tomoxiprole and Stomach-Ulcer

Novel 3-alkyl-2-aryl-3H- naphth [1,2-d]imidazoles were synthesized and evaluated as antiinflammatory agents in the carrageenin-induced paw edema, cotton pellet induced granuloma, and adjuvant-induced polyarthritis assays in rats. The analgesic, antipyretic, and gastroulcerogenic effects were also tested. Structure-activity relationships are discussed. One of the compounds, 3-(1-methylethyl)-2-(4-methoxyphenyl)-3H- naphth [1,2-d]imidazole (35), was selected for clinical trials as a nonacidic antiinflammatory and analgesic agent.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Drug Evaluation, Preclinical; Edema; Granuloma; Imidazoles; Indicators and Reagents; Male; Naphthalenes; Pain; Rats; Stomach Ulcer; Structure-Activity Relationship

The effects of 3-(1-methylethyl)-2-(4-methoxyphenyl)-3H-naphth [1,2-d]imidazole, MDL 035, a new non-steroidal non-acidic anti-inflammatory compound, on the production of prostaglandin (PG) in rat gastric mucosa in vivo and in vitro and in inflammatory exudate in vivo were studied. MDL 035 reduced PGE2 and 6-keto-PGF1 alpha levels more effectively in inflamed tissue than in gastric mucosa when assayed in in vivo experiments, whereas indomethacin and other non-steroidal anti-inflammatory drugs (NSAIDS) are equally effective in both systems. MDL 035 is almost as active as indomethacin when incubated with gastric tissue in vitro. The better gastric tolerance of MDL 035 than of other NSAIDS is discussed in relation to these differences in in vivo and in vitro effects.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Dinoprostone; Dose-Response Relationship, Drug; Exudates and Transudates; Gastric Mucosa; Imidazoles; In Vitro Techniques; Indomethacin; Inflammation; Male; Naproxen; Prostaglandins; Prostaglandins E; Rats; Stomach Ulcer