2-chloro-N-methyl-5-nitrobenzenesulfonamide | 89793-16-8

• 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: 2-chloro-N-methyl-5-nitrobenzenesulfonamide
• 英文别名: 2-chloro-N-methyl-5-nitrobenzene-1-sulfonamide
• CAS: 89793-16-8
• 化学式: C₇H₇ClN₂O₄S
• mdl: MFCD11124851
• 分子量: 250.663
• InChiKey: HQWDUSKGEOZAEL-UHFFFAOYSA-N

物化性质

• 沸点：
  398.6±52.0 °C(Predicted)
• 密度：
  1.530±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-N-methyl-5-nitrobenzenesulfonamide 在 sodium hydroxide 、 尿素 作用下， 生成 3-Nitro-6-hydroxy-benzolsulfonsaeure-methylamid
  参考文献：
  名称：

  Lavrishchev,V.A. et al., Journal of general chemistry of the USSR, 1960, vol. 30, p. 3037 - 3044

  摘要：

  DOI：
• 作为产物：
  描述：

  2-氯-5-硝基苯磺酸 在 氯化亚砜 、 N,N-二甲基甲酰胺 、 potassium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 2-chloro-N-methyl-5-nitrobenzenesulfonamide
  参考文献：
  名称：

  Development of Benzenesulfonamide Derivatives as Potent Glutathione Transferase Omega-1 Inhibitors

  摘要：

  Glutathione transferase omega-1 (GSTO1-1) is an enzyme whose function supports the activation of interleukin (IL)-1 beta and IL-18 that are implicated in a variety of inflammatory disease states for which small-molecule inhibitors are sought. The potent reactivity of the active-site cysteine has resulted in reported inhibitors that act by covalent labeling. In this study, structure-activity relationship (SAR) elaboration of the reported GSTO1-1 inhibitor C1-27 was undertaken. Compounds were evaluated for inhibitory activity toward purified recombinant GSTO1-1 and for indicators of target engagement in cell-based assays. As covalent inhibitors, the k(inact)/K-I values of selected compounds were determined, as well as in vivo pharmacokinetics analysis. Cocrystal structures of key novel compounds in complex with GSTO1-1 were also solved. This study represents the first application of a biochemical assay for GSTO1-1 to determine k(inact)/K-I values for tested inhibitors and the most extensive set of cell-based data for a GSTO1-1 inhibitor SAR series reported to date. Our research culminated in the discovery of 25, which we propose as the preferred biochemical tool to interrogate cellular responses to GSTO1-1 inhibition.

  DOI：

  10.1021/acs.jmedchem.9b01391

文献信息

• Design, Synthesis, <i>In Vitro</i> and <i>In Vivo</i> Characterization of Selective NKCC1 Inhibitors for the Treatment of Core Symptoms in Down Syndrome
  作者：Marco Borgogno、Annalisa Savardi、Jacopo Manigrasso、Alessandra Turci、Corinne Portioli、Giuliana Ottonello、Sine Mandrup Bertozzi、Andrea Armirotti、Andrea Contestabile、Laura Cancedda、Marco De Vivo

  DOI：10.1021/acs.jmedchem.1c00603

  日期：2021.7.22

  Intracellular chloride concentration [Cl–]i is defective in several neurological disorders. In neurons, [Cl–]i is mainly regulated by the action of the Na+–K+–Cl– importer NKCC1 and the K+–Cl– exporter KCC2. Recently, we have reported the discovery of ARN23746 as the lead candidate of a novel class of selective inhibitors of NKCC1. Importantly, ARN23746 is able to rescue core symptoms of Down syndrome

  细胞内氯化物浓度 [Cl – ] i在几种神经系统疾病中存在缺陷。在神经元中，[Cl – ] i主要受 Na + –K + –Cl –输入端 NKCC1 和 K + –Cl –输出端 KCC2的作用调节。最近，我们报道了发现ARN23746作为一类新型 NKCC1 选择性抑制剂的主要候选物。重要的是，ARN23746能够在小鼠模型中挽救唐氏综合症 (DS) 和自闭症的核心症状。在这里，我们描述了这类化学选择性 NKCC1 抑制剂的发现和广泛表征，重点是ARN23746和其他有前途的衍生物。特别是，我们提出了化合物40 ( ARN24092 ) 作为在 DS 小鼠模型中具有体内功效的备用/后续先导。这些结果进一步加强了这类新化合物在治疗以 NKCC1/KCC2 表达比率缺陷为特征的脑部疾病的核心症状方面的潜力。
• [EN] MODULATORS OF INTRACELLULAR CHLORIDE CONCENTRATION<br/>[FR] MODULATEURS DE LA CONCENTRATION DE CHLORURE INTRACELLULAIRE
  申请人：FONDAZIONE ST ITALIANO TECNOLOGIA

  公开号：WO2020202072A1

  公开（公告）日：2020-10-08

  The present invention relates to a compound of Formula la, lb and Ic, (Formula Ia) a pharmaceutical composition comprising the same and their use in the treatment or prevention of pathological conditions associated to depolarizing GABAergic transmission including, for example, Down syndrome and autism.

  本发明涉及化合物Ia、Ib和Ic的公式（公式Ia），包括相同的药物组合物以及它们在治疗或预防与去极化GABA能传导相关的病理条件中的用途，例如唐氏综合征和自闭症。
• New approach to the synthesis of 3-amino-1,2-benzothiazine 1,1-dioxides
  作者：A. G. Nemazanyi、Yu. M. Volovenko、V. V. Neshchadimenko、F. S. Babichev

  DOI：10.1007/bf00473949

  日期：1992.2
• AQUAPORIN MODULATORS AND METHODS OF USING THEM FOR THE TREATMENT OF EDEMA AND FLUID IMBALANCE
  申请人：The Arizona Board of Regents on behalf of the University of Arizona

  公开号：EP2086329B1

  公开（公告）日：2014-07-23
• MODULATORS OF INTRACELLULAR CHLORIDE CONCENTRATION
  申请人：Fondazione Istituto Italiano di Tecnologia

  公开号：EP3947345A1

  公开（公告）日：2022-02-09