(E)-2-cyano-N-(4-{[(3,4-dimethylisoxazol-5-yl)amino]sulfonyl}phenyl)-3-mercapto-3-(methylamino)acrylamide

• 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: (E)-2-cyano-N-(4-{[(3,4-dimethylisoxazol-5-yl)amino]sulfonyl}phenyl)-3-mercapto-3-(methylamino)acrylamide
• 英文别名: (E)-2-cyano-N-[4-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-3-(methylamino)-3-sulfanylprop-2-enamide
• 化学式: C₁₆H₁₇N₅O₄S₂
• 分子量: 407.474
• InChiKey: VJANCNFEFSEBLD-DTQAZKPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.92
• 重原子数：
  27.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  137.12
• 氢给体数：
  4.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (E)-2-cyano-N-(4-{[(3,4-dimethylisoxazol-5-yl)amino]sulfonyl}phenyl)-3-mercapto-3-(methylamino)acrylamide 、 acetobromogalactose 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 18.0h， 以61%的产率得到(E)-2-cyano-N-(4-{[(3,4-dimethylisoxazol-5-yl)amino]sulfonyl}phenyl)-3-(methylamino)-3-(2′,3′,4′,6′-tetra-O-acetyl-β-D-galactopyranosylthio)acrylamide
  参考文献：
  名称：

  New acrylamide-sulfisoxazole conjugates as dihydropteroate synthase inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2020.115444
• 作为产物：
  描述：

  磺胺异噁唑 在 盐酸 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 (E)-2-cyano-N-(4-{[(3,4-dimethylisoxazol-5-yl)amino]sulfonyl}phenyl)-3-mercapto-3-(methylamino)acrylamide
  参考文献：
  名称：

  New acrylamide-sulfisoxazole conjugates as dihydropteroate synthase inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2020.115444

文献信息

• 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.