Sturm P, Cory M, Henry D W
J Med Chem. 1977 Oct;20(10):1333-7. doi: 10.1021/jm00220a021.
3-Aminopyrrolidines bearing acyl substituents on either nitrogen and N-acylated 1,4-diazabicyclo[3.2.1]octanes are potent microfilaricides in the Litomosoides carinii gerbil test system but have no effect on adult worms. The high activity of the pyrrolidine derivatives establishes that diethylcarbamazine (DEC) like antifilarial activity does not require that both pharmacophores be incorporated into one ring. Results with the 1,4-diazabicyclo[3.2.1]octanes establish that an axial conformation of the alkyl substituent corresponding to the equatorial N-methyl group of diethylcarbamazine is fully consistent with high activity. Other conformational consideration pertinent to DEC analogues are discussed.
在氮原子上带有酰基取代基的3-氨基吡咯烷以及N-酰化的1,4-二氮杂双环[3.2.1]辛烷在卡里尼丝虫沙鼠试验系统中是有效的微丝蚴杀虫剂，但对成虫无效。吡咯烷衍生物的高活性表明，像乙胺嗪（DEC）这样的抗丝虫活性并不要求两个药效基团都并入一个环中。1,4-二氮杂双环[3.2.1]辛烷的结果表明，与乙胺嗪的赤道N-甲基相对应的烷基取代基的轴向构象与高活性完全一致。还讨论了与DEC类似物相关的其他构象因素。
