Studies in potential filaricides. 18. Synthesis of 2,2'-disubstituted 5,5'-dibenzimidazolyl ketones and related compounds as potential anthelmintics.

Abstract

A series of 2,2'-disubstituted 5,5'-dibenzimidazolyl ketones and related compounds have been synthesized of which 2,2'-bis(carbomethoxyamino)-5,5'-dibenzimidazolyl ketone exhibited a broad spectrum of anthelmintic activity in experimental animals. At doses of 10-50 mg/kg given intraperitoneally, 5 killed 100% of the adult worms of Litomosoides carinii, Dipetalonema viteae, and Brugia malayi. By the oral route the macrofilaricidal efficacy of 5 was 97-100% at 100-200 mg/kg X 5 days. The treated animals showed gradual disappearance of microfilariae and before autopsy they became amicrofilariaemic. Some of the compounds also showed 100% efficacy against the 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.