2-amino-N,N-dibenzylthiazole-5-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-amino-N,N-dibenzylthiazole-5-carboxamide
• 英文别名: 2-amino-N,N-dibenzyl-1,3-thiazole-5-carboxamide
• 化学式: C₁₈H₁₇N₃OS
• 分子量: 323.418
• InChiKey: VFCBXZODPPOOGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  87.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基噻唑-5-甲酸 、 二苄胺 在 N-甲基吗啉 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以41%的产率得到2-amino-N,N-dibenzylthiazole-5-carboxamide
  参考文献：
  名称：

  Discovery of the first inhibitors of bacterial enzyme d-aspartate ligase from Enterococcus faecium (Aslfm)

  摘要：

  The D-aspartate ligase of Enterococcus faecium (Asl(fm)) is an attractive target for the development of narrow-spectrum antibacterial agents that are active against multidrug-resistant E. faecium. Although there is currently little available information regarding the structural characteristics of Asl(fm), we exploited the knowledge that this enzyme belongs to the ATP-grasp superfamily to target its ATP binding site. In the first design stage, we synthesized and screened a small library of known ATP-competitive inhibitors of ATP-grasp enzymes. A series of amino-oxazoles derived from bacterial biotin carboxylase inhibitors showed low micromolar activity. The most potent inhibitor compound 12, inhibits Asl(fm) with a K-i value of 2.9 mu M. In the second design stage, a validated ligand-based pharmacophore modeling approach was used, taking the newly available inhibition data of an initial series of compounds into account. Experimental evaluation of the virtual screening hits identified two novel structural types of Asl(fm) inhibitors with 7-amino-9H-purine (18) and 7-amino-1H-pyrazolo[3,4-d]pyrimidine (30 and 34) scaffolds, and also with K-i values in the low micromolar range. Investigation the inhibitors modes of action confirmed that these compounds are competitive with respect to the ATP molecule. The binding of inhibitors to the target enzyme was also studied using isothermal titration calorimetry (ITC). Compounds 6, 12, 18, 30 and 34 represent the first inhibitors of Asl(fm) reported to date, and are an important step forward in combating infections due to E. faecium. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.06.017