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

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 ED50=2.5 mg kg−1, which was correlated with its inhibitory effect on TNF-α level.