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Bioorg Med Chem Lett. 2008 Sep 15;18(18):5134-9. doi: 10.1016/j.bmcl.2008.07.086. Epub 2008 Jul 24.

Discovery of benzoylpiperazines as a novel class of potent and selective GlyT1 inhibitors.

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  • 1F. Hoffmann-La Roche Ltd, Pharmaceutical Research Basel, Discovery Chemistry, CH-4070 Basel, Switzerland.


Screening of the Roche compound library led to the identification of the benzoylpiperazine 7 as a structurally novel GlyT1 inhibitor. The SAR which was developed in this series resulted in the discovery of highly potent compounds displaying excellent selectivity against the GlyT2 isoform, drug-like properties, and in vivo efficacy after oral administration.

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