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=2.5 mg kg −1, which was correlated with its inhibitory effect on TNF-α level. The synthesis and anti-inflammatory activity of new N-phenyl-phthalimide sulfonamides ( 3a– e) and N-phenyl-phthalimide amides ( 4a– e) are reported. Compound 3e (LASSBio-468), having a sulfonyl-thiomorpholine unit, showed potent inhibitory activity on neutrophil recruitment with ED 50 2.5 mg kg –1, which was correlated with its inhibitory effect on TNF-α level.