2-氰基-N-(4-{[(3,4-二甲基异恶唑-5-基)氨基]磺酰基}苯基)乙酰胺 | 546090-57-7

• 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: 2-氰基-N-(4-{[(3,4-二甲基异恶唑-5-基)氨基]磺酰基}苯基)乙酰胺
• 英文名称: 2-cyano-N-(4-{[(3,4-dimethylisoxazole-5-yl)amino]sulfonyl}phenyl)acetamide
• 英文别名: 2-cyano-N-(4-{[(3,4-dimethylisoxazol-5-yl)amino]sulfonyl}phenyl)acetamide；2-cyano-N-[4-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]acetamide
• CAS: 546090-57-7
• 化学式: C₁₄H₁₄N₄O₄S
• mdl: MFCD03394770
• 分子量: 334.356
• InChiKey: OJRYIUWXXBRFTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  7

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2935009090

反应信息

• 作为反应物：
  描述：

  2-氰基-N-(4-{[(3,4-二甲基异恶唑-5-基)氨基]磺酰基}苯基)乙酰胺 在 哌啶 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 15.0h， 生成 4-[3,5-dicyano-4-(2-furyl)-6-mercapto-2-oxopyridin-1(2H)-yl]-N-(3,4-dimethylisoxazol-5-yl)benzenesulfonamide
  参考文献：
  名称：

  Design, synthesis, antimicrobial evaluation and molecular docking studies of some new thiophene, pyrazole and pyridone derivatives bearing sulfisoxazole moiety

  摘要：

  Development of new antimicrobial agents is a good solution to overcome drug-resistance problems. In this context, new functionalized thiophene, acrylamide, arylhydrazone, pyrazole and pyridone derivatives bearing sulfisoxazole moiety were designed, synthesized and evaluated for their in vitro antibacterial and antifungal activities. Among the synthesized compounds, thiophene 4d and 6-thioglucosylpyridone 17 displayed significant antibacterial activities against Escherichia coli (MIC, 0.007 μg/mL vs gentamycin 1.95 μg/mL) and Bacillis subtilis (MIC, 0.007 μg/mL vs ampicillin 0.24 μg/mL), respectively. Whereas, the pyrazole 6 showed the highest antifungal activity against Aspergillus fumigates (MIC, 0.03 μg/mL vs amphotericin B 0.12 μg/mL). In general, most of the synthesized compounds exhibited better antimicrobial activities than sulfisoxazole; this might be attributed to the synergistic effect of the sulfonamide and attached heterocyclic moieties as well as the increased lipophilic characters of the synthesized compounds. Molecular docking studies indicated that the synthesized compounds could occupy both p-amino benzoic acid (PABA) and pterin binding pockets of the dihydropteroate synthase (DHPS), suggesting that the target compounds could act by the inhibition of microbial DHPS enzyme. The results provide important information for the future design of more potent antimicrobial agents.

  DOI：

  10.1016/j.ejmech.2014.07.052
• 作为产物：
  描述：

  磺胺异噁唑 、 1-cyanoacetyl-3,5-dimethylpyrazole 以 1,4-二氧六环 为溶剂， 生成 2-氰基-N-(4-{[(3,4-二甲基异恶唑-5-基)氨基]磺酰基}苯基)乙酰胺
  参考文献：
  名称：

  Design, synthesis, antimicrobial evaluation and molecular docking studies of some new 2,3-dihydrothiazoles and 4-thiazolidinones containing sulfisoxazole

  摘要：

  Microbial resistance to the available drugs poses a serious threat in modern medicine. We report the design, synthesis and in vitro antimicrobial evaluation of new functionalized 2,3-dihydrothiazoles and 4-thiazolidinones tagged with sulfisoxazole moiety. Compound 8d was most active against Bacillis subtilis (MIC, 0.007 mu g/mL). Moreover, compounds 7c-d and 8c displayed significant activities against B. subtilis and Streptococcus pneumoniae (MIC, 0.03-0.06 mu g/mL and 0.06-0.12 mu g/mL versus ampicillin 0.24 mu g/mL and 0.12 mu g/mL; respectively). Compounds 7a and 7c-d were highly potent against Escherichia coli (MIC, 0.49-0.98 mu g/mL versus gentamycin 1.95 mu g/mL). On the other hand, compounds 7e and 9c were fourfolds more active than amphotericin B against Syncephalastrum racemosum. Molecular docking studies showed that the synthesized compounds could act as inhibitors for the dihydropteroate synthase enzyme (DHPS). This study is a platform for the future design of more potent antimicrobial agents.

  DOI：

  10.3109/14756366.2015.1016514

文献信息

• Novel hydrazide-hydrazone and amide substituted coumarin derivatives: Synthesis, cytotoxicity screening, microarray, radiolabeling and in vivo pharmacokinetic studies
  作者：Tamer Nasr、Samir Bondock、Hassan M. Rashed、Walid Fayad、Mahmoud Youns、Tamer M. Sakr

  DOI：10.1016/j.ejmech.2018.04.014

  日期：2018.5

  presents BCHHD 11b as a potent anticancer agent able to overcome drug resistance. In addition, compound 11b was able to serve as a chemical carrier for 99mTc and the in vivo biodistribution study of 99mTc-11b complex revealed a remarkable targeting ability of 99mTc into solid tumor showing that 99mTc-11b might be used as a promising radiopharmaceutical imaging agent for cancer.

