Pyridine N-oxides as coformers in the development of drug cocrystals
Pyridine N-oxides as coformers in the development of drug cocrystals
复制标题
DOI：
10.1039/c6ce01838f
复制
发表时间：
2016-10
期刊：
影响因子：
3.1
通讯作者：
B. Saikia;Rajiv Khatioda;Pranita Bora;B. Sarma
中科院分区：
文献类型：
--
作者：
B. Saikia;Rajiv Khatioda;Pranita Bora;B. Sarma
采用简便的方法合成了吡啶n -氧化物，并将其用于药物共晶的制备。与水溶性问题相关的药物，如异丙酚、阿魏酸、磺胺噻唑、对氨基苯甲酸等，被用作具有代表性的活性成分，以设计所需相的药物固体。本研究选择4,4′-联吡啶-N，N′-二氧化氮作为共晶原体。分析了n -氧化物·药物二元体系所表现出的超分子杂合子类型。发现cooh -吡啶n -氧化物、OH或nh -吡啶n -氧化物等氢键合子的形成是稳健的，并遵循晶体结构数据库中观察到的趋势。实验、DFT研究和Hirshfeld表面分析支持了这些合成子与药物性能改善的进一步相关。这一直是药物开发的目标。
Pyridine N-oxides were synthesized via a convenient method and exploited in the preparation of drug cocrystals. Drugs associated with aqueous solubility issues such as propofol, ferulic acid, sulfathiazole, p-aminobenzoic acid etc. were used as the representative active ingredients to engineer pharmaceutical solids of a desired phase. In this study, 4,4′-bipyridine-N,N′-dioxide was picked as the cocrystal former. The types of supramolecular heterosynthons exhibited by the binary systems of N-oxide·drugs were analyzed. The formation of hydrogen bond synthons such as COOH–pyridine N-oxide, OH or NH–pyridine N-oxide was found to be robust and followed the trend observed in the Crystal Structure Database. These synthons were further correlated with the ameliorated properties of the drugs, which was supported by experiments, DFT studies and Hirshfeld surface analysis. This has been a goal in drug development.