Lavielle G, Hautefaye P, Schaeffer C, Boutin J A, Cudennec C A, Pierré A
Institut de Recherches Servier, Suresnes, France.
J Med Chem. 1991 Jul;34(7):1998-2003. doi: 10.1021/jm00111a012.
A series of new amino phosphonic acid derivatives of vinblastine (1, VLB) has been synthesized and tested in vitro and in vivo for antitumor activity. The compounds were obtained from O4-deacetyl-VLB azide. All of the new products studied were capable of inhibiting tubulin polymerization in vitro. The most potent antitumor compounds bore an alkyl substituent on the phosphonate. In these compounds, the anti-tumor activity strongly depended on the stereochemistry of the phosphonate. The phosphonate (1S)-[1-[( O4-deacetyl-3-de(methoxycarbonyl)vincaleukoblastin-3-yl] carbonyl]amino]-2-methylpropyl]phosphonic acid diethyl ester exhibited a remarkable activity against cancer cell lines both in vitro and in vivo.
已合成了一系列长春碱（1，VLB）的新型氨基膦酸衍生物，并在体外和体内进行了抗肿瘤活性测试。这些化合物由O4-去乙酰基-VLB叠氮化物制得。所有研究的新产品在体外均能抑制微管蛋白聚合。最有效的抗肿瘤化合物在膦酸酯上带有烷基取代基。在这些化合物中，抗肿瘤活性强烈依赖于膦酸酯的立体化学。膦酸酯（1S）-[1-[(O4-去乙酰基-3-脱（甲氧基羰基）长春新碱-3-基]羰基]氨基]-2-甲基丙基]膦酸二乙酯在体外和体内对癌细胞系均表现出显著活性。
