2,2'-oxybis(N'-(4-fluorobenzylidene)acetohydrazide)

• 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: 2,2'-oxybis(N'-(4-fluorobenzylidene)acetohydrazide)
• 英文别名: N-[(4-fluorophenyl)methylideneamino]-2-[2-[2-[(4-fluorophenyl)methylidene]hydrazinyl]-2-oxoethoxy]acetamide
• 化学式: C₁₈H₁₆F₂N₄O₃
• 分子量: 374.347
• InChiKey: DBMSAJGREJZRAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  92.2
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-(2-肼基-2-氧代乙氧基)乙酰肼 、 对氟苯甲醛 以 乙醇 为溶剂， 生成 2,2'-oxybis(N'-(4-fluorobenzylidene)acetohydrazide)
  参考文献：
  名称：

  Design and Development of Mycobacterium tuberculosis Lysine ɛ ‐Aminotransferase Inhibitors for Latent Tuberculosis Infection

  摘要：

  Lysine ɛ‐aminotransferase (LAT) is a protein involved in lysine catabolism, and it plays a significant role during the persistent/latent phase of Mycobacterium tuberculosis (MTB), as observed by its up‐regulation by ~40‐fold during this stage. We have used the crystal structure of MTB LAT in external aldimine form in complex with its substrate lysine as a template to design and identify seven lead compounds with IC50 ranging from 18.06 to > 90 μm. We have synthesized 21 compounds based on the identified lead, and compound 21 [2,2′‐oxybis(N′‐(4‐fluorobenzylidene)acetohydrazide)] was found to be the most active with MTB LAT IC50 of 0.81 ± 0.03 μm. Compound 21 also showed a 2.3 log reduction in the nutrient‐starved MTB model and was more potent than standard isoniazid and rifampicin at the same dose level of 10 μg/mL.

  DOI：

  10.1111/cbdd.12655

文献信息

• Design and Development of <i>Mycobacterium tuberculosis</i> Lysine <i>ɛ</i> ‐Aminotransferase Inhibitors for Latent Tuberculosis Infection
  作者：Brindha Devi Parthiban、Shalini Saxena、Manoj Chandran、Padma Sridevi Jonnalagadda、Renu Yadav、Rudraraju Reshma Srilakshmi、Yogeeswari Perumal、Sriram Dharmarajan

  DOI：10.1111/cbdd.12655

  日期：2016.2

  Lysine ɛ‐aminotransferase (LAT) is a protein involved in lysine catabolism, and it plays a significant role during the persistent/latent phase of Mycobacterium tuberculosis (MTB), as observed by its up‐regulation by ~40‐fold during this stage. We have used the crystal structure of MTB LAT in external aldimine form in complex with its substrate lysine as a template to design and identify seven lead compounds with IC50 ranging from 18.06 to > 90 μm. We have synthesized 21 compounds based on the identified lead, and compound 21 [2,2′‐oxybis(N′‐(4‐fluorobenzylidene)acetohydrazide)] was found to be the most active with MTB LAT IC50 of 0.81 ± 0.03 μm. Compound 21 also showed a 2.3 log reduction in the nutrient‐starved MTB model and was more potent than standard isoniazid and rifampicin at the same dose level of 10 μg/mL.