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Updated: Jul 14, 2026

Novel Object Recognition Test for the Investigation of Learning and Memory in Mice
Published on: August 30, 2017
Discovery of Selective Phosphodiesterase 1 Inhibitors with Memory Enhancing Properties
Brian Dyck1, Bryan Branstetter1, Tawfik Gharbaoui1
1Dart Neuroscience LLC , 12278 Scripps Summit Drive, San Diego, California 92131, United States.
Abstract:
A series of potent thienotriazolopyrimidinone-based PDE1 inhibitors was discovered. X-ray crystal structures of example compounds from this series in complex with the catalytic domain of PDE1B and PDE10A were determined, allowing optimization of PDE1B potency and PDE selectivity. Reduction of hERG affinity led to greater than a 3000-fold selectivity for PDE1B over hERG. 6-(4-Methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4',3':4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one was identified as an orally bioavailable and brain penetrating PDE1B enzyme inhibitor with potent memory-enhancing effects in a rat model of object recognition memory.
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