Key result
Novel quinazoline compound S-3 selectively inhibits PDE1 in human myocardium while limiting brain exposure.
Why the study?
Potent and selective PDE1 inhibitors with restricted brain access are needed to explore the therapeutic potential of PDE1 inhibition in cardiovascular disease.
Potent and selective periphery-restricted quinazoline inhibitors of PDE1 were discovered, offering new tools to probe PDE1 inhibition in cardiovascular disease.
We disclose the discovery and X-ray cocrystal data of potent, selective quinazoline inhibitors of PDE1. Inhibitor ( S )- 3 readily attains free plasma concentrations above PDE1 IC 50 values and has restricted brain access. The racemic compound 3 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.
No takes yet. Share an insight, caveat, or question.
Humphrey et al. (2018) studied Cardiovascular disease (preclinical). Quinazoline PDE1 inhibitor (S)-3 was evaluated on PDE1B inhibition (IC50). The novel quinazoline compound (S)-3 is a potent and selective periphery-restricted PDE1 inhibitor that limits brain exposure and inhibits cyclic nucleotide hydrolysis in human myocardium.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: