N'-[(E)-(2-hydroxynaphthalen-1-yl)methylidene]-3-(2-methyl-1H-benzimidazol-1-yl)propanehydrazide | 1443321-11-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N'-[(E)-(2-hydroxynaphthalen-1-yl)methylidene]-3-(2-methyl-1H-benzimidazol-1-yl)propanehydrazide
• 英文别名: Divin；N-[(E)-(2-hydroxynaphthalen-1-yl)methylideneamino]-3-(2-methylbenzimidazol-1-yl)propanamide
• CAS: 1443321-11-6
• 化学式: C₂₂H₂₀N₄O₂
• 分子量: 372.426
• InChiKey: SOPYTFSYTUAGFR-OEAKJJBVSA-N

物化性质

• 密度：
  1.27±0.1 g/cm3(Predicted)
• 溶解度：
  在DMSO中的溶解度为20mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  79.5
• 氢给体数：
  2
• 氢受体数：
  4

制备方法与用途

生物活性

Divin 是一种有效的铁螯合剂，能够有效抑制细菌细胞分裂（bacterial cell division），对革兰氏阴性菌 (Gram-negative bacteria) 和革兰氏阳性菌 (Gram-positive bacteria) 均有抑菌作用。Divin 通过破坏后期分裂蛋白的组装，减少肽聚糖重塑，并阻止细胞质的区室化来发挥作用。

反应信息

• 作为反应物：
  描述：

  N'-[(E)-(2-hydroxynaphthalen-1-yl)methylidene]-3-(2-methyl-1H-benzimidazol-1-yl)propanehydrazide 在 sodium cyanoborohydride 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.5h， 以47%的产率得到N'-[(2-hydroxynaphthalen-1-yl)methyl]-3-(2-methyl-1H-benzimidazol-1-yl)propanehydrazide
  参考文献：
  名称：

  Structure–Activity Studies of Divin: An Inhibitor of Bacterial Cell Division

  摘要：

  We describe the synthesis and structure activity relationship (SAR) studies of divin, a small molecule that blocks bacterial division by perturbing the assembly of proteins at the site of cell septation. The bacteriostatic mechanism of action of divin is distinct from other reported inhibitors of bacterial cell division and provides an opportunity for assessing the therapeutic value of a new class of antimicrobial agents. We demonstrate a convenient synthetic route to divin and its analogues, and describe compounds with a 10-fold increase in solubility and a 4-fold improvement in potency. Divin analogues produce a phenotype that is identical to divin, suggesting that their biological activity comes from a similar mechanism of action. Our studies indicate that the 2-hydroxynaphthalenyl hydrazide portion of divin is essential for its activity and that alterations and substitution to the benzimidazole ring can increase its potency. The SAR study provides a critical opportunity to isolate drug resistant mutants and synthesize photoaffinity probes to determine the cellular target and biomolecular mechanism of divin.

  DOI：

  10.1021/ml400234x
• 作为产物：
  描述：

  2-甲基苯并咪唑 在 potassium carbonate 、 一水合肼 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成 N'-[(E)-(2-hydroxynaphthalen-1-yl)methylidene]-3-(2-methyl-1H-benzimidazol-1-yl)propanehydrazide
  参考文献：
  名称：

  Structure–Activity Studies of Divin: An Inhibitor of Bacterial Cell Division

  摘要：

  We describe the synthesis and structure activity relationship (SAR) studies of divin, a small molecule that blocks bacterial division by perturbing the assembly of proteins at the site of cell septation. The bacteriostatic mechanism of action of divin is distinct from other reported inhibitors of bacterial cell division and provides an opportunity for assessing the therapeutic value of a new class of antimicrobial agents. We demonstrate a convenient synthetic route to divin and its analogues, and describe compounds with a 10-fold increase in solubility and a 4-fold improvement in potency. Divin analogues produce a phenotype that is identical to divin, suggesting that their biological activity comes from a similar mechanism of action. Our studies indicate that the 2-hydroxynaphthalenyl hydrazide portion of divin is essential for its activity and that alterations and substitution to the benzimidazole ring can increase its potency. The SAR study provides a critical opportunity to isolate drug resistant mutants and synthesize photoaffinity probes to determine the cellular target and biomolecular mechanism of divin.

  DOI：

  10.1021/ml400234x

文献信息

• ANTIMICROBIAL COMPOSITIONS AND METHODS OF USE THEREOF
  申请人：Weibel Douglas B.

  公开号：US20130018079A1

  公开（公告）日：2013-01-17

  Described herein is a novel class of inhibitors of bacterial cell division. Several lines of evidence suggest the compounds disclosed herein specifically target the division process and have antibacterial activity in vitro and in vivo. The inhibitors are useful for treating subject in need of treatment for bacterial infections as will as for inhibiting bacterial growth, such as growth on contaminated surfaces.

  本文描述了一类新型的细菌细胞分裂抑制剂。多方证据表明，本文披露的化合物特异地靶向细胞分裂过程，在体外和体内具有抗细菌活性。这些抑制剂可用于治疗需要治疗细菌感染的个体，同时也可用于抑制细菌生长，比如在受污染表面上的生长。
• US9282738B2
  申请人：——

  公开号：US9282738B2

  公开（公告）日：2016-03-15
• Structure–Activity Studies of Divin: An Inhibitor of Bacterial Cell Division
  作者：Maoquan Zhou、Ye-Jin Eun、Ilia A. Guzei、Douglas B. Weibel

  DOI：10.1021/ml400234x

  日期：2013.9.12

  We describe the synthesis and structure activity relationship (SAR) studies of divin, a small molecule that blocks bacterial division by perturbing the assembly of proteins at the site of cell septation. The bacteriostatic mechanism of action of divin is distinct from other reported inhibitors of bacterial cell division and provides an opportunity for assessing the therapeutic value of a new class of antimicrobial agents. We demonstrate a convenient synthetic route to divin and its analogues, and describe compounds with a 10-fold increase in solubility and a 4-fold improvement in potency. Divin analogues produce a phenotype that is identical to divin, suggesting that their biological activity comes from a similar mechanism of action. Our studies indicate that the 2-hydroxynaphthalenyl hydrazide portion of divin is essential for its activity and that alterations and substitution to the benzimidazole ring can increase its potency. The SAR study provides a critical opportunity to isolate drug resistant mutants and synthesize photoaffinity probes to determine the cellular target and biomolecular mechanism of divin.