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Phosphodiesterase 9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of diabetes and Alzheimer's disease. Here we report a potent PDE9 inhibitor 3r that has an IC50 of 0.6 nM and >150-fold selectivity over other PDEs. The HepG2 cell-based assay shows that 3r inhibits the mRNA expression of phosphoenolpyruvate carboxykinase and… (More)
Great attention has been paid to the clinical significance of phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil widely used for erectile dysfunction. However, sildenafil causes side effects on visual functions since it shows similar potencies to inhibit PDE5 and PDE6, whereas tadalafil gives a high selectivity of 1020-fold… (More)
PURPOSE we aimed to investigate the receptor for advanced glycation end products (RAGE) -374T/A polymorphism and breast cancer risk in a Chinese population. METHODS The study subjects included 188 women with histologically confirmed breast cancer and 210 controls. The RAGE genotypes were determined using Polymerase Chain Reaction-Restriction Fragment… (More)
Phosphodiesterase-2A (PDE2A) is a potential therapeutic target for treatment of Alzheimer's disease and pulmonary hypertension. However, most of the current PDE2A inhibitors have moderate selectivity over other PDEs. In the present study, we described the discovery of novel PDE2A inhibitors by structure-based virtual screening combining pharmacophore model… (More)
Phosphodiesterases (PDEs) are the sole enzymes hydrolyzing the important second messengers cGMP and cAMP and have been identified as therapeutic targets for several diseases. The most successful examples are PDE5 inhibitors (i.e., sildenafil and tadalafil), which have been approved for the treatment of male erectile dysfunction and pulmonary hypertension.… (More)
Phosphodiesterase-9A (PDE9A) is a promising therapeutic target for the treatment of diabetes and Alzheimer's disease (AD). The Pfizer PDE9A inhibitor PF-04447943 has completed Phase II clinical trials in subjects with mild to moderate AD in 2013. However, most of the reported PDE9A inhibitors share the same scaffold as pyrazolopyrimidinone, which lacks… (More)
A palladium-catalyzed cascade cross-coupling of N-nitroso-anilines and toluene derivatives for the direct synthesis of N-alkyl-2-aminobenzophenones is described. N-nitroso groups in anilines can act as the traceless directing groups while toluene derivatives can serve as effective acyl precursors under mild reaction conditions.