Ludeman S M
Duke Comprehensive Cancer Center and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Curr Pharm Des. 1999 Aug;5(8):627-43.
This is primarily an overview of the spontaneous (non-enzymatic) chemistry of the metabolites of cyclophosphamide, viz., cis- and trans-4-hydroxycyclophosphamide, aldophosphamide (and its hydrate), iminophosphamide, phosphoramide mustard, acrolein, and chloroethylaziridine. A brief description of detoxification products obtained through enzyme catalyzed reactions appears. Included as the historical basis for the development of cyclophosphamide is the chemistry of nitrogen mustards. Among the topics covered are: perturbations to metabolite distributions and half-lives effected by buffer, structure, pH and nucleophiles; effects of pH on mechanism; alkylation versus P-N bond hydrolysis; the influence of nucleophiles on alkylation product distributions; the influence of substituents on alkylation rates; and preactivated forms of cyclophosphamide as metabolite precursors (4-hydroperoxycyclophosphamide and mafosfamide). A review with 66 references.
本文主要概述了环磷酰胺代谢产物的自发（非酶促）化学性质，即顺式和反式4-羟基环磷酰胺、醛磷酰胺（及其水合物）、亚氨基磷酰胺、磷酰胺氮芥、丙烯醛和氯乙基亚胺。文中还简要描述了通过酶催化反应获得的解毒产物。作为环磷酰胺发展的历史基础，文中介绍了氮芥的化学性质。涵盖的主题包括：缓冲液、结构、pH值和亲核试剂对代谢产物分布和半衰期的影响；pH值对反应机制的影响；烷基化与P-N键水解；亲核试剂对烷基化产物分布的影响；取代基对烷基化速率的影响；以及作为代谢产物前体的环磷酰胺预活化形式（4-氢过氧化环磷酰胺和马磷酰胺）。附有66篇参考文献的综述。
