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ID: ALA1159083

Journal: Bioorg Med Chem Lett

Title: An octahydro-cyclopenta[c]pyrrole series of inhibitors of the type 1 glycine transporter.

Authors: Lowe JA, Deninno SL, Drozda SE, Schmidt CJ, Ward KM, David Tingley F, Sanner M, Tunucci D, Valentine J.

Abstract: We describe a novel series of inhibitors of the type 1 glycine transporter (GlyT1) as an approach to relieving the glutamatergic deficit that is thought to underlie schizophrenia. Synthesis and SAR follow-up of a series of octahydro-cyclopenta[c]pyrrole derivatives afforded potent in vitro inhibition of GlyT1 as well as in vivo activity in elevating CSF glycine. We also found that a 3-O(c-pentyl), 4-F substituent may serve as a surrogate for the widely used 3-trifluoromethoxy group, suggesting its application as an isostere for future medicinal chemistry studies.

CiteXplore: 20045321

DOI: 10.1016/j.bmcl.2009.12.071