Farmer P B, Jarman M, Facchinetti T, Pankiewicz K, Stec W J
Chem Biol Interact. 1977 Jul;18(1):47-57. doi: 10.1016/0009-2797(77)90140-5.
4-Methylcyclophosphamide, an analogue of the antitumour agent cyclophosphamide, exists in cis and trans forms, each of which comprises a pair of optical isomers. The extents of metabolism by rat liver microsomes during 20 min were compared for the four steroisomers incubated separately, and for the racemic cis and trans-derivatives in admixture, using mass spectrometry and gas chromatography respectively. In comparative antitumour tests against the ADJ/PC6 plasma cell tumour in mice, the racemic cis and trans forms of 4- and 6-methylcyclophosphamide had similar therapeutic indices. The four stereoisomers of 4-methylcyclophosphamide exhibited an approx. two-fold range in therapeutic index so that there was no marked effect on either metabolism or antitumour activity occasioned by change of configuration either at C-4 or at phosphorus.
4-甲基环磷酰胺是抗肿瘤药物环磷酰胺的类似物，存在顺式和反式两种形式，每种形式都包含一对光学异构体。分别对四种单独孵育的立体异构体以及混合的外消旋顺式和反式衍生物，利用质谱法和气相色谱法比较了大鼠肝微粒体在20分钟内的代谢程度。在针对小鼠ADJ/PC6浆细胞瘤的比较抗肿瘤试验中，4-甲基和6-甲基环磷酰胺的外消旋顺式和反式形式具有相似的治疗指数。4-甲基环磷酰胺的四种立体异构体的治疗指数显示出约两倍的范围，因此C-4位或磷原子处构型的改变对代谢或抗肿瘤活性均无显著影响。
