Warpehoski M A, Gebhard I, Kelly R C, Krueger W C, Li L H, McGovren J P, Prairie M D, Wicnienski N, Wierenga W
Research Laboratories, Upjohn Company, Kalamazoo, Michigan 49001.
J Med Chem. 1988 Mar;31(3):590-603. doi: 10.1021/jm00398a017.
The synthesis, physicochemical properties, and biological activities of a series of novel spiro cyclopropyl compounds, modeled on the potent antitumor antibiotic CC-1065 (1), are described. Many of these synthetic analogues are significantly more effective than 1 against murine tumors. In particular, compound 27 exhibits high activity and potency. Structure-activity analysis supports a molecular mechanism for biological action involving hydrophobic interaction of the drug with DNA and acid-catalyzed alkylation of DNA.
本文描述了一系列以强效抗肿瘤抗生素CC - 1065（1）为模型的新型螺环丙基化合物的合成、物理化学性质及生物活性。这些合成类似物中的许多对鼠类肿瘤的疗效显著优于1。特别是化合物27表现出高活性和高效能。构效关系分析支持了一种生物作用的分子机制，该机制涉及药物与DNA的疏水相互作用以及DNA的酸催化烷基化。
