Novel inhibitors of the high-affinity L-proline transporter as potential therapeutic agents for the treatment of cognitive disorders

Bioorg Med Chem Lett. 2014 Aug 15;24(16):3886-90. doi: 10.1016/j.bmcl.2014.06.049. Epub 2014 Jul 1.

Abstract

The incidence of cognitive disorders such as Alzheimer's disease continues to increase unabated. While cures for such diseases have eluded investigators, progress is being made on alleviating certain symptoms of these diseases. Mouse knockouts of the proline transporter (PROT), a high affinity Na(+)/Cl(-)-dependent transporter, indicated its potential as a novel therapeutic target for cognition improvement. Herein we report our investigation into a novel class of PROT inhibitors.

Keywords: Acyl piperazine; Alzheimer’s disease; Dimentia; Inhibitor; Proline transporter.

MeSH terms

  • Amino Acid Transport Systems, Neutral / antagonists & inhibitors*
  • Amino Acid Transport Systems, Neutral / deficiency
  • Amino Acid Transport Systems, Neutral / metabolism
  • Animals
  • Biological Transport / drug effects
  • Cognition Disorders / drug therapy*
  • Dose-Response Relationship, Drug
  • High-Throughput Screening Assays
  • Humans
  • Mice
  • Mice, Knockout
  • Molecular Structure
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amino Acid Transport Systems, Neutral
  • Small Molecule Libraries
  • proline transport protein