The synthesis of a new class of 9-(S)-dihydroerythromycin derivatives and their anti-inflammatory activity on in vivo PMA assay are described. Modifying the desosamine sugar on the C-3' amino group, it was possible to differentiate between anti-biotic and anti-inflammatory action. The compounds are completely devoid of anti-microbial effects but their anti-inflammatory properties are enhanced. These results strongly suggest the potential of macrolides as a new class of anti-inflammatory agents.

This report describes the detailed conformational analysis and synthesis of a series of phthalazine phosphodiesterase-type (IV) (PDE IV) inhibitors bearing either mono- or dichloro 4-methylenepyridine at the 'down' position of the phthalazine nucleus or different heterocycles at the 'top' position 4 of the phthalazine moiety. Both the mono- and dichloro 4-methylenepyridine units linked at carbon C1 of the phthalazine nucleus show identical conformational behaviour with the substituent preferentially oriented towards the external part of the molecule and the pyridine plane almost orthogonal to that of phthalazine ring. The heterocyclic five-membered rings linked at carbon C4 of phthalazine show quite different conformational behaviour. The 1,3-thiazole ring exists in a well-defined conformation almost coplanar with respect to the phthalazine nucleus while the 1,2,4-triazole and the 1,3-diazole heterocycles show a great conformational freedom with large torsion angles. Compound 3 bearing the thiazole ring at C4 displays the major biological activity, thus suggesting that a planar and rather rigid conformation of the pentacycle should favour the PDE IV inhibition capacity of this class of compounds.

This communication describes the synthesis and in vitro evaluation of a novel and potent series of phthalazine phosphodiesterase type (IV) (PDE4) inhibitors. The interaction with two distinct polar binding sites allowed us to eliminate the cyclopentyloxy substitution from rolipram-like analogues.

This communication describes the synthesis and in vitro evaluation of a novel and potent series of phosphodiesterase type IV (PDE4) inhibitors. The compounds described present substituents in position 4 of the phthalazine ring to replace the commonly observed cyclopentyloxy moiety of rolipram analogues. Preliminary evidences of reduced side effects compared to standards and improved pharmacokinetic properties for selected derivatives are also reported.