3-amino-5-chlorothiophene-2-sulfonamide | 508231-17-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 3-amino-5-chlorothiophene-2-sulfonamide
• 英文别名: 3-amino-5-chloro-thiophene-2-sulfonic acid amide
• CAS: 508231-17-2
• 化学式: C₄H₅ClN₂O₂S₂
• 分子量: 212.681
• InChiKey: RCMCEXCJNKTEDT-UHFFFAOYSA-N

物化性质

• 沸点：
  495.7±55.0 °C(Predicted)
• 密度：
  1.741±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,2-二氟乙酰氯 、 3-amino-5-chlorothiophene-2-sulfonamide 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以76%的产率得到5-chloro-3-(2,2-difluoroacetamido)thiophene-2-sulfonamide
  参考文献：
  名称：

  Development of Thiophenic Analogues of Benzothiadiazine Dioxides as New Powerful Potentiators of 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid (AMPA) Receptors

  摘要：

  On the basis of the results obtained in previous series of AMPA potentiators belonging to 3,4-dihydro-2H-benzo- and 3,4-dihydro-2H-pyrido-1,2,4-thiadiazine 1,1-dioxides, the present work focuses on the design of original isosteric 3,4-dihydro-2H-thieno-1,2,4-thiadiazine 1,1-dioxides. Owing to the sulfur position, three series of compounds were developed and their activity as AMPA potentiators was characterized. In each of the developed series, potent compounds were discovered. After screening the selected active compounds on a safety in vivo test, 6-chloro-4-ethyl-3,4-dihydro-2H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide (24) appeared as the most promising compound and was further evaluated. Its effects on long-term potentiation in vivo and on AMPA-mediated noradrenaline release were measured to predict its potential cognitive enhancing properties. Finally, an object recognition test performed in mice revealed that 24 was able to significantly enhance cognition, after oral administration, at doses as low as 0.3 mg/kg. This study validates the interest of the isosteric replacement of the benzene or pyridine nuclei by the thiophene nucleus in the ring-fused thiadiazine dioxides class of AMPA potentiators.

  DOI：

  10.1021/jm400676g
• 作为产物：
  描述：

  3-叠氮基-N-(叔丁基)-5-氯噻吩-2-磺酰胺 在 十六烷基三丁基溴化磷 、 sodium tetrahydroborate 、 盐酸 作用下， 生成 3-amino-5-chlorothiophene-2-sulfonamide
  参考文献：
  名称：

  Development of Thiophenic Analogues of Benzothiadiazine Dioxides as New Powerful Potentiators of 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid (AMPA) Receptors

  摘要：

  On the basis of the results obtained in previous series of AMPA potentiators belonging to 3,4-dihydro-2H-benzo- and 3,4-dihydro-2H-pyrido-1,2,4-thiadiazine 1,1-dioxides, the present work focuses on the design of original isosteric 3,4-dihydro-2H-thieno-1,2,4-thiadiazine 1,1-dioxides. Owing to the sulfur position, three series of compounds were developed and their activity as AMPA potentiators was characterized. In each of the developed series, potent compounds were discovered. After screening the selected active compounds on a safety in vivo test, 6-chloro-4-ethyl-3,4-dihydro-2H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide (24) appeared as the most promising compound and was further evaluated. Its effects on long-term potentiation in vivo and on AMPA-mediated noradrenaline release were measured to predict its potential cognitive enhancing properties. Finally, an object recognition test performed in mice revealed that 24 was able to significantly enhance cognition, after oral administration, at doses as low as 0.3 mg/kg. This study validates the interest of the isosteric replacement of the benzene or pyridine nuclei by the thiophene nucleus in the ring-fused thiadiazine dioxides class of AMPA potentiators.

  DOI：

  10.1021/jm400676g

文献信息

• Anti-infective agents
  申请人：——

  公开号：US20040162285A1

  公开（公告）日：2004-08-19

  Compounds having the formula 1 are hepatitis C(HCV) polymerase inhibitors. Also disclosed are a composition and method for inhibiting hepatitis C(HCV) polymerase, processes for making the compounds, and synthetic intermediates employed in the processes.

