Novel analgesic-antiinflammatory salicylates.

5-(2,4-Difluorophenyl)salicylic acid, diflunisal (25), is the best compound, in terms of both efficacy and safety, from over 500 salicylates investigated in our laboratories. It is a chemically distinct, nonacetylating salicylic acid, more active than aspirin as an analgesic and antiinflammatory agent and superior in duration of action and therapeutic index. Some recent clinical and biochemical observations are briefly discussed.

Discovery of diflunisal.

Diflunisal (MK-647; 5-(2,4-difluorophenyl)-salicylic acid) is a new analgesic anti-inflammatory agent discovered after an extensive chemical and pharmacological study from 1962-71. In the search for a superior salicylate our objectives were higher potency, better tolerance, and a longer duration of action. An evaluation of many available and newly synthesized salicylates, in the granuloma and carrageenan foot oedema assays, revealed the activity-enhancing trend of a hydrophobic group—for example, phenyl, at the carbon-5 position of salicylic acid.