5-氨基-2-氯-N,N-二甲基苯磺酰胺 | 10475-06-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-氨基-2-氯-N,N-二甲基苯磺酰胺
• 英文名称: 5-amino-2-chloro-N,N-dimethylbenzenesulfonamide
• 英文别名: 5-Amino-2-chloro-N,N-dimethyl-benzenesulfonamide
• CAS: 10475-06-6
• 化学式: C₈H₁₁ClN₂O₂S
• mdl: MFCD02700603
• 分子量: 234.707
• InChiKey: ODCHLWPLEOVWHX-UHFFFAOYSA-N

物化性质

• 熔点：
  124.0-125.5 °C
• 沸点：
  401.9±55.0 °C(Predicted)
• 密度：
  1.387±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 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：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2935009090

反应信息

• 作为反应物：
  描述：

  5-氨基-2-氯-N,N-二甲基苯磺酰胺 在 氢溴酸 、 sodium nitrite 、 copper(I) bromide 作用下， 以 水 、 乙腈 为溶剂， 以75%的产率得到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 、 氯化铵 、 三乙胺 、 N,N-二甲基甲酰胺 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 5-氨基-2-氯-N,N-二甲基苯磺酰胺
  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

• Methods for inhibiting protein kinases
  申请人：Guzi J. Timothy

  公开号：US20070082900A1

  公开（公告）日：2007-04-12

  The present invention provides methods for inhibiting protein kinases selected from the group consisting of AKT, Checkpoint kinase, Aurora kinase, Pim kinases, and tyrosine kinase using pyrazolo[1,5-a]pyrimidine compounds and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with protein kinases using such compounds.

  本发明提供了使用吡唑并[1,5-a]嘧啶化合物抑制选自AKT、检查点激酶、极光激酶、Pim激酶和酪氨酸激酶的蛋白激酶的方法，以及使用这些化合物治疗、预防、抑制或改善与蛋白激酶相关的一种或多种疾病的方法。
• Structure-Based Design of <i>N</i>-(5-Phenylthiazol-2-yl)acrylamides as Novel and Potent Glutathione S-Transferase Omega 1 Inhibitors
  作者：Weiyang Dai、Soma Samanta、Ding Xue、Elyse M. Petrunak、Jeanne A. Stuckey、Yanyan Han、Duxin Sun、Yong Wu、Nouri Neamati

  DOI：10.1021/acs.jmedchem.8b01960

  日期：2019.3.28

  Using reported glutathione S-transferase omega 1 (GSTO1-1) cocrystal structures, we designed and synthesized acrylamide-containing compounds that covalently bind to Cys32 on the catalytic site. Starting from a thiazole derivative 10 (GSTO1-1 IC50 = 0.6 μM), compound 18 was synthesized and cocrystallized with GSTO1. Modification on the amide moiety of hit compound 10 significantly increased the GSTO1-1

  使用报道的谷胱甘肽 S-转移酶 omega 1 (GSTO1-1) 共晶结构，我们设计并合成了与催化位点上的 Cys32 共价结合的含丙烯酰胺化合物。从噻唑衍生物 10 (GSTO1-1 IC50 = 0.6 μM) 开始，合成化合物 18 并与 GSTO1 共结晶。对命中化合物 10 的酰胺部分的修饰显着增加了 GSTO1-1 抑制效力。我们解决了带有与 GSTO1 结合的酰胺侧链的新衍生物 37 和 44 的共晶结构。与 18 相比，这些新结构显示了抑制剂 37 和 44 的苯基噻唑核心的重新定向。在 GSTO1:44 的共晶结构的指导下，设计了类似物 49，从而产生了最有效的 GSTO1-1 抑制剂（IC50 = 0.22 ± 0.02 nM) 迄今为止已知。
• 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。