3-(5-chloro-2-methyl-1H-benzimidazol-1-yl)-N'-[(E)-(2-hydroxynaphthalen-1-yl)methylidene]propanehydrazide | 1449030-69-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-(5-chloro-2-methyl-1H-benzimidazol-1-yl)-N'-[(E)-(2-hydroxynaphthalen-1-yl)methylidene]propanehydrazide
• 英文别名: 3-(5-chloro-2-methylbenzimidazol-1-yl)-N-[(E)-(2-hydroxynaphthalen-1-yl)methylideneamino]propanamide
• CAS: 1449030-69-6
• 化学式: C₂₂H₁₉ClN₄O₂
• 分子量: 406.871
• InChiKey: UOGREVPDOVBDRF-ZMOGYAJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 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

反应信息

• 作为产物：
  描述：

  3-(5-chloro-2-methyl-1H-benzimidazol-1-yl)propanehydrazide 、 3-(6-chloro-2-methyl-1H-benzimidazol-1-yl)propanehydrazide 、 2-羟基-1-萘甲醛 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 3-(5-chloro-2-methyl-1H-benzimidazol-1-yl)-N'-[(E)-(2-hydroxynaphthalen-1-yl)methylidene]propanehydrazide 、 3-(6-chloro-2-methyl-1H-benzimidazol-1-yl)-N'-[(E)-(2-hydroxynaphthalen-1-yl)methylidene]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

• 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.