Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter.

Bollinger SR, Engers DW, Ennis EA, Wright J, Locuson CW, Lindsley CW, Blakely RD, Hopkins CR
Bioorg Med Chem Lett. 2015 25 (8): 1757-1760

PMID: 25801932 · PMCID: PMC4385452 · DOI:10.1016/j.bmcl.2015.02.058

The synthesis and SAR of 4-methoxy-3-(piperidin-4-yl) benzamides identified after a high-throughput screen of the MLPCN library is reported. SAR was explored around the 3-piperidine substituent as well as the amide functionality of the reported compounds. Starting from the initial lead compounds, 1-7, iterative medicinal chemistry efforts led to the identification of ML352 (10m). ML352 represents a potent and selective inhibitor of CHT based on a drug-like scaffold.

Copyright © 2015 Elsevier Ltd. All rights reserved.

MeSH Terms (12)

Animals Benzamides Half-Life HEK293 Cells Humans Membrane Transport Proteins Piperidines Protein Binding Rats Structure-Activity Relationship Symporters Tissue Distribution

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