Bulky amine analogues of ketoprofen: potent antiinflammatory agents.
Replacement of the carboxyl group of 2-(3-benzoylphenyl)propionic acid (Ketoprofen) with various bulky amines has produced a series of highly active antiinflammatory agents that have reduced intestinal ulcerogenicity and have better therapeutic ratios in the 21-day adjuvant arthritis assay in rats than currently marketed nonsteroidal antiinflammatory drugs. Activity is maintained on reduction of these 2-(3-benzoylphenyl)propyl bulky amines to the corresponding alcohols or methylene analogues, on conversion of the ketone function to a primary amine or oxime, and on introduction of a 4-halo substitutent (Cl or F) on the terminal aromatic ring. Removal of the alpha-CH3 group greatly reduces the antiinflammatory activity of the series. These compounds have been synthesized by the reductive amination of 2-(3-bromophenyl)propionaldehyde with the respective amine followed by lithiation of this product and condensation with the appropriate benzonitrile.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis*; D001169:Arthritis, Experimental / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000188:drug therapy; D007202:Indicators and Reagents; D007660:Ketoprofen / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010666:Phenylpropionates / Q000138:chemical synthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D007202:Indicators and Reagents; D010666:Phenylpropionates; D007660:Ketoprofen