Communication

Design, Synthesis, and In Vivo Efficacy of Glycine Transporter-1 (GlyT1) Inhibitors Derived from a Series of [4-Phenyl-1-(propylsulfonyl)piperidin-4-yl]methyl Benzamides

  1. Craig W. Lindsley Dr.1,
  2. Zhijian Zhao1,
  3. William H. Leister1,
  4. Julie O'Brien2,
  5. Wei Lemaire2,
  6. David L. Williams Jr. Dr.2,
  7. Tsing-Bau Chen2,
  8. Raymond S. L. Chang Dr.2,
  9. Maryann Burno2,
  10. Marlene A. Jacobson Dr.2,
  11. Cyrille Sur Dr.2,
  12. Gene G. Kinney Dr.2,
  13. Douglas J. Pettibone Dr.2,
  14. Philip R. Tiller Dr.3,
  15. Sheri Smith3,
  16. Nancy N. Tsou4,
  17. Mark E. Duggan1,
  18. P. Jeffrey Conn Dr.2,5,
  19. George D. Hartman1

Article first published online: 29 JUN 2006

DOI: 10.1002/cmdc.200600097

Issue

ChemMedChem

ChemMedChem

Volume 1, Issue 8, pages 807–811, August 11, 2006

Additional Information

How to Cite

Lindsley, Craig W., Zhao, Z., Leister, William H., O'Brien, J., Lemaire, W., Williams, David L., Chen, T.-B., Chang, Raymond S. L., Burno, M., Jacobson, Marlene A., Sur, C., Kinney, Gene G., Pettibone, Douglas J., Tiller, Philip R., Smith, S., Tsou, Nancy N., Duggan, Mark E., Conn, P. Jeffrey. and Hartman, George D. (2006), Design, Synthesis, and In Vivo Efficacy of Glycine Transporter-1 (GlyT1) Inhibitors Derived from a Series of [4-Phenyl-1-(propylsulfonyl)piperidin-4-yl]methyl Benzamides. ChemMedChem, 1: 807–811. doi: 10.1002/cmdc.200600097

Author Information

  1. 1

    Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Merck Research Laboratories, P.O. Box 4, West Point, PA 19486, USA, Fax: (+1) 215-652-6345

  2. 2

    Department of Neuroscience, Merck Research Laboratories, West Point, USA

  3. 3

    Department of Drug Metabolism, Merck Research Laboratories, West Point, USA

  4. 4

    Department of Medicinal Chemistry, X-Ray Crystallography, Rahway, USA

  5. 5

    VICB Program in Drug Discovery, Department of Pharmacology, Vanderbilt, Medical Center, Nashville, TN 37232, USA

Publication History

  1. Issue published online: 3 AUG 2006
  2. Article first published online: 29 JUN 2006
  3. Manuscript Received: 14 APR 2006

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (198K)

Keywords:

  • GlyT1;
  • hypoglutamatergy;
  • NMDA hypofunction;
  • schizophrenia;
  • structure–activity relationships
Thumbnail image of graphical abstract

An iterative analogue library synthesis approach rapidly delivered (S)-13 h, a potent, reversible, and selective GlyT1 inhibitor. (S)-13 h selectively increased glycine levels in the prefrontal cortex to 340 % of basal levels and significantly enhanced prepulse inhibition in mice. Thereby, providing strong support for the development of novel antipsychotics based on the NMDA hypofunction hypothesis of schizophrenia.

View Full Article with Supporting Information (HTML) Get PDF (198K)