  具有公式1的化合物是丙型肝炎病毒（HCV）聚合酶抑制剂。还公开了一种用于抑制丙型肝炎病毒（HCV）聚合酶的组成和方法，用于制造这些化合物的过程，以及在这些过程中使用的合成中间体。
• Synthesis of carbon-14 and stable isotope labelled NN414: a potent potassium channel opener
  作者：Steen K. Johansen、Jesper B. Kristensen、Lars K. Müller、Claus U. Jessen、Christian Foged

  DOI：10.1002/jlcr.805

  日期：2004.2

  Currently, NN414, a potent β-cell selective potassium channel opener, is undergoing clinical trials for the treatment of type 2 diabetes. Here, we report the synthesis of carbon-14 and stable isotope labelled NN414 for use in metabolic studies and as an internal standard in pharmacokinetic assays, respectively. The carbon-14 labelling was performed in two steps starting from an advanced intermediate. This provided [14C]NN414 in 60% overall radiochemical yield with a specific activity of 58mCi/mmol. The stable isotope labelling was accomplished from benzyl tert-butyl malonate in eight steps using [13C,2H3]iodomethane and [2H2]dibromomethane as the source of carbon-13/deuterium. The synthetic sequence, which included a Mannich reaction followed by deamination, a Simmons–Smith-type cyclopropanation and a modified Curtius reaction, provided [13C,2H5]NN414 in 8.6% overall yield. Copyright © 2004 John Wiley & Sons, Ltd.

  目前，NN414是一种有效的β细胞选择性钾通道开放剂，正在进行治疗2型糖尿病的临床试验。在这里，我们报告了碳 14 和稳定同位素标记的 NN414 的合成，分别用于代谢研究和药代动力学测定中的内标。碳 14 标记从高级中间体开始分两步进行。这提供了总放射化学产率为 60% 且比活性为 58mCi/mmol 的 [14C]NN414。使用[13C,2H3]碘甲烷和[2H2]二溴甲烷作为碳13/氘源，通过八个步骤从丙二酸叔丁基苄酯完成稳定同位素标记。合成序列包括曼尼希反应、随后脱氨、西蒙斯-史密斯型环丙烷化和改进的库尔蒂斯反应，以 8.6% 的总产率提供 [13C,2H5]NN414。版权所有 © 2004 约翰·威利父子有限公司
• Nf-kappab inhibitors
  申请人：——

  公开号：US20040192943A1

  公开（公告）日：2004-09-30

  The present invention provides novel compounds and methods for using them to treat diseases with aminothiophene inhibitors of IKK-&bgr; phosphorylation of I&kgr;B. In so doing these aminothiophene inhibitors block pathological activation of transcription factor NF-&kgr;B in which diseases excessive activation of NF-&kgr;B is implicated.

  本发明提供了一种新型化合物及其使用方法，用于治疗使用IKK-&bgr;磷酸化I&kgr;B的氨基噻吩抑制剂治疗疾病。通过这样做，这些氨基噻吩抑制剂可以阻止转录因子NF-&kgr;B的异常激活，在这些疾病中，过度激活的NF-&kgr;B是其中的原因。
• Pyridazinone compounds
  申请人：Zhou Yuefen

  公开号：US20060189602A1

  公开（公告）日：2006-08-24

  The invention is directed to pyridazinone compounds and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.

  该发明涉及吡啶并咪唑酮化合物及含有该化合物的制药组合物，用于治疗丙型肝炎病毒感染。
• NF-κB inhibitors
  申请人：SmithKline Beecham Corporation

  公开号：US07166639B2

  公开（公告）日：2007-01-23

  The present invention provides novel compounds and methods for using them to treat diseases with aminothiophene inhibitors of IKK-β phosphorylation of IκB. In so doing these aminothiophene inhibitors block pathological activation of transcription factor NF-κB in which diseases excessive activation of NF-κB is implicated.

  本发明提供了新型化合物和使用它们治疗疾病的方法，其中使用IKK-β磷酸化IκB的氨基噻吩抑制剂来治疗疾病。通过这样做，这些氨基噻吩抑制剂阻止了转录因子NF-κB的病理活化，在其中疾病过度激活NF-κB被涉及。