N,5-bis(4-chlorophenyl)-3-propan-2-yliminophenazin-2-amine;methanesulfonic acid | 1409942-24-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N,5-bis(4-chlorophenyl)-3-propan-2-yliminophenazin-2-amine;methanesulfonic acid
• CAS: 1409942-24-0
• 化学式: CH₄O₃S*C₂₇H₂₂Cl₂N₄
• 分子量: 569.511
• InChiKey: GZPKEXKCPCTJOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.99
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  甲烷磺酸 、 氯苯吩嗪 以 甲醇 、 乙腈 为溶剂， 生成 N,5-bis(4-chlorophenyl)-3-propan-2-yliminophenazin-2-amine;methanesulfonic acid
  参考文献：
  名称：

  Clofazimine Mesylate: A High Solubility Stable Salt

  摘要：

  Clofazimine (CFZ), an antibacterial and anti-inflammatory drug, is also recommended by the World Health Organization for the treatment of leprosy in combination with dapsone and rifampicin. It is an iminophenazine derivative and classified as a Biopharmaceutics Classification System (BCS) class II drug because of poor aqueous solubility (10 mg L-1). Despite it being a very classical drug known for more than five decades, there is no systematic study of CFZ salts for solubility and stability enhancement. We report a solid form screen of CFZ with pharmaceutically acceptable coformers/acids. Salts of CFZ with methanesulfonic acid, maleic acid, isonicotinic acid, nicotinic acid, malonic acid, and salicylic acid in an equimolar ratio as well as an amorphous phase of CFZ are reported. All new solid phases were characterized by FT-IR, powder X-ray diffraction, and differential scanning calorimetry, and confirmed by single crystal X-ray diffraction. The acid proton is transferred to the imine nitrogen of CFZ in a R-2(1)(7) ring motif. The driving force for facile salt formation is the ionic N+-H center dot center dot center dot O- and N-H center dot center dot center dot O(-)bifurcated hydrogen bond synthon. Solubility and powder dissolution experiments were carried out in 60% EtOH-water to compare the higher solubility of salts compared to that of pure CFZ. CFZ-mesylate (1:1) is 99 times more soluble than the pure drug in water. All salts were stable for up to 24 h in 60% EtOH-water slurry medium. CFZ-MSA is the best pharmaceutical salt with high solubility and good stability.

  DOI：

  10.1021/cg301463z

文献信息

• INHALABLE COMPOSITION OF CLOFAZIMINE AND METHODS OF USE
  申请人：Board of Regents, The University of Texas System

  公开号：EP3691646A1

  公开（公告）日：2020-08-12
• COMPOSITIONS OF CLOFAZIMINE, COMBINATIONS COMPRISING THEM, PROCESSES FOR THEIR PREPARATION, USES AND METHODS COMPRISING THEM
  申请人：MannKind Corporation

  公开号：EP3840737A1

  公开（公告）日：2021-06-30
• COMPOSITIONS OF CLOFAZIMINE, COMBINATIONS COMPRISING THEM, PROCESSES FOR THEIR PREPARATION, USES AND METHODS OF TREATMENT COMPRISING THEM
  申请人：MannKind Corporation

  公开号：EP4054524A1

  公开（公告）日：2022-09-14
• INHALABLE COMPOSITION OF CLOFAZIMINE AND METHODS OF USE THEREOF
  申请人：BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM

  公开号：US20200297626A1

  公开（公告）日：2020-09-24

  Provided herein is an inhalable composition of clofazimine. Further provided herein are methods of producing the inhalable clofazimine composition by jet milling. Also provided herein are methods of treating pulmonary diseases by administering the inhalable clofazimine composition.
• [EN] INHALABLE COMPOSITION OF CLOFAZIMINE AND METHODS OF USE<br/>[FR] COMPOSITION À INHALER DE CLOFAZIMINE ET LEURS MÉTHODES D'UTILISATION
  申请人：UNIV TEXAS

  公开号：WO2019070693A1

  公开（公告）日：2019-04-11

  Provided herein is an inhalable composition of clofazimine. Further provided herein are methods of producing the inhalable clofazimine composition by jet milling. Also provided herein are methods of treating pulmonary diseases by administering the inhalable clofazimine composition.