학술논문
Discovery of Potent and Selective Periphery-Restricted Quinazoline Inhibitors of the Cyclic Nucleotide Phosphodiesterase PDE1.
Document Type
Article
Author
Source
Subject
*QUINAZOLINE
*CYCLIC nucleotide phosphodiesterases
*X-rays
*RACEMIC mixtures
*MYOCARDIUM
*CARDIOVASCULAR disease treatment
*
*
*
*
*
Language
ISSN
0022-2623
Abstract
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 IC50 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. [ABSTRACT FROM AUTHOR]