Synthesis and Biological Activity of a Series of Diaryl-Substituted α-Cyano-β-hydroxypropenamides, a New Class of Anthelmintic Agents

Article abstract of DOI:10.1021/jm00115a020

A series of α-cyano-β-hydroxypropenamides was prepared and tested for anthelmintic activity. α-Cyano-β-hydroxy-N-<4-(trifluoromethyl)phenyl>-3-<4-(trifluoromethyl)phenyl>propenamide (1) showed good activity against the nematode Nematospirodes dubius in a mixed parasite infection in mice; several of the analogues were also effective against the cestode Hymenolepis nana.In sheep trials, 1 caused 100percent reduction of the hematophagous nematode Haemonchus contortus after a single dose of 20 mg/kg but did not show satisfactory control of Trichostrongylus colubriformis or Ostertagia circumcincta.Against the liver fluke Fasciola hepatica, 1 suppressed egg production but only temporarily, suggesting that the adult flukes were not eliminated.Mechanism of action studies on 1 using Ascaris mitochondria showed it to be an uncoupler of oxidative phosphorylation.