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 (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 sam...

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Veröffentlicht in:	Journal of medicinal chemistry 2018-05, Vol.61 (10), p.4635-4640
Hauptverfasser:	Humphrey, John M, Movsesian, Matthew, am Ende, Christopher W, Becker, Stacey L, Chappie, Thomas A, Jenkinson, Stephen, Liras, Jennifer L, Liras, Spiros, Orozco, Christine, Pandit, Jayvardhan, Vajdos, Felix F, Vandeput, Fabrice, Yang, Eddie, Menniti, Frank S
Format:	Artikel
Sprache:	eng
Schlagworte:	Central nervous system Inhibition Inhibitors INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY Peptides and proteins Rodent models
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