Document Report Card

ID: ALA4261499

Journal: Medchemcomm

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

Authors: Deng H, van der Wel T, van den Berg RJBHN, van den Nieuwendijk AMCH, Janssen FJ, Baggelaar MP, Overkleeft HS, van der Stelt M.

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.

CiteXplore: 30108813

DOI: 10.1039/C7MD00029D