摘要
改进 itraconazole 类似物的水的溶解度，化合物 1 (YL-24 ) ，一系列新奇 prodrugs 被综合。在这些 prodrugs 之中，磷酸盐 disodium 盐混合物在在缓冲区答案的在中立附近的 pH 和足够的稳定性的 7 展出优秀水的溶解度(9.8 mg/mL ) ，与有利 pharmacokinetic 侧面一起。特别地，在鼠科的全身的 Candida albicans SC5314 感染模型加重 1 和 7 提供的中等幸存功效，但是他们的功效比 fluconazole 的弱。
To improve the aqueous solubility of an itraconazole analogue, compound 1 （YL-24）, a series of novel prodrugs were synthesized. Among these prodrugs, the phosphate disodium salt compound 7 exhibited excellent aqueous solubility （9.8 mg/mL） at near-neutral pH and sufficient stability in buffer solutions, along with favorable pharmacokinetic profiles. In particular, compounds 1 and 7 provided moderate survival efficacy in murine systemic Candida albicans SC5314 infection model, but their efficacy was weaker than that of fluconazole.
基金
National Science and Technology Major Project for the support to this research
supported by Key New Drug Creation and Manufacturing Program, China(No.2009ZX09301-001)
