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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2010-6-17
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:AlanineAlexanderA,
pubmed-author:AlberatiDanielaD,
pubmed-author:BenderMarkusM,
pubmed-author:BorroniEdilioE,
pubmed-author:BourdeauxPatrickP,
pubmed-author:BromVirginieV,
pubmed-author:BurnerSergeS,
pubmed-author:FischerHolgerH,
pubmed-author:HainzlDominikD,
pubmed-author:HalmRemyR,
pubmed-author:HauserNicoleN,
pubmed-author:JolidonSyneseS,
pubmed-author:LengyelJudithJ,
pubmed-author:MartyHans-PeterHP,
pubmed-author:MeyerThierryT,
pubmed-author:MoreauJean-LucJL,
pubmed-author:MoryRolandR,
pubmed-author:NarquizianRobertR,
pubmed-author:NettekovenMathiasM,
pubmed-author:NorcrossRoger DRD,
pubmed-author:PinardEmmanuelE,
pubmed-author:PuellmannBerndB,
pubmed-author:SchmidPhilippP,
pubmed-author:SchmittSebastienS,
pubmed-author:StalderHenriH,
pubmed-author:WermuthRogerR,
pubmed-author:WettsteinJoseph GJG,
pubmed-author:ZimmerliDanielD
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pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4603-14
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pubmed:meshHeading |
pubmed-meshheading:20491477-Animals,
pubmed-meshheading:20491477-Brain,
pubmed-meshheading:20491477-CHO Cells,
pubmed-meshheading:20491477-Cricetinae,
pubmed-meshheading:20491477-Cricetulus,
pubmed-meshheading:20491477-Ether-A-Go-Go Potassium Channels,
pubmed-meshheading:20491477-Glycine Plasma Membrane Transport Proteins,
pubmed-meshheading:20491477-Humans,
pubmed-meshheading:20491477-Macaca fascicularis,
pubmed-meshheading:20491477-Male,
pubmed-meshheading:20491477-Mice,
pubmed-meshheading:20491477-Microdialysis,
pubmed-meshheading:20491477-Motor Activity,
pubmed-meshheading:20491477-Patch-Clamp Techniques,
pubmed-meshheading:20491477-Piperazines,
pubmed-meshheading:20491477-Psychotropic Drugs,
pubmed-meshheading:20491477-Rats,
pubmed-meshheading:20491477-Rats, Sprague-Dawley,
pubmed-meshheading:20491477-Schizophrenia,
pubmed-meshheading:20491477-Stereoisomerism,
pubmed-meshheading:20491477-Structure-Activity Relationship,
pubmed-meshheading:20491477-Sulfones
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pubmed:year |
2010
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pubmed:articleTitle |
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.
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pubmed:affiliation |
F. Hoffmann-La Roche Ltd., Pharmaceutical Division, CH-4070 Basel, Switzerland. emmanuel.pinard@roche.com
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pubmed:publicationType |
Journal Article
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