ONCOGENE-DIRECTED SYNTHESIS--CEPHALOSTATIN CANCER DRUGS

这项建议旨在为人类健康发展计划准备新的合成抗癌剂 最低药效基团生物学定义的目的 头孢他汀类的三环吡嗪家族。五个主要目标 这项为期四年的建议包括： (1)光学活性对称三环吡嗪的合成 类似物具有所有的“上层”螺环酮的功能 头孢他丁1； (2)光学活性对称三环吡嗪的合成 具有低螺酮的所有功能的类似物 头孢菌素1；(3)光学活性不对称化合物的合成 三环吡嗪和吡啶类似物含有所有的 头孢菌素1的两个螺酮的功能性；(4)必需的 这项研究的特点是使用合成的头孢他丁 寻找人类肿瘤亚群的选择性抑制物的类似物 特定的癌基因；(5)体外比较癌基因导向的抗癌作用 用目前的NIH体外60肿瘤专家小组进行药物评估。

This proposal seeks to prepare new synthetic anticancer agents for the purpose of biological definition of the minimum pharmacophore present in the trisdecacyclic pyrazine family of cephalostatins. Five main objectives of this four-year proposal are: (1) Synthesis of optically active symmetrical trisdecacyclic pyrazine analogs bearing all of the functionality of the "upper" spiroketal of cephalostatin 1; (2) Synthesis of optically active symmetrical trisdecacyclic pyrazine analogs bearing all of the functionality of the "lower" spiroketal of cephalostatin 1; and (3) Synthesis of optically active unsymmetrical trisdecacyclic pyrazine and pyridine analogs bearing all of the functionality of both spiroketals of cephalostatin 1; (4) An essential feature of this research features using the synthetic cephalostatin analogs to find selective inhibitors of human tumor subsets caused by particular oncogenes; and (5) Compare in vitro oncogene-guided anticancer agent assessment with the current NIH in vitro 60 tumor panel.