Cyclic AMP-phosphodiesterases inhibitor improves sodium excretion in rats with cirrhosis and ascites.

Background: The mechanisms responsible for renal dysfunction and sodium retention in cirrhosis remain unclear. Cyclic AMP (cAMP) regulates sodium reabsorption in the proximal nephron. This study investigates the role of cAMP metabolism in renal dysfunction in cirrhosis.

VEGF-induced HUVEC migration and proliferation are decreased by PDE2 and PDE4 inhibitors.

Migration and proliferation of endothelial cells in response to VEGF play an important role in angiogenesis associated to pathologies such as atherosclerosis, diabetes and tumor development. Elevation of cAMP in endothelial cells has been shown to inhibit growth factor-induced proliferation. Our hypothesis was that inactivation of cAMP-specific phosphodiesterases (PDEs) would inhibit angiogenesis.

Design, synthesis and structure-activity relationships of a series of 9-substituted adenine derivatives as selective phosphodiesterase type-4 inhibitors.

Adenine derivatives substituted in position 9 have been demonstrated to have potent cyclic nucleotide phosphodiesterase (PDE) inhibition properties with high selectivity toward PDE-4. Starting from our initial lead compound 9-(2-fluorobenzyl)-N(6)-methyl-2-trifluoromethyladenine (4, NCS613), we designed and synthesized a new series of 9-substituted derivatives for developing structure-activity relationship studies. This new series of derivatives showed increased potencies and better selectivity profiles.