Methyl imidazo1,2-bpyridazine-2-carbamates and related compounds as potential antifilarial agents

摘要

A series of imidazo[1,2‐ b ]pyridazines have been synthesized for antifilarial evaluation. The compounds prepared include methyl 6‐benzoylimidazo[1,2‐ b ]pyridazine‐2‐carbamate ( 12 ), 6‐benzoyl‐2‐ t ‐butylimidazo[1,2‐ b ]pyridazine ( 13 ), methyl 6‐(4‐fluorobenzoyl)imidazo[1,2‐ b ]pyridazine‐2‐carbamate ( 14 ), and methyl 6‐(2‐thienylcarbonylcarbonyl)imidazo[1,2‐ b ]pyridazine‐2‐carbamate ( 15 ) which are aza analogs of the anthelmintic agents mebendazole, flubendazole and nocadazole. In addition, the preparation of a series of 2‐ t ‐butylimidazo[1,2‐ b ]‐pyridazine‐6‐carboxylic acid derivatives is described. Electrophilic bromination and iodination substitutions of 2‐ t ‐butyl‐6‐methylimidazo[1,2‐ b ]pyridazine afforded 3‐halo derivatives. Methyl 6‐(4‐fluorobenzoyl)pyridazine‐3‐carbamate was also prepared for antifilarial evaluation. None of these compounds possessed significant antifilarial activity against Brugia pahangi or Acanthocheilonema viteae infections in jirds.