2-(1-(4-methyl-2-(4-(piperidin-1-yl)phenyl)thiazol-5-yl)ethylidene)hydrazine-1-carboximidamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-(1-(4-methyl-2-(4-(piperidin-1-yl)phenyl)thiazol-5-yl)ethylidene)hydrazine-1-carboximidamide
• 化学式: C₁₈H₂₄N₆S
• 分子量: 356.495
• InChiKey: XJJSOTZPTFNTDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.32
• 重原子数：
  25.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  90.39
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  4-氯硫代苯甲酰胺 在 盐酸 、 potassium tert-butylate 、 palladium diacetate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 9.0h， 生成 2-(1-(4-methyl-2-(4-(piperidin-1-yl)phenyl)thiazol-5-yl)ethylidene)hydrazine-1-carboximidamide
  参考文献：
  名称：

  Phenylthiazoles with nitrogenous side chain: An approach to overcome molecular obesity

  摘要：

  A novel series of phenylthiazoles bearing cyclic amines at the phenyl-4 position was prepared with the objective of decreasing lipophilicity and improving the overall physicochemical properties and pharmacokinetic profile of the compounds. Briefly, the piperidine ring (compounds 10 and 12) provided the best ring size in terms of antibacterial activity when tested against 16 multidrug-resistant clinical isolates. Both compounds were superior to vancomycin in the ability to eliminate methicillin-resistant Staphylococcus aureus (MRSA), residing within infected macrophages and to disrupt mature MRSA biofilm. Additionally, compounds 10 and 12 exhibited a fast-bactericidal mode of action in vitro. Furthermore, the new derivatives were 160-times more soluble in water than the previous lead compound 1b. Consequently, compound 10 was orally bioavailable with a highly-acceptable pharmacokinetic profile in vivo that exhibited a half-life of 4 h and achieved a maximum plasma concentration that exceeded the minimum inhibitory concentration (MIC) values against all tested bacterial isolates. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111593

文献信息

• Phenylthiazoles with nitrogenous side chain: An approach to overcome molecular obesity
  作者：Mohamed M. Elsebaei、Nader S. Abutaleb、Abdulrahman A. Mahgoub、Daoyi Li、Mohamed Hagras、Haroon Mohammad、Mohamed N. Seleem、Abdelrahman S. Mayhoub

  DOI：10.1016/j.ejmech.2019.111593

  日期：2019.11

  A novel series of phenylthiazoles bearing cyclic amines at the phenyl-4 position was prepared with the objective of decreasing lipophilicity and improving the overall physicochemical properties and pharmacokinetic profile of the compounds. Briefly, the piperidine ring (compounds 10 and 12) provided the best ring size in terms of antibacterial activity when tested against 16 multidrug-resistant clinical isolates. Both compounds were superior to vancomycin in the ability to eliminate methicillin-resistant Staphylococcus aureus (MRSA), residing within infected macrophages and to disrupt mature MRSA biofilm. Additionally, compounds 10 and 12 exhibited a fast-bactericidal mode of action in vitro. Furthermore, the new derivatives were 160-times more soluble in water than the previous lead compound 1b. Consequently, compound 10 was orally bioavailable with a highly-acceptable pharmacokinetic profile in vivo that exhibited a half-life of 4 h and achieved a maximum plasma concentration that exceeded the minimum inhibitory concentration (MIC) values against all tested bacterial isolates. (C) 2019 Elsevier Masson SAS. All rights reserved.