N-(2-bromo-4-sulfamoylphenyl)-2-chloroacetamide | 53297-86-2

• 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: N-(2-bromo-4-sulfamoylphenyl)-2-chloroacetamide
• 英文别名: 2-Chloro-N-(2-bromo-4-sulphamoylphenyl)-acetamide
• CAS: 53297-86-2
• 化学式: C₈H₈BrClN₂O₃S
• 分子量: 327.586
• InChiKey: GEGXNWZYNFWKKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-bromo-4-sulfamoylphenyl)-2-chloroacetamide 在 苯胺 作用下， 生成 2-Phenylamino-N-(2-bromo-4-sulphamoylphenyl)-acetamide
  参考文献：
  名称：

  Sulphamoylphenyl-imidazolidinones

  摘要：

  通过将N-磺胺基苯基取代的α-氨基乙酰胺与甲醛或碳酸的活性衍生物环化，或者通过将N-卤磺酰基苯基取代的咪唑烷酮与氨反应，制备具有有用抗癫痫活性的N-磺胺基苯基取代的咪唑烷酮。

  公开号：

  US03963706A1
• 作为产物：
  描述：

  4-amino-3-bromo-benzenesulfonamide 、 氯乙酰氯 反应 1.0h， 以to yield 20.5 g white needles, m.p. 174°-175°的产率得到N-(2-bromo-4-sulfamoylphenyl)-2-chloroacetamide
  参考文献：
  名称：

  Sulphamoylphenyl-imidazolidinones

  摘要：

  具有有用的抗癫痫活性的N-磺酰基苯基取代咪唑啉-4-酮通过将N-磺酰基苯基取代的α-氨基乙酰胺与甲醛或碳酸的反应性衍生物环化，或通过将N-卤代磺酰基苯基取代的咪唑啉-4-酮与氨反应制备。

  公开号：

  US03963706A1

文献信息

• Arylazolyl(azinyl)thioacetanilides: Part 19: Discovery of Novel Substituted Imidazo[4,5-b]pyridin-2-ylthioacetanilides as Potent HIV NNRTIs Via a Structure-based Bioisosterism Approach
  作者：Xiao Li、Boshi Huang、Zhongxia Zhou、Ping Gao、Christophe Pannecouque、Dirk Daelemans、Erik De Clercq、Peng Zhan、Xinyong Liu

  DOI：10.1111/cbdd.12751

  日期：2016.8

  5‐b]pyridin‐2‐ylthioacetanilides were designed, synthesized, and evaluated for their antiviral activities through combining bioisosteric replacement and structure‐based drug design. Almost all of the title compounds displayed moderate to good activities against wild‐type (wt) HIV‐1 strain with EC50 values ranging from 0.059 to 1.41 μm in a cell‐based antiviral assay. Thereinto, compounds 12 and 13 were the most

  随着我们为发现有效的HIV-1 NNRTIs的不懈努力，我们设计了一系列新型咪唑并[4,5-b]吡啶-2--2-基硫代乙酰胺，并通过生物等排代用品和生物等效性评估了它们的抗病毒活性。基于结构的药物设计。几乎所有的标题化合物显示中等至对野生型（wt）HIV-1毒株具有EC良好活动50个值范围从0.059到1.41μ米在基于细胞的抗病毒测定。到其中，化合物12和13是最活跃2代的类似物具有的EC 50 0.059 0.073μ值米对抗WT HIV-1，分别，这比对照药物奈韦拉平更有效（EC 50 = 0.26μ米）并且与地拉呋啶（EC 50 = 0.038μ米）。另外，与奈韦拉平和依曲韦林相比，一种选择的化合物显示出显着的逆转录酶抑制活性。在本文的最后，详细讨论了初步的结构-活性关系（SAR）和分子建模研究，这可能为进一步优化提供有价值的见解。
• Dual Inhibitors of Brain Carbonic Anhydrases and Monoamine Oxidase-B Efficiently Protect against Amyloid-β-Induced Neuronal Toxicity, Oxidative Stress, and Mitochondrial Dysfunction
  作者：Simone Giovannuzzi、Daniel Chavarria、Gustavo Provensi、Manuela Leri、Monica Bucciantini、Simone Carradori、Alessandro Bonardi、Paola Gratteri、Fernanda Borges、Alessio Nocentini、Claudiu T. Supuran

  DOI：10.1021/acs.jmedchem.4c00045

  日期：2024.3.14

  We report here the first dual inhibitors of brain carbonic anhydrases (CAs) and monoamine oxidase-B (MAO-B) for the management of Alzheimer’s disease. Classical CA inhibitors (CAIs) such as methazolamide prevent amyloid-β-peptide (Aβ)-induced overproduction of reactive oxygen species (ROS) and mitochondrial dysfunction. MAO-B is also implicated in ROS production, cholinergic system disruption, and

