2-(3-(trifluoromethyl)benzoyl)hydrazinecarbothioamide | 7653-35-2

• 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-(3-(trifluoromethyl)benzoyl)hydrazinecarbothioamide
• 英文别名: 1-(3-trifluoromethyl-benzoyl)-thiosemicarbazide；1--3-thiosemicarbazid；1-(3-Trifluormethyl-benzoyl)-thiosemicarbazid；[[3-(trifluoromethyl)benzoyl]amino]thiourea
• CAS: 7653-35-2
• 化学式: C₉H₈F₃N₃OS
• mdl: MFCD00276815
• 分子量: 263.243
• InChiKey: VQAOAFRWYYKQRP-UHFFFAOYSA-N

物化性质

• 熔点：
  210-212 °C
• 密度：
  1.456±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  99.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(3-(trifluoromethyl)benzoyl)hydrazinecarbothioamide 在 Oxone 、 碘 、 sodium hydroxide 作用下， 以 水 、 异丙醇 为溶剂， 反应 0.5h， 以59%的产率得到5-[3-(三氟甲基)苯基]-1,3,4-恶二唑-2-胺
  参考文献：
  名称：

  A Convenient Synthesis of 5-substituted 2-amino-1,3,4-oxadiazoles from Corresponding Acylthiosemicarbazides Using iodine and Oxone®

  摘要：

  我们开发了一种简便的方法，在 Oxone® 作为大量氧化剂存在的情况下，使用催化量的碘/KI，从相应的酰基硫代氨基甲酰肼合成取代的 2-氨基-1,3,4-恶二唑。这种方法具有反应时间短、底物可变性强的优点，适合快速生产先导优化计划所需的类似物。由于反应条件温和，且使用的试剂在商业上既便宜又安全，因此该方法也可用于大规模合成。

  DOI：

  10.3184/174751912x13551638283701
• 作为产物：
  描述：

  3-三氟甲基苯甲酸 在 吡啶 、 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 生成 2-(3-(trifluoromethyl)benzoyl)hydrazinecarbothioamide
  参考文献：
  名称：

  Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents

  摘要：

  Resistance among dormant mycobacteria leading to multidrug‐resistant and extremely drug‐resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4‐triazole‐3‐thione and 1,3,4‐oxadiazole‐2‐thione derivatives (4a–5c) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC50) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram‐negative and Gram‐positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100 μg/ml against THP‐1, A549, and PANC‐1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.

  DOI：

  10.1111/cbdd.12939

文献信息

• Semisynthetic pleuromutilin antimicrobials with therapeutic potential against methicillin-resistant Staphylococcus aureus by targeting 50S ribosomal subunit
  作者：Xiao Wang、Rui Wang、Zhao-Sheng Zhang、Guang-Yu Zhang、Zhen Jin、Rong Shen、Dan Du、You-Zhi Tang

  DOI：10.1016/j.ejmech.2022.114341

  日期：2022.7

  successfully localized inside the binding pocket of 50S ribosomal subunit (ΔGb = −9.40 kcal/mol). Meanwhile, most of these compounds had no significant inhibitory effect on RAW 264.7 cells and 16HBE cells at the concentration of 8 μg/mL. The obtained outcomes showed that compound 30a could be utilized as an encouraging perspective in the development of a new therapeutic candidate for bacterial infection.

  设计、合成了一系列具有取代的1,2,4-三唑的截短侧耳素类似物，并评估了它们的体外和体内抗菌活性。最初，通过肉汤稀释法测试了合成的衍生物对五株金黄色葡萄球菌（MRSA ATCC 43300、金黄色葡萄球菌ATCC 29213、临床分离的金黄色葡萄球菌AD3、金黄色葡萄球菌144 和金黄色葡萄球菌SA17）的 MIC。 。化合物30a 、 31b和32a是体外针对MRSA最有效的抗菌剂(MIC=0.0625μg/mL)。时间杀灭曲线结果表明，化合物30a和32a可以在体外快速减少MRSA的量（减少-7.70 log 10 CFU/mL和-7.10 log 10 CFU/mL）。在进一步评估化合物30a针对MRSA的体内抗菌活性的实验中，化合物30a （-1.71 log10 CFU/g）可有效减少大腿感染小鼠的MRSA载量。在小鼠全身模型中，化合物30a （存活率为50%）显示出优于泰妙菌素
• Discovery and Biophysical Characterization of 2-Amino-oxadiazoles as Novel Antagonists of PqsR, an Important Regulator of Pseudomonas aeruginosa Virulence
  作者：Michael Zender、Tobias Klein、Claudia Henn、Benjamin Kirsch、Christine K. Maurer、Dagmar Kail、Christiane Ritter、Olan Dolezal、Anke Steinbach、Rolf W. Hartmann

  DOI：10.1021/jm400830r

  日期：2013.9.12

  The human pathogen Pseudomonas aeruginosa employs alkyl quinolones for cell-to-cell communication. The Pseudomonas quinolone signal (PQS) regulates various virulence factors via interaction with the transcriptional regulator PqsR. Therefore, we consider the development of PqsR antagonists a novel strategy to limit the pathogenicity of P. aeruginosa. A fragment identification approach using surface plasmon resonance screening led to the discovery of chemically diverse PqsR ligands. The optimization of the most promising hit (5) resulted in the oxadiazole-2-amine 37 showing pure antagonistic activity in Escherichia coli (EC50 = 7.5 mu M) and P. aeruginosa (EC50 = 38.5 mu M) reporter gene assays. 37 was able to diminish the production of the PQS precursor HHQ in a PqsH-deficient P. aeruginosa mutant The level of the major virulence factor pyocyanin was significantly reduced in wild-type P. aeruginosa. In addition, site-directed mutagenesis in combination with isothermal titration calorimetry and NMR INPHARMA experiments revealed that the identified ligands bind to the same site of PqsR by adopting different binding modes. These findings will be utilized in a future fragment growing approach aiming at novel therapeutic options for the treatment of P. aeruginosa infections.
• 2-Amino-5-Substituted 1,3,4-Oxadiazoles and 5-Imino-2-Substituted Δ²-1,3,4-Oxadiazolines. A Group of Novel Muscle Relaxants
  作者：Harry L. Yale、Kathryn Losee

  DOI：10.1021/jm00322a007

  日期：1966.7
• Lalezari,I.; Sharghi,N., Journal of Heterocyclic Chemistry, 1966, vol. 3, p. 336 - 337
  作者：Lalezari,I.、Sharghi,N.

  DOI：——

  日期：——
• Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents
  作者：Amol D. Sonawane、Navnath D. Rode、Laxman Nawale、Rohini R. Joshi、Ramesh A. Joshi、Anjali P. Likhite、Dhiman Sarkar

  DOI：10.1111/cbdd.12939

  日期：2017.8

  Resistance among dormant mycobacteria leading to multidrug‐resistant and extremely drug‐resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4‐triazole‐3‐thione and 1,3,4‐oxadiazole‐2‐thione derivatives (4a–5c) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC50) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram‐negative and Gram‐positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100 μg/ml against THP‐1, A549, and PANC‐1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.