Synthesis and anti-inflammatory activity of phthalimide derivatives, designed as new thalidomide analogues.
This paper describes the synthesis and anti-inflammatory activity of new N-phenyl-phthalimide sulfonamides (3a-e) and the isosters N-phenyl-phthalimide amides (4a-e), designed as hybrids of thalidomide (1) and aryl sulfonamide phosphodiesterase inhibitor (2). In these series, compound 3e (LASSBio 468), having a sulfonyl-thiomorpholine moiety, showed potent inhibitory activity on LPS-induced neutrophil recruitment with ED(50)=2.5mg kg(-1), which was correlated with its inhibitory effect on TNF-alpha level.
Laboratório de Avaliação e Síntese de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Brazil.
Lídia M
LM
Lima
Paulo
P
Castro
Alexandre L
AL
Machado
Carlos Alberto M
CA
Fraga
Claire
C
Lugnier
Vera Lúcia Gonçalves
VL
de Moraes
Eliezer J
EJ
Barreiro
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects; D010797:Phthalimides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013792:Thalidomide / Q000031:analogs & derivatives*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D010797:Phthalimides; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4