Designing Co-Crystals of Pharmaceutically Relevant Compounds That Crystallize with Z ' > 1
Designing Co-Crystals of Pharmaceutically Relevant Compounds That Crystallize with Z ' > 1
复制标题
设计 Z > 1 结晶的药物相关化合物的共晶
DOI：
10.1021/cg8009089
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发表时间：
2008
影响因子：
3.8
通讯作者：
Anderson K
中科院分区：
文献类型：
--
作者：
Anderson K
Z ′ > 1时结晶的分子比Z ′ = 1时结晶的纯化合物显示出明显更强的形成共晶的倾向。Z ′ = 1的生物活性化合物形成共晶的比例为4.8%，而Z ′ > 1的化合物在纯态下结晶的比例为7.1%。此外，在整个剑桥结构数据库（CSD）中，形成共晶的不同分子组的Z ′ > 1百分比为17.7%，而有机分子的CSD平均值为11.5%。通过设计和制备奥硝唑（Z′ = 3）与3，5-二硝基苯甲酸的新的1：1共晶，实验证明了这种趋势。预测并制备了两个Z ′ > 1的新的纯结构，即2，3，4-三羟基二苯甲酮和6-苯基-3（2 H）-哒嗪酮。这些化合物分别以Z ′ = 2和3的纯形式结晶。
Molecules which crystallize withZ′ > 1 show a markedly stronger tendency to form co-crystals than compounds that crystallize in the pure form withZ′ = 1. The proportion of bioactive compounds withZ′ = 1 which form co-crystals is 4.8% as opposed to 7.1% for compounds crystallizing withZ′ > 1 in the pure state. Moreover, theZ′ > 1 percentage of the distinct set of molecules in the entire Cambridge Structural Database (CSD) that form co-crystals is 17.7% compared to the CSD average for organic molecules of 11.5%. This tendency is demonstrated experimentally by the design and preparation of a new 1:1 co-crystal of Ornidazole (Z′ = 3 in pure form) with 3,5-dinitrobenzoic acid. Two new pure structures withZ′ > 1 are also predicted and prepared from molecules known to form co-crystals, namely, 2,3,4-trihydroxybenzophenone and 6-phenyl-3(2H)-pyridazinone. These compounds crystallize in their pure form withZ′ = 2 and 3, respectively.