title: Thalidomide analogues: Tumor necrosis factor-alpha inhibitors and their evaluation as anti-inflammatory agents.
abstract: A series of related thalidomide derivatives (2-9) were synthesized by microwave irradiation and evaluated for anti-inflammatory activity. Such activity was assessed in vivo and ex vivo. Compounds 2, 8 and 9 showed the highest levels of inhibition of TNF-α production. On rat paw edema and hyperalgesia assays, compound 9, (1,4-phthalazinedione) demonstrated the highest in vivo anti-inflammatory activity. Thus, compound 9 can be considered as a promising compound to be subjected to further modification to obtain new agents for the treatment of inflammatory diseases.
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113. Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Casal
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113. Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Mariela
authors.initials: M
authors.lastname: Bollini
authors.affiliation: Centro de Investigaciones sobre Porfirias y Porfirinas (CIPYP, UBA-CONICET), Hospital de Clínicas José de San Martín, Avenida Córdoba 2351, 1120. Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: elombardo@qb.fcen.uba.ar.
authors.forename: María Elisa
authors.initials: ME
authors.lastname: Lombardo
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113. Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: anabruno@ffyb.uba.ar.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Bruno
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D005528:Foot / Q000473:pathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D008070:Lipopolysaccharides; D008297:Male; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013792:Thalidomide / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D002351:Carrageenan; D009195:Peroxidase
keywords: Anti-inflammatory effect; Phthalazinone derivate; Phthalimides; TNF-α