciparum providing the potential added benefit of a dual mechanism of action. The potent oral activity of 2-pyridyl quinolones underlines the potential of this template for further lead optimization studies.

  DOI：

  10.1021/jm201184h

文献信息

• Probing the Azaaurone Scaffold against the Hepatic and Erythrocytic Stages of Malaria Parasites
  作者：Marta P. Carrasco、Marta Machado、Lídia Gonçalves、Moni Sharma、Jiri Gut、Amanda K. Lukens、Dyann F. Wirth、Vânia André、Maria Teresa Duarte、Rita C. Guedes、Daniel J. V. A. dos Santos、Philip J. Rosenthal、Ralph Mazitschek、Miguel Prudêncio、Rui Moreira

  DOI：10.1002/cmdc.201600327

  日期：2016.10.6

  potential of azaaurones as dual‐stage antimalarial agents was investigated by assessing the effect of a small library of azaaurones on the inhibition of liver and intraerythrocytic lifecycle stages of the malaria parasite. The whole series was screened against the blood stage of a chloroquine‐resistant Plasmodium falciparum strain and the liver stage of P. berghei, yielding compounds with dual‐stage activity

  通过评估一个小图书馆的氮杂金龙素对抑制疟原虫的肝脏和红细胞生命周期阶段的作用，研究了氮杂金龙素作为双阶段抗疟药的潜力。针对抗氯喹疟原虫恶性疟原虫的血液阶段和伯氏疟原虫的肝阶段筛选了整个系列，产生了具有双阶段活性和亚微摩尔效价的抗红细胞寄生虫的化合物。使用基于恶性疟原虫Dd2- Sc的表型分析法对转基因寄生虫进行研究表达酵母二氢乳清酸脱氢酶（DHODH）的DHODH品系显示，其中的一种氮金龙酮衍生物具有抑制寄生虫线粒体电子传输链的潜能。在全球范围内寻找新的治疗疟疾的紧迫性，尤其是针对尚未开发的肝阶段，以及与氮杂金刚酮的化学易处理性相关的疟疾，都需要进一步发展这种化学型。总体而言，这些结果强调了氮杂紫罗兰的化学型是双阶段抗疟药的有希望的支架。
• Azaaurones as Potent Antimycobacterial Agents Active against MDR‐ and XDR‐TB
  作者：André Campaniço、Marta P. Carrasco、Mathew Njoroge、Ronnett Seldon、Kelly Chibale、João Perdigão、Isabel Portugal、Digby F. Warner、Rui Moreira、Francisca Lopes

  DOI：10.1002/cmdc.201900289

  日期：2019.8.20

  isosteric counterparts, azaaurones and N-acetylazaaurones, against Mycobacterium tuberculosis. Aurones were found to be inactive at 20 μm, whereas azaaurones and N-acetylazaaurones emerged as the most potent compounds, with nine derivatives displaying MIC99 values ranging from 0.4 to 2.0 μm. In addition, several N-acetylazaaurones were found to be active against multidrug-resistant (MDR) and extensively drug-resistant

  在此，我们报告了针对结核分枝杆菌的一个小型金黄色素及其等排性对映体，氮卓酮和N-乙酰基氮卓酮的文库的筛选。发现Aurones在20μm处无活性，而氮杂Aauaurones和N-乙酰基氮杂Aauaurones则是最有效的化合物，其中九种衍生物的MIC99值在0.4至2.0μm之间。另外，发现几种N-乙酰氮杂金龙酮对多药耐药（MDR）和广泛耐药（XDR）临床结核分枝杆菌具有活性。这些化合物的抗分枝杆菌的作用机理尚待确定。但是，一项初步的机理研究证实，它们不会抑制分枝杆菌细胞色素bc1复合物。此外，微粒体的代谢稳定性和代谢物鉴定研究表明，N-乙酰基氮杂金龙酮被脱乙酰化为其对应的氮杂金龙酮。总体而言，这些结果表明，氮金龙酮及其N-乙酰基对应物代表了能够抑制结核分枝杆菌生长的化学型工具箱中的一个新条目。
• Copper‐Catalyzed Acylhalogenation of 3‐Methylanthranils with Acid Halides: Synthesis of <i>N</i> ‐(2‐(2‐Haloyl)phenyl)amides
  作者：Baihui Liang、Tingting Wen、Guanrui Chen、Zechun Cai、Jucai Xu、Xiuwen Chen、Zhongzhi Zhu