  当前的工作提出了新的香豆素酰肼-系列衍生物的合成和生物学评估，这些衍生物显示了使用阿霉素对耐药胰腺癌（Panc-1），肝细胞癌（HepG2）和白血病（CCRF）细胞系的体外广谱抗肿瘤活性作为参考标准。溴香豆素酰肼-衍生物（BCHHD）11b对所有测试的癌细胞系均显示出优异的抗癌活性。酶分析表明，由于胱天蛋白酶3/7的激活，BCHHD 11b诱导了细胞凋亡。此外，11b以剂量依赖性方式抑制GST和CYP3A4，诱导的细胞死亡可归因于代谢抑制。此外，11b基因芯片分析显示，处理过的细胞中许多与凋亡，细胞周期，肿瘤生长和抑制基因。以上所有内容均提出了BCHHD 11b，它是一种能够克服耐药性的有效抗癌剂。此外，化合物11b可以作为99mTc的化学载体，对99mTc-11b复合物的体内生物分布研究表明99mTc对实体瘤具有显着的靶向能力，表明99mTc-11b可以用作有前途的放射性药物显像剂对于癌症。
• New acrylamide-sulfisoxazole conjugates as dihydropteroate synthase inhibitors
  作者：Tamer Nasr、Samir Bondock、Tamer M. Ibrahim、Walid Fayad、Ahmed B. Ibrahim、Neveen A. AbdelAziz、Tamer M. Sakr

  DOI：10.1016/j.bmc.2020.115444

  日期：2020.5

  New functionalized acrylamide derivatives bearing sulfisoxazole moiety were designed to target bacterial di-hydropteroate synthase (DHPS). The in vitro antimicrobial activities of these compounds were assessed. The E-configuration of compound 5b was proved by single crystal X-ray analysis. Compounds 5g and 5h displayed double the activity of ampicillin against B. subtilis. Also, 5h was two times more active than gentamycin against E. coli. Interestingly, compounds 5f-g, 7c, 8a, 8c exhibited two folds the potency of amphotericin B against S. racemosum while 5h displayed three folds the activity of amphotericin B against S. racemosum. Most of the synthesized compounds showed superior activities to the parent sulfisoxazole and were non-toxic to normal cells. DHPS is confirmed to be a putative target for our compounds via antagonizing their antibacterial activity by the folate precursor (p-aminobenzoic acid) and product (methionine) on E. coli ATCC 25922. Docking experiments against DHPS rationalized the observed antibacterial activity. Additionally, compound 5g was evaluated as a selective targeting vector for Tc-99m that showed a remarkable uptake and targeting ability towards the infection site that was induced in mice.
• Design, synthesis, antimicrobial evaluation and molecular docking studies of some new thiophene, pyrazole and pyridone derivatives bearing sulfisoxazole moiety
  作者：Tamer Nasr、Samir Bondock、Sameh Eid

  DOI：10.1016/j.ejmech.2014.07.052

  日期：2014.9

  Development of new antimicrobial agents is a good solution to overcome drug-resistance problems. In this context, new functionalized thiophene, acrylamide, arylhydrazone, pyrazole and pyridone derivatives bearing sulfisoxazole moiety were designed, synthesized and evaluated for their in vitro antibacterial and antifungal activities. Among the synthesized compounds, thiophene 4d and 6-thioglucosylpyridone 17 displayed significant antibacterial activities against Escherichia coli (MIC, 0.007 μg/mL vs gentamycin 1.95 μg/mL) and Bacillis subtilis (MIC, 0.007 μg/mL vs ampicillin 0.24 μg/mL), respectively. Whereas, the pyrazole 6 showed the highest antifungal activity against Aspergillus fumigates (MIC, 0.03 μg/mL vs amphotericin B 0.12 μg/mL). In general, most of the synthesized compounds exhibited better antimicrobial activities than sulfisoxazole; this might be attributed to the synergistic effect of the sulfonamide and attached heterocyclic moieties as well as the increased lipophilic characters of the synthesized compounds. Molecular docking studies indicated that the synthesized compounds could occupy both p-amino benzoic acid (PABA) and pterin binding pockets of the dihydropteroate synthase (DHPS), suggesting that the target compounds could act by the inhibition of microbial DHPS enzyme. The results provide important information for the future design of more potent antimicrobial agents.
• Design, synthesis, antimicrobial evaluation and molecular docking studies of some new 2,3-dihydrothiazoles and 4-thiazolidinones containing sulfisoxazole
  作者：Tamer Nasr、Samir Bondock、Sameh Eid

  DOI：10.3109/14756366.2015.1016514

  日期：2016.3.3

  Microbial resistance to the available drugs poses a serious threat in modern medicine. We report the design, synthesis and in vitro antimicrobial evaluation of new functionalized 2,3-dihydrothiazoles and 4-thiazolidinones tagged with sulfisoxazole moiety. Compound 8d was most active against Bacillis subtilis (MIC, 0.007 mu g/mL). Moreover, compounds 7c-d and 8c displayed significant activities against B. subtilis and Streptococcus pneumoniae (MIC, 0.03-0.06 mu g/mL and 0.06-0.12 mu g/mL versus ampicillin 0.24 mu g/mL and 0.12 mu g/mL; respectively). Compounds 7a and 7c-d were highly potent against Escherichia coli (MIC, 0.49-0.98 mu g/mL versus gentamycin 1.95 mu g/mL). On the other hand, compounds 7e and 9c were fourfolds more active than amphotericin B against Syncephalastrum racemosum. Molecular docking studies showed that the synthesized compounds could act as inhibitors for the dihydropteroate synthase enzyme (DHPS). This study is a platform for the future design of more potent antimicrobial agents.