作者:K.P. Flora、J.C. Cradock、J.A. Kelleyx
DOI:10.1002/jps.2600711106
日期:1982.11
Spirohydantoin mustard (I) is a rationally designed anti-tumor agent with substantial in vivo activity against intracranially implanted tumors in mice. However, hydrolysis of I was much faster than that of mechlorethamine hydrochloride or melphalan, two parenterally administered mustards. The hydrolysis products of I were identified by GC-MS of their silylated derivatives. The decomposition of I (at
螺乙内酰脲芥末(I)是一种经过合理设计的抗肿瘤剂,对小鼠颅内植入的肿瘤具有实质性的体内活性。但是,I的水解比盐酸麦考乙胺或美法仑(两种肠胃外施用的芥末)的水解快得多。I的水解产物通过GC-MS鉴定其甲硅烷基化衍生物。通过GLC监测,I的分解(在25度下于pH 4-6的10%二甲基乙酰胺中)是伪一级反应。I的半衰期在pH 4.0的20分钟到pH 6.0的14分钟的范围内。非离子表面活性剂增强了I的稳定性,但是在较低的pH值下这种作用减弱了,这可能是因为随着更多药物的质子化,I在胶束中的溶解度降低。几种稀释的肠胃外适合的溶剂对I的水解没有显着影响。该药物在10%脂肪乳剂系统中最稳定,其中I的10%分解时间为49 +/- 5分钟。I浓度对时间的曲线是线性的,表明在10%脂肪乳剂体系中消失是零级的。