2-(2-imino-5-methyl-1,3,4-thiadiazol-3(2H)-yl)-1-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)ethanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 2-(2-imino-5-methyl-1,3,4-thiadiazol-3(2H)-yl)-1-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)ethanone
• 英文别名: 2-(2-Imino-5-methyl-1,3,4-thiadiazol-3-yl)-1-[2-(trifluoromethyl)phenothiazin-10-yl]ethanone；2-(2-imino-5-methyl-1,3,4-thiadiazol-3-yl)-1-[2-(trifluoromethyl)phenothiazin-10-yl]ethanone
• 化学式: C₁₈H₁₃F₃N₄OS₂
• 分子量: 422.455
• InChiKey: POIWOJMJUNYPKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-三氟甲基吩噻嗪 以 乙醇 、 甲苯 为溶剂， 反应 29.0h， 生成 2-(2-imino-5-methyl-1,3,4-thiadiazol-3(2H)-yl)-1-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)ethanone
  参考文献：
  名称：

  Design of new phenothiazine-thiadiazole hybrids via molecular hybridization approach for the development of potent antitubercular agents

  摘要：

  A new library of phenothiazine and 1,3,4-thiadiazole hybrid derivatives (5a-u) was designed based on the molecular hybridization approach and the molecules were synthesized in excellent yields using a facile single-step chloro-amine coupling reaction between 2-chloro-1-(10H-phenothiazin-10-yl)ethanones and 2-amino-5-subsituted-1,3,4-thiadiazoles. The compounds were evaluated for their in vitro inhibition activity against Mycobacterium tuberculosis H37Rv (MTB). Compounds 5g and 5n were emerged as the most active compounds of the series with MIC of 0.8 mu g/mL (similar to 1.9 mu M). Also, compounds 5a, 5b, 5c, 5e, 5l and 5m (MIC = 1.6 mu g/mL), and compounds 5j, 5k and 5o (MIC = 3.125 mu g/mL) showed significant inhibition activity. The structure-activity relationship demonstrated that an alkyl (methyl/n-propyl) or substituted (4-methyl/4-Cl/4-F) phenyl groups on the 1,3,4-thiadiazole ring enhance the inhibition activity of the compounds. The cytotoxicity study revealed that none of the active molecules are toxic to a normal Vero cell line thus proving the lack of general cellular toxicity. Further, the active molecules were subjected to molecular docking studies with target enzymes InhA and CYP121. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.035

文献信息

• Design of new phenothiazine-thiadiazole hybrids via molecular hybridization approach for the development of potent antitubercular agents
  作者：Jurupula Ramprasad、Nagabhushana Nayak、Udayakumar Dalimba

  DOI：10.1016/j.ejmech.2015.10.035

  日期：2015.12

  A new library of phenothiazine and 1,3,4-thiadiazole hybrid derivatives (5a-u) was designed based on the molecular hybridization approach and the molecules were synthesized in excellent yields using a facile single-step chloro-amine coupling reaction between 2-chloro-1-(10H-phenothiazin-10-yl)ethanones and 2-amino-5-subsituted-1,3,4-thiadiazoles. The compounds were evaluated for their in vitro inhibition activity against Mycobacterium tuberculosis H37Rv (MTB). Compounds 5g and 5n were emerged as the most active compounds of the series with MIC of 0.8 mu g/mL (similar to 1.9 mu M). Also, compounds 5a, 5b, 5c, 5e, 5l and 5m (MIC = 1.6 mu g/mL), and compounds 5j, 5k and 5o (MIC = 3.125 mu g/mL) showed significant inhibition activity. The structure-activity relationship demonstrated that an alkyl (methyl/n-propyl) or substituted (4-methyl/4-Cl/4-F) phenyl groups on the 1,3,4-thiadiazole ring enhance the inhibition activity of the compounds. The cytotoxicity study revealed that none of the active molecules are toxic to a normal Vero cell line thus proving the lack of general cellular toxicity. Further, the active molecules were subjected to molecular docking studies with target enzymes InhA and CYP121. (C) 2015 Elsevier Masson SAS. All rights reserved.