2-[(4-acetylbenzoyl)amino]-4-(pyridin-2-yl)thiazole

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[(4-acetylbenzoyl)amino]-4-(pyridin-2-yl)thiazole
• 英文别名: 4-acetyl-N-[4-(2-pyridinyl)-2-thiazolyl]-benzamide；4-acetyl-N-[4-(2-pyridyl)thiazol-2-yl]benzamide；4-acetyl-N-(4-pyridin-2-yl-1,3-thiazol-2-yl)benzamide
• 化学式: C₁₇H₁₃N₃O₂S
• 分子量: 323.375
• InChiKey: NQYZIUPZVNWRML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-溴-1-(2-吡啶基)-1-乙酮氢溴酸 在 水 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 2-[(4-acetylbenzoyl)amino]-4-(pyridin-2-yl)thiazole
  参考文献：
  名称：

  Structure–activity relationships of 2-aminothiazoles effective against Mycobacterium tuberculosis

  摘要：

  A series of 2-aminothiazoles was synthesized based on a HTS scaffold from a whole-cell screen against Mycobacterium tuberculosis (Mtb). The SAR shows the central thiazole moiety and the 2-pyridyl moiety at C-4 of the thiazole are intolerant to modification. However, the N-2 position of the aminothiazole exhibits high flexibility and we successfully improved the antitubercular activity of the initial hit by more than 128-fold through introduction of substituted benzoyl groups at this position. N-(3-Chlorobenzoyl)-4-(2-pyridinyl)-1,3-thiazol-2-amine (55) emerged as one of the most promising analogues with a MIC of 0.024 mu M or 0.008 mu g/mL in 7H9 media and therapeutic index of nearly similar to 300. However, 55 is rapidly metabolized by human liver microsomes (t(1/2) = 28 min) with metabolism occurring at the invariant aminothiazole moiety and Mtb develops spontaneous low-level resistance with a frequency of similar to 10 (5). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.048

文献信息

• Synthesis and biological evaluation of 2-aminothiazole derivatives as antimycobacterial and antiplasmodial agents
  作者：Faith Mjambili、Mathew Njoroge、Krupa Naran、Carmen De Kock、Peter J. Smith、Valerie Mizrahi、Digby Warner、Kelly Chibale

  DOI：10.1016/j.bmcl.2013.12.022

  日期：2014.1

  A series of compounds derived from the 2-amino-4-(2-pyridyl) thiazole scaffold was synthesized and tested for in vitro antimycobacterial activity against the Mycobacterium tuberculosis H37Rv strain, antiplasmodial activity against the chloroquine sensitive NF54 Plasmodium falciparum strain and cytotoxicity on a mammalian cell line. Optimal antimycobacterial activity was found with compounds with a 2-pyridyl ring at position 4 of the thiazole scaffold, a substituted phenyl ring at the 2-amino position, and an amide linker between the scaffold and the substituted phenyl. The antiplasmodial activity was best with compounds that had the phenyl ring substituted with hydrophobic electron withdrawing groups. (C) 2013 Elsevier Ltd. All rights reserved.
• Structure–activity relationships of 2-aminothiazoles effective against Mycobacterium tuberculosis
  作者：Anja Meissner、Helena I. Boshoff、Mahalakshmi Vasan、Benjamin P. Duckworth、Clifton E. Barry、Courtney C. Aldrich

  DOI：10.1016/j.bmc.2013.08.048

  日期：2013.11

  A series of 2-aminothiazoles was synthesized based on a HTS scaffold from a whole-cell screen against Mycobacterium tuberculosis (Mtb). The SAR shows the central thiazole moiety and the 2-pyridyl moiety at C-4 of the thiazole are intolerant to modification. However, the N-2 position of the aminothiazole exhibits high flexibility and we successfully improved the antitubercular activity of the initial hit by more than 128-fold through introduction of substituted benzoyl groups at this position. N-(3-Chlorobenzoyl)-4-(2-pyridinyl)-1,3-thiazol-2-amine (55) emerged as one of the most promising analogues with a MIC of 0.024 mu M or 0.008 mu g/mL in 7H9 media and therapeutic index of nearly similar to 300. However, 55 is rapidly metabolized by human liver microsomes (t(1/2) = 28 min) with metabolism occurring at the invariant aminothiazole moiety and Mtb develops spontaneous low-level resistance with a frequency of similar to 10 (5). (C) 2013 Elsevier Ltd. All rights reserved.