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Issue 5, 2017
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Chiral disubstituted piperidinyl ureas: a class of dual diacylglycerol lipase-α and ABHD6 inhibitors

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Abstract

Inhibitors of diacylglycerol lipases and α,β-hydrolase domain containing protein 6 (ABHD6) are potential leads for the development of therapeutic agents for metabolic and neurodegenerative disorders. Here, we report the enantioselective synthesis and structure activity relationships of triazole ureas featuring chiral, hydroxylated 2-benzylpiperidines as dual inhibitors of DAGLα and ABHD6. The chirality of the carbon bearing the C2 substituent, as well as the position of the hydroxyl (tolerated at C5, but not at C3) has profound influence on the inhibitory activity of both DAGLα and ABHD6, as established using biochemical assays and competitive activity-based protein profiling on mouse brain extracts.

Graphical abstract: Chiral disubstituted piperidinyl ureas: a class of dual diacylglycerol lipase-α and ABHD6 inhibitors

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Publication details

The article was received on 16 Jan 2017, accepted on 06 Mar 2017 and first published on 10 Mar 2017


Article type: Research Article
DOI: 10.1039/C7MD00029D
Citation: Med. Chem. Commun., 2017,8, 982-988
  • Open access: Creative Commons BY license
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    Chiral disubstituted piperidinyl ureas: a class of dual diacylglycerol lipase-α and ABHD6 inhibitors

    H. Deng, T. van der Wel, R. J. B. H. N. van den Berg, A. M. C. H. van den Nieuwendijk, F. J. Janssen, M. P. Baggelaar, H. S. Overkleeft and M. van der Stelt, Med. Chem. Commun., 2017, 8, 982
    DOI: 10.1039/C7MD00029D

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