Chiral disubstituted piperidinyl ureas: a class of dual diacylglycerol lipase-α and ABHD6 inhibitors12. Issue 5 (17th March 2017)

• Record Type: Journal Article
• Authors: Deng, Hui; van der Wel, Tom; van den Berg, Richard J. B. H. N.; van den Nieuwendijk, Adrianus M. C. H.; Janssen, Freek J.; Baggelaar, Marc P.; Overkleeft, Hermen S.; van der Stelt, Mario
• Is Part Of: MedChemComm. Volume 8:Issue 5(2017)
• Page Start: 982
• Page End: 988
• Publication Date: 2017-03-17
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c7md00029d
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : The enantioselective synthesis and structure–activity relationships of deoxy-iminosugar-based triazole ureas as dual inhibitors of DAGLα and ABHD6 were reported. 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.