N-(4-(2-(4-(tert-butyl)phenyl)-4-methylthiazol-5-yl)pyrimidin-2-yl)nicotinimidamide

• 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: N-(4-(2-(4-(tert-butyl)phenyl)-4-methylthiazol-5-yl)pyrimidin-2-yl)nicotinimidamide
• 英文别名: N'-[4-[2-(4-tert-butylphenyl)-4-methyl-1,3-thiazol-5-yl]pyrimidin-2-yl]pyridine-3-carboximidamide
• 化学式: C₂₄H₂₄N₆S
• 分子量: 428.561
• InChiKey: MFVOQTPIJKGOKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-{2-[4-(tert-butyl)phenyl]-4-methylthiazol-5-yl}ethanone 在 间氯过氧苯甲酸 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 N-(4-(2-(4-(tert-butyl)phenyl)-4-methylthiazol-5-yl)pyrimidin-2-yl)nicotinimidamide
  参考文献：
  名称：

  Phenylthiazoles with tert-Butyl side chain: Metabolically stable with anti-biofilm activity

  摘要：

  A new series of phenylthiazoles with t-butyl lipophilic component was synthesized and their antibacterial activity against a panel of multidrug-resistant bacterial pathogens was evaluated. Five compounds demonstrated promising antibacterial activity against methicillin-resistant staphylococcal strains and several vancomycin-resistant staphylococcal and enterococcal species. Additionally, three derivatives 19, 23 and 26 exhibited rapid bactericidal activity, and remarkable ability to disrupt mature biofilm produced by MRSA USA300. More importantly, a resistant mutant to 19 couldn't be isolated after subjecting MRSA to sub-lethal doses for 14 days. Lastly, this new series of phenylthiazoles possesses an advantageous attribute over the first-generation compounds in their stability to hepatic metabolism, with a biological half-life of more than 9 h. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.044

文献信息

• PHENYLTHIAZOLES AND USES THEREOF
  申请人：Purdue Research Foundation

  公开号：US20180319784A1

  公开（公告）日：2018-11-08

  Series of 2-phenyl-4-methylthiazole analogues are disclosed as potential therapeutic agents for the treatment of bacterial infections, especially methicillin-resistant Straphylococcus aureus (MRSA) related infections. A method for the treatment of MRSA-related infections is also claimed.

  一系列2-苯基-4-甲基噻唑类似物被披露为治疗细菌感染，特别是耐甲氧西林金黄色葡萄球菌（MRSA）相关感染的潜在治疗药物。还声明了一种治疗MRSA相关感染的方法。
• Phenylthiazoles and uses thereof
  申请人：Purdue Research Foundation

  公开号：US10414759B2

  公开（公告）日：2019-09-17

  Series of 2-phenyl-4-methylthiazole analogs are disclosed as potential therapeutic agents for the treatment of bacterial infections, especially methicillin-resistant Straphylococcus aureus (MRSA) related infections. A method for the treatment of MRSA-related infections is also claimed.

  本发明公开了一系列 2-苯基-4-甲基噻唑类似物，它们是治疗细菌感染，特别是耐甲氧西林金黄色葡萄球菌（MRSA）相关感染的潜在治疗剂。还提出了一种治疗 MRSA 相关感染的方法。
• Phenylthiazoles with tert-Butyl side chain: Metabolically stable with anti-biofilm activity
  作者：Ahmed Kotb、Nader S. Abutaleb、Mohamed A. Seleem、Mohamed Hagras、Haroon Mohammad、Ashraf Bayoumi、Adel Ghiaty、Mohamed N. Seleem、Abdelrahman S. Mayhoub

  DOI：10.1016/j.ejmech.2018.03.044

  日期：2018.5

  A new series of phenylthiazoles with t-butyl lipophilic component was synthesized and their antibacterial activity against a panel of multidrug-resistant bacterial pathogens was evaluated. Five compounds demonstrated promising antibacterial activity against methicillin-resistant staphylococcal strains and several vancomycin-resistant staphylococcal and enterococcal species. Additionally, three derivatives 19, 23 and 26 exhibited rapid bactericidal activity, and remarkable ability to disrupt mature biofilm produced by MRSA USA300. More importantly, a resistant mutant to 19 couldn't be isolated after subjecting MRSA to sub-lethal doses for 14 days. Lastly, this new series of phenylthiazoles possesses an advantageous attribute over the first-generation compounds in their stability to hepatic metabolism, with a biological half-life of more than 9 h. (C) 2018 Elsevier Masson SAS. All rights reserved.