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.
J Med Chem
; 53(12): 4603-14, 2010 Jun 24.
Article
en En
| MEDLINE
| ID: mdl-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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piperazinas
/
Psicotrópicos
/
Esquizofrenia
/
Sulfonas
/
Proteínas de Transporte de Glicina en la Membrana Plasmática
Límite:
Animals
/
Humans
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Male
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Suiza