McCall J W, Ziegler J B
J Med Chem. 1977 Oct;20(10):1327-33. doi: 10.1021/jm00220a020.
cis-and trans-1,2-cyclobutanediamines bearing appropriate N-methyl and N-acyl substituents were prepared as analogues of diethylcarbamazine (DEC). None displayed activity against Litomosoides carinii in the gerbil despite substantial structural and sterochemical similarities to the parent drug. The inactivity of these drugs is rationalized in terms of eclipsed pharmacophore configurations and the increased population of unfavorable rotational conformations made possible by the exocyclic position of both pharmacophores. To provide perspective for these conclusions, the literature on DEC analogues is briefly summarized and structure-activity data are discussed in terms of critical structural factors associated with microfilaricidal activity. Generalizations on structural principles governing activity are advanced which encompass test results for the large majority of DEC analogues.
制备了带有合适的N-甲基和N-酰基取代基的顺式和反式-1,2-环丁二胺作为乙胺嗪（DEC）的类似物。尽管这些类似物与母体药物在结构和立体化学上有很大相似性，但在沙鼠中对卡里尼丝虫均无活性。这些药物的无活性可根据重叠的药效团构型以及两个药效团的环外位置所导致的不利旋转构象数量增加来解释。为了给这些结论提供背景，简要总结了关于DEC类似物的文献，并根据与微丝蚴杀灭活性相关的关键结构因素讨论了构效关系数据。提出了关于控制活性的结构原理的概括，其中涵盖了绝大多数DEC类似物的测试结果。
