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 (pages 807–811)
Craig W. Lindsley, Zhijian Zhao, William H. Leister, Julie O'Brien, Wei Lemaire, David L. Williams Jr., Tsing-Bau Chen, Raymond S. L. Chang, Maryann Burno, Marlene A. Jacobson, Cyrille Sur, Gene G. Kinney, Douglas J. Pettibone, Philip R. Tiller, Sheri Smith, Nancy N. Tsou, Mark E. Duggan, P. Jeffrey Conn and George D. Hartman
Article first published online: 29 JUN 2006 | DOI: 10.1002/cmdc.200600097
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.