摘要
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.
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)
