On the basis of our previous study, which had demonstrated the strong anthelmintic potential of benzimidazole-2-arylpropenones, we proposed to extend the anthelmintic evaluation by testing anovel series of benzimidazole against Haemonchus contortus. The aimof this work is to appreciate the impact of the bioisoteric replacement of arylpropenone by arylacrylonitrile.Furthermore, we have established the structural elements necessary to get good anthelmintic activities in series of 2-substituted benzimidazoles. The structure-activity relationship studies made after all biological evaluations gathered, revealed that in series benzimidazolyl-phenylpropenones, excellent anthelmintic activities similar to those of Ivermectin have been achieved with the unsubstituted phenyl derivative, with the metahydroxyphenyl derivative, and by replacing the benzene homocycle with a heterocycle like pyridine or furan. Of all the variations made around the benzimidazole heterocycle, it appears that the introduction of a chlorine atom on one of the potential sites of metabolism of benzimidazole (C-5), coupled with the non-substitution of pyrrolic nitrogen, is favorable for obtaining powerful anthelminthic activities superior to those of Ivermectin and similar to those of fenbendazole. The isosteres of the arylpropenone chain, namely arylacrylonitrile and aryl-α-cyanopropenone or even its cyclized derivative (arylcyclohexenone), did not allow the enhancement of anthelmintic activities expected.