title: Synthesis and biological activity of a series of diaryl-substituted alpha-cyano-beta-hydroxypropenamides, a new class of anthelmintic agents.
abstract: A series of alpha-cyano-beta-hydroxypropenamides was prepared and tested for anthelmintic activity. alpha-Cyano-beta-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 100% 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.
authors.affiliation: Syntex Research, Palo Alto, California 94304.
authors.forename: E B
authors.initials: EB
authors.lastname: Sjogren
authors.forename: M A
authors.initials: MA
authors.lastname: Rider
authors.forename: P H
authors.initials: PH
authors.lastname: Nelson
authors.forename: S
authors.initials: S
authors.lastname: Bingham
authors.forename: A L
authors.initials: AL
authors.lastname: Poulton
authors.forename: M A
authors.initials: MA
authors.lastname: Emanuel
authors.forename: R
authors.initials: R
authors.lastname: Komuniecki
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000627:therapeutic use; D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis* / Q000627:therapeutic use; D005260:Female; D008297:Male; D051379:Mice; D009349:Nematode Infections / Q000188:drug therapy; D009570:Nitriles / Q000138:chemical synthesis* / Q000627:therapeutic use; D012756:Sheep; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000871:Anthelmintics; D009570:Nitriles; C071839:alpaha-cyano-beta-hydroxy-N-(4-(trifluoromethyl)phenyl)-3-(4-(trifluoromethyl)phenyl)propenamide