2 research outputs found
Discovery of Potent and Selective Periphery-Restricted Quinazoline Inhibitors of the Cyclic Nucleotide Phosphodiesterase PDE1
We disclose the discovery and X-ray
cocrystal data of potent, selective
quinazoline inhibitors of PDE1. Inhibitor (<i>S</i>)-<b>3</b> readily attains free plasma concentrations above PDE1 IC<sub>50</sub> values and has restricted brain access. The racemic compound <b>3</b> inhibits >75% of PDE hydrolytic activity in soluble samples
of human myocardium, consistent with heightened PDE1 activity in this
tissue. These compounds represent promising new tools to probe the
value of PDE1 inhibition in the treatment of cardiovascular disease
Discovery of Potent and Selective Periphery-Restricted Quinazoline Inhibitors of the Cyclic Nucleotide Phosphodiesterase PDE1
We disclose the discovery and X-ray
cocrystal data of potent, selective
quinazoline inhibitors of PDE1. Inhibitor (<i>S</i>)-<b>3</b> readily attains free plasma concentrations above PDE1 IC<sub>50</sub> values and has restricted brain access. The racemic compound <b>3</b> inhibits >75% of PDE hydrolytic activity in soluble samples
of human myocardium, consistent with heightened PDE1 activity in this
tissue. These compounds represent promising new tools to probe the
value of PDE1 inhibition in the treatment of cardiovascular disease