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作为对环磷酰胺结构改造新思路的延续, 本文以化合物9i为先导物设计并合成了三个系列环磷酰胺哌嗪季铵盐类衍生物(10, 11和13)。通过体内抗肿瘤活性试验, 其构效关系表明: 1)环磷酰胺螺环哌嗪季铵盐(10)的构象和N-3位的取代基对活性影响极大2)不同类型的环磷酰胺非螺环哌嗪季铵盐(11)显示出其抗肿瘤活性的差异 3) 选择合适的季铵盐部分, 化合物1,2-苯并异恶唑磷酰哌嗪季铵盐(13)有可能具有抗肿瘤活性。此研究结果将有助于进一步设计和改造各种氮芥类抗肿瘤药物。
As a continuation of the new idea of structural modification of cyclophosphamide, three series of cyclophosphamide piperazine quaternary ammonium salt derivatives (10, 11 and 13) were designed and synthesized using compound 9i as the lead. Through the in vivo antitumor activity test, the structure-activity relationship shows that: 1) the conformation of the cyclosporin spiropiperazine quaternary ammonium salt (10) and the substituent at the N-3 position have a great effect on the activity; 2) different types of cyclophosphamide The amide non-spiro piperazine quaternary ammonium salt (11) shows a difference in antitumor activity. 3) Selecting the appropriate quaternary ammonium salt moiety, the compound 1,2-benzisoxazolylphosphono piperazine quaternary salt (13) It is possible to have anti-tumor activity. The results of this study will help to further design and transform a variety of nitrogen mustard antitumor drugs.