Synthesis and antiinflammatory evaluation of substituted isophthalonitriles, trimesonitriles, benzonitriles, and terephthalonitriles.
In an effort to develop nonacidic, nonsteroidal, antiinflammatory agents without gastrointestinal complications, a series of cyanobenzenes was synthesized for antiinflammatory evaluation. Twenty-seven substituted isophthalonitriles, 19 trimesonitriles, 30 benzonitriles, and 16 terephthalonitriles were tested in the rat utilizing the carrageenan-induced pedal edema assay. Based on the performance of phenylbutazone in this assay (43.8% reduction at 100 mg/kg), six compounds, dosed at 50 mg/kg, produced reductions in inflammation comparable to this standard. However, the LD50 value of each compound dosed at this level was in the range of 40--56 mg/kg in the mouse; therefore, further the LD50 value of each compound dosed at this level was in the range of 40--56 mg/kg in the mouse; therefore, further study was not warranted. Fifteen compounds possessed activity in excess of 20% reduction at 200 mg/kg and also possessed LD50 values greater than 300 mg/kg. Of these cyanobenzenes, trimesonitrile (16), 4-chlorobenzonitrile, 2-chloroterephthalonitrile, and 2-fluoroterephthalonitrile with reductions in edema of 32, 30, 46, and 49%, respectively, represent the best candidates for subsequent study.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000633:toxicity; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D009570:Nitriles; D002351:Carrageenan