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.
G Greg Zipp  1 ,  Joseph Barbosa  2 ,  Michael A Green  2 ,  Kristen M Terranova  2 ,  Cynthia Fink  2 ,  Xuan-Chuan Yu  3 ,  Amr Nouraldeen  3 ,  Alan Wilson  3 ,  Katerina Savelieva  4 ,  Thomas H Lanthorn  4 ,  S David Kimball  2
Affiliations
  • 1. Department of Medicinal Chemistry, Lexicon Pharmaceuticals, 350 Carter Rd., Princeton, NJ 08540, United States. Electronic address: [email protected].
  • 2. Department of Medicinal Chemistry, Lexicon Pharmaceuticals, 350 Carter Rd., Princeton, NJ 08540, United States.
  • 3. Department of Pharmaceutical Discovery, Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 77381, United States.
  • 4. Department of Neurology, Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 77381, United States.
PMID: 25037917 DOI: 10.1016/j.bmcl.2014.06.049
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.
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