Synthesis and biological activity of a series of diaryl-substituted .alpha.-cyano-.beta.-hydroxypropenamides, a new class of anthelmintic agents
| Autor: | Michael A. Rider, Anthony L. Poulton, Eric Brian Sjogren, Richard Komuniecki, Peter H. Nelson, Stanford Bingham, Mark A. Emanuel |
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| Rok vydání: | 1991 |
| Předmět: |
Male
Hymenolepis nana Pharmacology Mice Structure-Activity Relationship chemistry.chemical_compound Nitriles parasitic diseases Drug Discovery medicine Animals Fasciola hepatica Anthelmintic Nematode Infections Anthelmintics Sheep Trifluoromethyl biology Ascaris Biological activity Liver fluke biology.organism_classification Amides chemistry Biochemistry Molecular Medicine Female Haemonchus contortus medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 34:3295-3301 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00115a020 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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