[(1S)-5-amino-1-carboxypentyl]azanium;2-[2-[2-(2,6-dichloroanilino)phenyl]acetyl]oxyacetate | 175391-58-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [(1S)-5-amino-1-carboxypentyl]azanium;2-[2-[2-(2,6-dichloroanilino)phenyl]acetyl]oxyacetate
• CAS: 175391-58-9
• 化学式: C₆H₁₄N₂O₂*C₁₆H₁₃Cl₂NO₄
• 分子量: 500.379
• InChiKey: LOXORQAYVSQDKA-ZSCHJXSPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.38
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  169
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  L-赖氨酸 、 醋氯芬酸 以 乙醇 为溶剂， 反应 3.0h， 生成 [(1S)-5-amino-1-carboxypentyl]azanium;2-[2-[2-(2,6-dichloroanilino)phenyl]acetyl]oxyacetate
  参考文献：
  名称：

  Solubility and Stability Advantage of Aceclofenac Salts

  摘要：

  The nonsteroidal anti-inflammatory drug aceclofenac was screened with pharmaceutically acceptable coformers to discover novel solid forms of improved solubility. First, the X-ray crystal structure of aceclofenac (ACF) was analyzed to contain the rare carboxylic acid catemer O-H center dot center dot center dot O synthon, stabilized by auxiliary C-H center dot center dot center dot O and Cl center dot center dot center dot O interactions. Slurry grinding of aceclofenac with different coformers in a fixed stoichiometry resulted in salts with cytosine (1:1), piperazine (1:0.5), (L)-lysine (1:1), and gamma-aminobutyric acid (1:1). The problem of drug cyclization to give the inactive indolinone byproduct is avoided in the mild conditions of salt formation. All the salts were characterized by spectroscopic methods, thermal analysis, and X-ray diffraction. Aceclofenac-(L)-lysine salt showed 135 times faster intrinsic dissolution rate (IDR) and 127 times higher area under the curve (AUC) compared to aceclofenac. ACF-LYS is a high solubility salt that is stable in the accelerated International Conference on Harmonization (ICH) conditions of 40 degrees C and 75% relative humidity for 8 months.

  DOI：

  10.1021/cg301825u

文献信息

• Solubility and Stability Advantage of Aceclofenac Salts
  作者：N. Rajesh Goud、Kuthuru Suresh、Ashwini Nangia

  DOI：10.1021/cg301825u

  日期：2013.4.3

  The nonsteroidal anti-inflammatory drug aceclofenac was screened with pharmaceutically acceptable coformers to discover novel solid forms of improved solubility. First, the X-ray crystal structure of aceclofenac (ACF) was analyzed to contain the rare carboxylic acid catemer O-H center dot center dot center dot O synthon, stabilized by auxiliary C-H center dot center dot center dot O and Cl center dot center dot center dot O interactions. Slurry grinding of aceclofenac with different coformers in a fixed stoichiometry resulted in salts with cytosine (1:1), piperazine (1:0.5), (L)-lysine (1:1), and gamma-aminobutyric acid (1:1). The problem of drug cyclization to give the inactive indolinone byproduct is avoided in the mild conditions of salt formation. All the salts were characterized by spectroscopic methods, thermal analysis, and X-ray diffraction. Aceclofenac-(L)-lysine salt showed 135 times faster intrinsic dissolution rate (IDR) and 127 times higher area under the curve (AUC) compared to aceclofenac. ACF-LYS is a high solubility salt that is stable in the accelerated International Conference on Harmonization (ICH) conditions of 40 degrees C and 75% relative humidity for 8 months.