Studies in Potential Filaricides. 18. Synthesis of 2,2'-Disubstituted 5,5'-Dibenzimidazolyl Ketones and Related Compounds as Potential Anthelmintics

Article abstract of DOI:10.1021/jm00157a032

A series of 2,2'-disubstituted 5,5'-dibenzimidazolyl ketones (5-8) and related compounds (10-13) have benn synthesized of which 2,2'-bis(carbomethoxyamino>-5,5'-dibenzimidazolyl ketone (5) exhibited a broad spectrum of anthelmintic activity in experimental animals.At doses 10-50 mg/kg given intraperitoneally, 5 killed 100percent of the adult worms of Litomosoides carinii, Dipetalonema viteae, and Brugia malayi.By the oral route the macrofilaricidal efficacy of 5 was 97-100percent at 100-200 mg/kg * 5 days.The treated animals showed gradual disappearance of microfilariae and before autopsy thay became amicrofilariaemic.Some of the compounds (5, 10, 11) also showed 100percent efficacy against human hookworms and tapeworm, Ancylostoma ceylanicum in hamsters, and Hymenolepis nana in rats at a single oral dose of 50-250 mg/kg.Compound 5 was also effective against Syphacia obvelata in mice at a single oral dose of 100 mg/kg and was found to be well tolerated by mice up to an oral dose of 2500 mg/kg.