Synthesis,pharmacokinetics and in vivo antifungal activity of the novel water-soluble prodrugs of itraconazole analogue YL-24  

作　　者：Yu Liu Xu-Feng Cao Xin Liu Yong-Bing Cao Wen-Jing Chu Yu-She Yang 

机构地区：[1]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences [2]School of Pharmacy,Second Military Medical University [3]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medico,Chinese Academy of Sciences

出　　处：《Chinese Chemical Letters》2013年第4期321-324,共4页中国化学快报（英文版）

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)

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.

关 键 词：SynthesisAntifungalWater-soluble prodrugsltraconazole analogue 

分 类 号：TQ460.1[化学工程—制药化工]