Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres

Douglas J. Sheffler, Michael T. Nedelovych, Richard Williams, Stephen C. Turner, Brittany B. Duerk, Megan R. Robbins, Sataya B. Jadhav, Colleen M. Niswender, Carrie K. Jones, P. Jeffrey Conn, R. Nathan Daniels, Craig W. Lindsley

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]​-​based series, e.g. I, displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was obsd., within this novel series and a no. of other piperidine bioisosteric cores.

Original languageEnglish
Pages (from-to)1062-1066
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number4
Early online date13 Jan 2014
DOIs
Publication statusPublished - 15 Feb 2014

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