Niclosamide-p-aminobenzoic acid | 1392401-09-0

• 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: Niclosamide-p-aminobenzoic acid
• 英文别名: 4-aminobenzoic acid;5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide
• CAS: 1392401-09-0
• 化学式: C₇H₇NO₂*C₁₃H₈Cl₂N₂O₄
• 分子量: 464.262
• InChiKey: YBYGQTZELIKTQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.83
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  159
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  氯硝柳胺 、 对氨基苯甲酸 以 乙酸乙酯 为溶剂， 反应 0.25h， 生成 Niclosamide-p-aminobenzoic acid
  参考文献：
  名称：

  Pharmaceutical Cocrystals of Niclosamide

  摘要：

  Niclosamide (NCL) is an anthelmintic BCS class II drug of low solubility and high permeability. Pharmaceutical cocrystals of NCL were prepared with GRAS molecules, such as caffeine (CAF), urea (URE), p-aminobenzoic acid (PABA), theophylline (THPH), nicotinamide (NCT), and isonicotinamide (INA), to improve drug solubility. Neat grinding, wet granulation, and slow evaporation methods were successful to make niclosamide cocrystals. All new crystalline forms were characterized by X-ray diffraction, differential scanning calorimetry, and IR-Raman spectroscopy to confirm their purity and homogeneity. X-ray crystal structures provided details of hydrogen bonding, molecular packing, and drug...coformer interactions. The intermolecular O-H center dot center dot center dot O hydrogen bond from the hydroxyl donor to the carbonyl acceptor in the niclosamide crystal structure was replaced by an acceptor atom of the coformer in cocrystal structures. Cocrystals with nicotinamide and isonicotinamide were characterized by C-13 ss-NMR spectroscopy because their single crystals could not be obtained. All cocrystals, except NCL-PABA, showed a faster powder dissolution rate than the reference active pharmaceutical ingredient (API). Niclosamide theophylline acetonitrile solvate showed the highest solubility (6 times compared to the API) among all the crystalline forms. NCL-THPH cocrystals showed comparably good dissolution (5 times faster than the drug) up to 90 min. The solubility advantage of the cocrystal was diminished by transformation to insoluble niclosamide monohydrate within 1 h of the dissolution experiment in 40% i-PrOH-water. Equilibrium solubility experiments showed that all cocrystals as well as the pure API transformed to NCL monohydrate within 24 h in 40% i-PrOH-water slurry medium. Among the cocrystals studied, NCL-NCT and NCL-INA exhibited better stability under accelerated humidity conditions (75% RH, 40 degrees C), but they did not have the same solubility advantage as the fast dissolving species NCL THPH.

  DOI：

  10.1021/cg300784v