Referenced in: none

Automatically associated channels: Kv11.1

Title: Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia.

Authors: Emmanuel Pinard, Alexander Alanine, Daniela Alberati, Markus Bender, Edilio Borroni, Patrick Bourdeaux, Virginie Brom, Serge Burner, Holger Fischer, Dominik Hainzl, Remy Halm, Nicole Hauser, Synèse Jolidon, Judith Lengyel, Hans-Peter Marty, Thierry Meyer, Jean-Luc Moreau, Roland Mory, Robert Narquizian, Mathias Nettekoven, Roger D Norcross, Bernd Puellmann, Philipp Schmid, Sebastien Schmitt, Henri Stalder, Roger Wermuth, Joseph G Wettstein, Daniel Zimmerli

Journal, date & volume: J. Med. Chem., 2010 Jun 24 , 53, 4603-14

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20491477

Abstract
The GlyT1 transporter has emerged as a key novel target for the treatment of schizophrenia. Herein, we report on the optimization of the 2-alkoxy-5-methylsulfonebenzoylpiperazine class of GlyT1 inhibitors to improve hERG channel selectivity and brain penetration. This effort culminated in the discovery of compound 10a (RG1678), the first potent and selective GlyT1 inhibitor to have a beneficial effect in schizophrenic patients in a phase II clinical trial.