2-chloro-N,N-dimethyl-5-nitrobenzenesulfonamide | 10372-90-4

• 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,N-dimethyl-5-nitrobenzenesulfonamide
• 英文别名: 2-chloro-N,N-dimethyl-5-nitrobenzene-1-sulfonamide
• CAS: 10372-90-4
• 化学式: C₈H₉ClN₂O₄S
• mdl: MFCD09699506
• 分子量: 264.689
• InChiKey: OYTKZYRZJKFNSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  91.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-N,N-dimethyl-5-nitrobenzenesulfonamide 在 氢溴酸 、 氯化铵 、 锌 、 sodium nitrite 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 生成 5-bromo-2-chloro-N,N-dimethylbenzenesulfonamide
  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
• 作为产物：
  描述：

  2-氯-5-硝基苯磺酸 在 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 生成 2-chloro-N,N-dimethyl-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。
• Benzenesulfonamide derivatives and methods for their production
  申请人：Uniroyal Chemical Company, Inc.

  公开号：US05169430A1

  公开（公告）日：1992-12-08

  A compound having the structural formula ##STR1## wherein: R is hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 haloalkyl, formyl, C.sub.2 -C.sub.6 alkanoyl, C.sub.3 -C.sub.4 alkenyl or C.sub.3 -C.sub.4 alkynyl, or alkali metal; X is C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.8 alkoxy, cyano, or halogen; Y is hydrogen, halogen, or C.sub.1 -C.sub.4 dialkylamino; R.sup.1 is hydrogen, C.sub.1 -C.sub.8 straight chain or branched alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 alkenyl, C.sub.3 -C.sub.8 alkoxy or C.sub.3 -C.sub.8 hydroxyalkyl; R.sup.2 is hydrogen, C.sub.1 -C.sub.8 straight chain or branched alkyl, C.sub.3 -C.sub.8 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, halo substituted C.sub.3 -C.sub.8 alkenyl, C.sub.3 -C.sub.8 alkynyl, C.sub.1 -C.sub.4 alkoxy, hydroxy C.sub.1 -C.sub.4 alkyl, cyano C.sub.1 -C.sub.4 alkyl, 2,3-epoxypropyl, 2,2-dialkoxyethyl, alkoxyalkyl, phenyl, aralkyl, C.sub.1 -C.sub.4 acyl, C.sub.1 -C.sub.4 carbalkoxyalkyl, C.sub.1 -C.sub.4 carbalkoxyalkyl substituted by C.sub.1 -C.sub.4 alkyl, phenylmethyl or methylthioethyl, (1,3-dioxolan-2-yl)alkyl, dialkylaminoethyl, or tetrahydrofuranylmethyl; R.sup.3 is hydrogen, halogen or C.sub.1 -C.sub.4 alkyl; R.sup.4 is C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 haloalkyl; R.sup.1 and R.sup.2 taken together form a C.sub.3 -C.sub.8 membered heterocyclic ring containing one or more heteroatoms. In addition, processes and novel intermediate compounds that are useful for making the compound are set forth. A method for controlling weeds which comprises applying a herbicidally effective amount of the compound recited above is described. Also disclosed is a composition useful as an herbicide which includes a compound of this invention and a suitable carrier therefor.

