1-[S-(4-nitrophenyl)sulfonimidoyl]piperidine | 18513-11-6

• 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: 1-[S-(4-nitrophenyl)sulfonimidoyl]piperidine
• 英文别名: 1-(4-nitrophenylsulfonimidoyl)piperidine
• CAS: 18513-11-6
• 化学式: C₁₁H₁₅N₃O₃S
• 分子量: 269.324
• InChiKey: KSVOGTBYLKVTHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  87.3
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1-[S-(4-nitrophenyl)sulfonimidoyl]piperidine 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  N-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines: Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity

  摘要：

  Herein we demonstrate the expanded utility of a recently described N-trifluoromethylthiolation protocol to sulfonimidamide containing substances. The novel N-trifluoromethylthio sulfonimidamide derivatives thus obtained were evaluated for antibacterial activity against Mycobacterium tuberculosis (M. tb.) and Mycobacterium abscessus and Gram + Ve (Streptococcus aureus, Bacillus subtilis), and Gram - Ve (Escherichia coli, Pseudomonas aeruginosa) bacteria. Two compounds, 13 and 15 showed high antimycobacterial activity with MIC value of 4-8 mu g/mL; i.e. comparable to WHO recommended first line antibiotic for TB infection ethambutol. The same compounds were also found to be cytotoxic in HepG2 cells (compound 13 IC50 = 15 mu g/mL; compound 15 IC50 = 65 mu g/mL). A structure activity relationship, using matched pair analysis, gave the unexpected conclusion that the trifluoromethylthio moiety was responsible for the cellular and bacterial toxicity. Given the increasing use of the trifluoromethylthio group in contemporary medicinal chemistry, this observation calls for considerations before implementation of the functionality in drug design.

  DOI：

  10.1021/acsmedchemlett.9b00285
• 作为产物：
  描述：

  4-硝基苯磺酰胺 在 甲酸 、 三乙胺 、 三苯基二氯化膦 作用下， 以 氯仿 、 水 、 甲苯 、 乙腈 为溶剂， 反应 48.0h， 生成 1-[S-(4-nitrophenyl)sulfonimidoyl]piperidine
  参考文献：
  名称：

  N-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines: Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity

  摘要：

  Herein we demonstrate the expanded utility of a recently described N-trifluoromethylthiolation protocol to sulfonimidamide containing substances. The novel N-trifluoromethylthio sulfonimidamide derivatives thus obtained were evaluated for antibacterial activity against Mycobacterium tuberculosis (M. tb.) and Mycobacterium abscessus and Gram + Ve (Streptococcus aureus, Bacillus subtilis), and Gram - Ve (Escherichia coli, Pseudomonas aeruginosa) bacteria. Two compounds, 13 and 15 showed high antimycobacterial activity with MIC value of 4-8 mu g/mL; i.e. comparable to WHO recommended first line antibiotic for TB infection ethambutol. The same compounds were also found to be cytotoxic in HepG2 cells (compound 13 IC50 = 15 mu g/mL; compound 15 IC50 = 65 mu g/mL). A structure activity relationship, using matched pair analysis, gave the unexpected conclusion that the trifluoromethylthio moiety was responsible for the cellular and bacterial toxicity. Given the increasing use of the trifluoromethylthio group in contemporary medicinal chemistry, this observation calls for considerations before implementation of the functionality in drug design.

  DOI：

  10.1021/acsmedchemlett.9b00285

文献信息

• 3D Heterocycles from Sulfonimidamides by Sequential C−H Bond Alkenylation/Aza‐Michael Cyclization
  作者：Anne‐Katrin Bachon、Alina Hermann、Carsten Bolm

  DOI：10.1002/chem.201900920

  日期：2019.4.23

  rhodium‐catalyzed C−H bond alkenylation followed by aza‐Michael cyclization leads to unprecedented benzoisothiazole 1‐oxides. The applicability and robustness of the method is demonstrated in 25 examples with yields up to 95 %. The resulting scaffolds are partly saturated, 3D heterocycles with potential significance for medicinal and agricultural chemistry.

  从开始NH -sulfonimidamides，铑催化的C-H键烯基化，接着氮杂-迈克尔环化导致了前所未有的苯并异噻唑-1-氧化物。在25个实例中证明了该方法的适用性和鲁棒性，产率高达95％。所得支架为部分饱和的3D杂环，对药物和农业化学具有潜在意义。
• Copper-Catalyzed S−C/S−N Bond Interconversions
  作者：Jian Wen、Hanchao Cheng、Shunxi Dong、Carsten Bolm

  DOI：10.1002/chem.201600661

  日期：2016.4.11

  de‐alkylation/amination sequences provide sulfonimidamides from unprotected sulfoximines in moderate to good yields. Mechanistic studies suggest the involvement of radicals in both the C−S bond cleavage and the formation of the new N−S bond.

  在双氧气氛下，铜催化的脱烷基化/胺化顺序可从未保护的亚砜亚胺以中等到良好的收率提供亚磺酰胺。机理研究表明，自由基参与CS键的断裂和新的NS键的形成。
• A New, Practical One-Pot Synthesis of Unprotected Sulfonimidamides by Transfer of Electrophilic NH to Sulfinamides
  作者：Flavia Izzo、Martina Schäfer、Robert Stockman、Ulrich Lücking

  DOI：10.1002/chem.201703272

  日期：2017.10.26

  An NH transaction: The first direct synthesis of tertiary NH sulfonimidamides from tertiary sulfinamides by electrophilic NH transfer has been achieved. In vitro studies did not reveal any intrinsic flaw of the sulfonimidamide group regarding properties relevant to medicinal chemistry.

  NH交易：已经实现了通过亲电NH转移从叔亚磺酰胺直接合成叔NH磺酰亚胺酰胺的方法。体外研究并未发现磺胺类药物组在与药物化学有关的性质方面有任何内在缺陷。
• 1,2‐Benzothiazine Derivatives from Sulfonimidamides by Metal‐Catalyzed Annulation Reactions in Solution and under Solvent‐Free Mechanochemical Conditions
  作者：Jan‐Hendrik Schöbel、Philipp Elbers、Khai‐Nghi Truong、Kari Rissanen、Carsten Bolm

  DOI：10.1002/adsc.202001505

  日期：2021.3.2

  different protocols are presented. The first is a rhodium‐catalyzed annulation reaction with α‐sulfonyloxyketones leading to 4‐unsubstituted benzothiazine derivatives. By selective bromination with NBS the heterocyclic ring can further be functionalized. In the second approach, an iridium catalyst is applied under solvent‐free mechanochemical conditions providing products with 3,4‐disubstituted thiazine rings

  1,2-苯并噻嗪1,1-二氧化物的三维氮杂类似物是由亚磺酰胺制备的。提出了两种不同的协议。第一个是铑催化的与α-磺酰氧基酮的环化反应，生成4-未取代的苯并噻嗪衍生物。通过用NBS选择性溴化，杂环可以进一步被官能化。在第二种方法中，在无溶剂的机械化学条件下使用铱催化剂，以从重氮酮酸酯和重氮酮砜中产生具有3,4-二取代的噻嗪环的产物。