Hilgard P, Brock N
Invest New Drugs. 1984;2(2):131-2. doi: 10.1007/BF00232341.
The "pro-drug" cyclophosphamide (CP) is activated by liver "mixed function" hydroxylases to 4-hydroxy-cyclophosphamide (4-OH-CP), which represents the cytostatically active principle. Since the primary metabolite 4-OH-CP retains all the specific pharmacological properties of the parent compound without the need of metabolic activation, it constituted the basic principle and rationale for further drug development. Due to its chemical instability, 4-OH-CP had to be stabilized through appropriate substitutions at the 4-position of the oxazaphosphorine ring. ASTA Z 7557, in which the side chain is a 2-mercapto-ethanesulfonate, represents the prototype of this new class of oxazaphosphorines.
“前体药物”环磷酰胺（CP）经肝脏“混合功能”羟化酶激活后转化为4-羟基环磷酰胺（4-OH-CP），这是具有细胞抑制活性的成分。由于初级代谢产物4-OH-CP保留了母体化合物的所有特定药理特性，无需代谢激活，它构成了进一步药物研发的基本原理和理论依据。由于其化学不稳定性，4-OH-CP必须通过在恶唑磷环的4位进行适当取代来实现稳定。ASTA Z 7557的侧链为2-巯基乙烷磺酸盐，它代表了这类新型恶唑磷的原型。