  一种化合物具有结构式##STR1##其中：R是氢，C.sub.1-C.sub.4烷基，C.sub.1-C.sub.4卤代烷基，甲酰基，C.sub.2-C.sub.6烷酰基，C.sub.3-C.sub.4烯基或C.sub.3-C.sub.4炔基，或碱金属；X是C.sub.1-C.sub.4烷基，C.sub.1-C.sub.8烷氧基，氰基或卤素；Y是氢，卤素或C.sub.1-C.sub.4双烷基氨基；R.sup.1是氢，C.sub.1-C.sub.8直链或支链烷基，C.sub.3-C.sub.8环烷基，C.sub.3-C.sub.8烯基，C.sub.3-C.sub.8烷氧基或C.sub.3-C.sub.8羟基烷基；R.sup.2是氢，C.sub.1-C.sub.8直链或支链烷基，C.sub.3-C.sub.8烯基，C.sub.3-C.sub.8环烷基，卤代C.sub.3-C.sub.8烯基，C.sub.3-C.sub.8炔基，C.sub.1-C.sub.4烷氧基，羟基C.sub.1-C.sub.4烷基，氰基C.sub.1-C.sub.4烷基，2,3-环氧丙基，2,2-二烷氧基乙基，烷氧基烷基，苯基，芳基烷基，C.sub.1-C.sub.4酰基，C.sub.1-C.sub.4羧基烷氧基烷基，被C.sub.1-C.sub.4烷基取代的C.sub.1-C.sub.4羧基烷氧基烷基，苯基甲基或甲硫乙基，（1,3-二氧杂环戊烷-2-基）烷基，双烷基氨基乙基或四氢呋喃基甲基；R.sup.3是氢，卤素或C.sub.1-C.sub.4烷基；R.sup.4是C.sub.1-C.sub.4烷基或C.sub.1-C.sub.4卤代烷基；R.sup.1和R.sup.2共同形成一个含有一个或多个杂原子的C.sub.3-C.sub.8环的杂环。此外，还提供了制备该化合物有用的过程和新的中间体化合物。还描述了一种控制杂草的方法，该方法包括施用上述化合物的除草有效量。还揭示了一种用作除草剂的组合物，其中包括本发明的化合物和适当的载体。
• [EN] SUBSTRATE ADAPTOR INHIBITORS OF PRMT5 AND USES THEREOF<br/>[FR] INHIBITEURS D'ADAPTATEUR DE SUBSTRAT DE PRMT5 ET LEURS UTILISATIONS
  申请人：BROAD INST INC

  公开号：WO2022032144A1

  公开（公告）日：2022-02-10

  Provided herein are compounds that modulate PRTM5 activity. The compounds may inhibit the binding PRMT5 with a PRMT5 substrate adaptor. The compounds can modulate PRMT5 methyltransferase activity, modulate transcription of a gene regulated by PRMT5, modulate chromatin structure regulation, modulate cellular differentiation, and/or modulate mRNA splicing, e.g., by disrupting binding of PRMT5 with a PRMT5 substrate adaptor. Also provided are pharmaceutical compositions comprising the compounds, methods of modulating PRTM5 activity, and methods of treating disease (e.g., cancer) in a subject by administering a compound or composition described herein.

  本文提供了调节PRTM5活性的化合物。这些化合物可以抑制PRMT5与PRMT5底物适配器的结合。这些化合物可以调节PRMT5甲基转移酶活性，调节PRMT5调控的基因的转录，调节染色质结构调节，调节细胞分化，以及/或通过破坏PRMT5与PRMT5底物适配器的结合来调节mRNA剪接。此外，还提供了包含这些化合物的制药组合物，调节PRTM5活性的方法，以及通过给予本文所述的化合物或组合物治疗疾病（例如癌症）的方法。
• Pyrimidylbensulfonyl chloride compounds
  申请人：Uniroyal Chemical Company, Inc.

  公开号：US05486610A1

  公开（公告）日：1996-01-23

  Pyrimidinylbenzenesulfonyl chloride compounds of the formula ##STR1## wherein R is hydrogen, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 haloalkyl; X is C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.8 alkoxy, or halogen; Y is hydrogen or halogen; R.sup.3 is hydrogen, halogen or C.sub.1 -C.sub.4 alkyl; and R.sup.4 is C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 haloalkyl. The compounds are useful as intermediates in the preparation of herbicides.

  该化合物的化学式为##STR1##其中R为氢，C.sub.1-C.sub.4烷基或C.sub.1-C.sub.4卤代烷基; X为C.sub.1-C.sub.4烷基，C.sub.1-C.sub.8烷氧基或卤素; Y为氢或卤素; R.sup.3为氢，卤素或C.sub.1-C.sub.4烷基; R.sup.4为C.sub.1-C.sub.4烷基或C.sub.1-C.sub.4卤代烷基。这些化合物可用作除草剂制备中间体。