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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
Author(s) -
Lindsley Craig W.,
Zhao Zhijian,
Leister William H.,
O'Brien Julie,
Lemaire Wei,
Williams David L.,
Chen TsingBau,
Chang Raymond S. L.,
Burno Maryann,
Jacobson Marlene A.,
Sur Cyrille,
Kinney Gene G.,
Pettibone Douglas J.,
Tiller Philip R.,
Smith Sheri,
Tsou Nancy N.,
Duggan Mark E.,
Conn P. Jeffrey,
Hartman George D.
Publication year - 2006
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200600097
Subject(s) - glycine , prepulse inhibition , in vivo , chemistry , dopamine transporter , schizophrenia (object oriented programming) , pharmacology , ex vivo , in vitro , transporter , stereochemistry , computer science , biochemistry , biology , amino acid , programming language , microbiology and biotechnology , gene
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.