  DOI：10.1002/adsc.202200547

  日期：2022.9.20

  A copper-catalyzed acylhalogenation reaction of 3-methylanthranils with acid halides, which utilizes the acyl halide as both the acylating and halogenating source, is described. This process involves N−O/C−H/C−X bond cleavages and C−N/C−X bond formations to furnish N-(2-(2-haloyl)phenyl)amides. Furthermore, this difunctional conversion using the N−O bond and oxygen as oxidants displays good tolerance

  描述了利用酰卤作为酰化和卤化源的 3-甲基邻氨基苯酚与酰卤的铜催化酰卤化反应。该过程涉及 N-O/C-H/C-X 键断裂和 C-N/C-X 键形成，以提供N- (2-(2-卤酰基)苯基)酰胺。此外，这种使用 N-O 键和氧作为氧化剂的双功能转化对不同的官能团表现出良好的耐受性。
• Structural Optimization of Antimycobacterial Azaaurones Towards Improved Solubility and Metabolic Stability
  作者：André Campaniço、Shrika G. Harjivan、Elisabete Freitas、Marco Serafini、M. Manuela Gaspar、Rita Capela、Pedro Gomes、Audrey Jordaan、Ana M. Madureira、Vânia André、Andreia B. Silva、M. Teresa Duarte、Isabel Portugal、João Perdigão、Rui Moreira、Digby F. Warner、Francisca Lopes

  DOI：10.1002/cmdc.202300410

  日期：2023.12.14

  Azaaurones are potent agents against M.tb. This new family of compounds improved the overall metabolic stability and solubility of the scaffold, with 24 compounds with submicromolar activities and 4 compounds in the nanomolar range. Furthermore, all tested derivatives were equipotent among susceptible and drug-resistant tuberculosis, with activity against multidrug-resistant (MDR) and extensively drug-resistant

  Azaaurones 是对抗M.tb 的有效药物。这个新的化合物家族提高了支架的整体代谢稳定性和溶解度，其中 24 种化合物具有亚微摩尔活性，4 种化合物在纳摩尔范围内。此外，所有测试的衍生物在易感和耐药结核病中均具有同等效力，对多重耐药（MDR）和广泛耐药（XDR）临床结核分枝杆菌分离株具有活性。
• New azaaurone derivatives as potential multitarget agents in HIV‐TB coinfection
  作者：Debora I. Leite、Andre Campaniço、Pedro A. G. Costa、Isadora A. Correa、Luciana J. da Costa、Monica M. Bastos、Rui Moreira、Francisca Lopes、Audrey Jordaan、Digby F. Warner、Nubia Boechat

  DOI：10.1002/ardp.202300560

  日期：2024.2

  work aimed to obtain new multitarget HIV-TB agents, with the goal of optimizing treatments and preventing this coinfection. These compounds incorporate the structural features of azaaurones as anti-Mtb and zidovudine (AZT) as the antiretroviral moiety. The azaaurone scaffold displayed submicromolar activities against Mtb, and AZT is a potent antiretroviral drug. Six derivatives were synthetically generated

  由结核分枝杆菌( MTb ) 引起的结核病 (TB) 是人类免疫缺陷病毒 (HIV) 感染者死亡的主要原因。目前尚无双靶点药物可同时治疗这两种感染。这项工作旨在获得新的多靶点 HIV-TB 药物，以优化治疗并预防这种双重感染。这些化合物结合了作为抗MTb 药物的氮杂黄酮和作为抗逆转录病毒部分的齐多夫定 (AZT) 的结构特征。氮杂黄酮支架显示出针对MTb 的亚微摩尔活性，AZT 是一种有效的抗逆转录病毒药物。合成产生了六种衍生物，并针对两种感染因子评估了五种衍生物。在感染 HIV-1 的 MT-4 细胞和内源性 HIV-1 逆转录酶 (RT) 活性中进行抗 HIV 活性评估。 H37Rv 菌株用于抗MTb评估。大多数化合物显示出有效的抗结核活性和中等的抗艾滋病毒活性。 ( E ) -12在 HIV-1 感染的 T 淋巴细胞中表现出良好的多靶点特性，MIC 90为 2.82 µM，IC 50为