Antifilarial agents. Diazabicyclooctanes and diazabicycloheptanes as bridged analogs of diethylcarbamazine

Article abstract of DOI:10.1021/jm00251a002

Twelve analogs of diethylcarbamazine (DEC) were prepared by acylation of 3 and 8 methyl 3,8 diazabicyclo[3.2.1]octane, 2 methyl 2,5 diazabicyclo[2.2.2]octane, and 2 methyl 2,5 diazabicyclo[2.2.1]heptane with diethylcarbamyl chloride, ethyl chloroformate, ethyl isocyanate, and cyclohexanecarbonyl chloride. These compounds are formally derived from DEC in possessing two or one carbon bridges over the piperazine ring. When evaluated against Litomosoides carinii in the gerbil, all compounds strongly suppressed blood microfilaremia levels but did not affect the adult worms. Several compounds were nearly equivalent to DEC in activity. The results are discussed in terms of molecular model studies and receptor site theory.