Synthesis and anti-inflammatory activity of phthalimide derivatives, designed as new thalidomide analogues

Bioorg Med Chem. 2002 Sep;10(9):3067-73. doi: 10.1016/s0968-0896(02)00152-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / pharmacology
  • Bronchoalveolar Lavage Fluid
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Dose-Response Relationship, Drug
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neutrophil Infiltration / drug effects
  • Phthalimides / chemical synthesis*
  • Phthalimides / pharmacology
  • Structure-Activity Relationship
  • Thalidomide / analogs & derivatives*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • Phthalimides
  • Tumor Necrosis Factor-alpha
  • Thalidomide
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Cyclic Nucleotide Phosphodiesterases, Type 4