  我们在这里报告了第一个用于治疗阿尔茨海默病的脑碳酸酐酶 (CA) 和单胺氧化酶 -B (MAO-B) 双重抑制剂。经典的 CA 抑制剂 (CAI)，例如醋甲唑胺，可防止淀粉样蛋白-β-肽 (Aβ) 诱导的活性氧 (ROS) 过量产生和线粒体功能障碍。 MAO-B 还与 ROS 产生、胆碱能系统破坏和淀粉样蛋白斑形成有关。在这项工作中，我们将香豆素和色酮类型的可逆 MAO-B 抑制剂与苯磺酰胺片段结合起来作为高效的 CAI。命中先导优化产生了一组重要的衍生物，对目标脑 CA（ K I范围为 0.1–90.0 nM）和 MAO-B（IC 50范围为 6.7– 32.6纳米）。进行计算研究以阐明构效关系并预测 ADMET 特性。在 SH-SY5Y 细胞模型中，最有效的多靶点化合物完全阻止了 Aβ 相关毒性、恢复了 ROS 形成并恢复了线粒体功能，其功效超越了单靶点药物的功效。
• 10.1016/j.ejmech.2024.116527
  作者：Hefny, Salma M.、El-Moselhy, Tarek F.、El-Din, Nabaweya、Ammara, Andrea、Angeli, Andrea、Ferraroni, Marta、El-Dessouki, Ahmed M.、Shaldam, Moataz A.、Yahya, Galal、Al-Karmalawy, Ahmed A.、Supuran, Claudiu T.、Tawfik, Haytham O.

  DOI：10.1016/j.ejmech.2024.116527

  日期：——

  describe the design and synthesis of novel aryl pyrimidine benzenesulfonamides , , , and as pazopanib analogues to explore new potent and selective inhibitors for the CA IX. All APBSs were examined in vitro for their promising inhibition activity against a small panel of hCAs (isoforms I, II, IX, and XII). The X-ray crystal structure of CA I in adduct with a representative analogue was solved. -, endowed

  在此，我们描述了新型芳基嘧啶苯磺酰胺 、 、 、 和 帕唑帕尼类似物的设计和合成，以探索新的有效且选择性的 CA IX 抑制剂。所有 APBS 均在体外检查了其对一小部分 hCA（亚型 I、II、IX 和 XII）的有希望的抑制活性。解析了 CA I 与代表性类似物加合物的 X 射线晶体结构。 - 具有最佳的 hCA IX 抑制功效和选择性，针对一小组不同的癌细胞系（SK-MEL-173、MDA-MB-231、A549、HCT-116 和 HeLa）进行了抗增殖活性评估，并且它展示了一位数 IC 值范围从 2.93 μM (MDA-MB-231) 到 5.86 μM (A549)。此外，还评估了化合物对 MDA-MB-231 癌细胞中缺氧诱导因子 (HIF-1α) 产生、细胞凋亡诱导和集落形成的影响。另外，在实体艾氏癌（SEC）动物模型中研究了 - 作为抗肿瘤剂的体内功效。为了了解所传递的
• Arylazolyl(azinyl)thioacetanilides. Part 16: Structure-based bioisosterism design, synthesis and biological evaluation of novel pyrimidinylthioacetanilides as potent HIV-1 inhibitors
  作者：Xiao Li、Xueyi Lu、Wenmin Chen、Huiqing Liu、Peng Zhan、Christophe Pannecouque、Jan Balzarini、Erik De Clercq、Xinyong Liu

  DOI：10.1016/j.bmc.2014.08.001

  日期：2014.10

  A series of novel pyrimidinylthioacetanilides were designed, synthesized, and evaluated for their biological activity as potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Most of the tested compounds were proved to be effective in inhibiting HIV-1 (IIIB) replication with EC50 ranging from 0.15 μM to 24.2 μM, thereinto compound 15 was the most active lead with favorable inhibitory activity against HIV-1 (IIIB) (EC50=0.15 μM, SI=684). Besides, compound 6 displayed moderate inhibition against the double-mutated HIV-1 strain (K103N/Y181C) (EC50=3.9 μM). Preliminary structure-activity relationships (SARs), structure-cytotoxicity relationships (SCRs) data, and molecular modeling studies were discussed as well, which may provide valuable insights for further optimizations.
• Arylazolyl(azinyl)thioacetanilides. Part 10: Design, synthesis and biological evaluation of novel substituted imidazopyridinylthioacetanilides as potent HIV-1 inhibitors
  作者：Xiao Li、Peng Zhan、Hong Liu、Dongyue Li、Liu Wang、Xuwang Chen、Huiqing Liu、Christophe Pannecouque、Jan Balzarini、Erik De Clercq、Xinyong Liu

  DOI：10.1016/j.bmc.2012.07.026

  日期：2012.9

  In continuation of our efforts toward the discovery of potent HIV-1 NNRTIs with novel structures, we have employed a scaffold hopping strategy to explore the chemically diversed space of bioactive compounds. The original arylazolylthioacetanilide platform was replaced with different imidazopyridinylthioacetanilide scaffolds to yield the optimal pharmacophore moieties in order to generate novel NNRTIs with desirable potency. Some of the new compounds proved able to inhibit HIV-1 replication in the low micromolar range. In particular, compound 5b16 displayed the most potent anti-HIV-1 activity (EC50 = 0.21 +/- 0.06 mu M), inhibiting HIV-1 IIIB replication in MT-4 cells more effectively than dideoxycytidine (EC50 = 1.4 +/- 0.1 mu M) and similarly with nevirapine (EC50 = 0.20 +/- 0.10 mu M). Preliminary structure-activity relationship (SAR) of the newly synthesized congeners is discussed, and molecular modeling study is performed to rationalize the SAR conclusions. (C) 2012 Elsevier Ltd. All rights reserved.