- 期刊
Synthesis of N-(4-Substituted Phenyl)-2-hydroxynicotinanilides as Potential Anti-inflammatory Agents
並列摘要
Leflunomide 1 and its active metabolite, malononitrilamide (MNA, 2) are clinical use for treating rheumatoid arthritis (RA). Study indicated that the active pharmacophore fully responsible for the immunosuppressive effects of leflunomide metabolite was a β-keto amide with the enolic hydroxyl group leading a salicylamide 3 developed. Currently, we have conducted isosterically structural modification mainly based on salicylamide 3, which β-hydroxy-enamide-containing portion remains untouched, to successfully synthesize 2-hydroxynicotinamides 5-16. After systematic pharmacological screenings, compounds 9 (4-Cl), 10 (4-Br), and 13 (4-NO2) significantly show potent anti-inflammatory activity comparable to leflunomide 1 and malononitrilamide 2 by both in vitro suppressing nitric oxide (NO) production under the LPS-elicited macrophage Raw 264.7 cell and the in-vivo carrageenan-induced paw edema assay.
延伸閱讀
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