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DÉRIVÉS DE TRIAZOLE
专利权人:
F. HOFFMANN-LA ROCHE AG;HOFFMANN-LA ROCHE INC.
发明人:
HOENER, Marius,WICHMANN, Juergen
申请号:
EPEP2016/073589
公开号:
WO2017/060202A1
申请日:
2016.10.04
申请国别(地区):
EP
年份:
2017
代理人:
摘要:
The present invention relates to compounds of formula I; wherein R1' is CH3 R1 is methyl, ethyl, CF3, CH2OH, cyclopropyl or cyano, or R1 and R1 may form together a l,l-dioxo-tetrahydro-thiophen-3-yl ring; R is hydrogen, methyl, ethyl, isopropyl, tert-butyl, cyclopropyl, hydroxmethyl, or 2-propyl- 2-ol; RJ is CI, F, CF3, cyano, methyl, methoxy, isopropyl, or cyclopropyl; R4 is hydrogen, methyl, F or CI; or to a pharmaceutically acceptable salt or acid addition salt, to a racemic mixture, or to its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. The compounds of formula I may be used in the treatment of psychiatric disorders such as schizophrenia, bipolar disorder, obsessive-compulsive disorder or autism spectrum disorder. It has been surprisingly been found that the compounds of general formula I are EAAT3 inhibitors. The excitatory amino acid transporter 3 (EAAT3), also referred to in human studies as solute carrier family 1, member 1 (systematic gene name: SLC1A1) and in rodents as excitatory amino acid carrier 1 (EAAC1), is a high-affinity anionic amino acid transporter found in neurons throughout the cortex and in the hippocampus, basal ganglia (striatum, thalamus), and the olfactory bulb. EAAT3 functions to buffer local glutamate concentrations at excitatory synapses,La présente invention concerne des composés de formule I ; où R1' est CH3, R1 est un méthyle, éthyle, CF3, CH2OH, cyclopropyle ou cyano, ou R1' et R1 peuvent former ensemble un cycle 1,1-dioxo-tétrahydro-thiophén-3-yle ; R est un atome d'hydrogène, un méthyle, éthyle, isopropyle, tert-butyle, cyclopropyle, hydroxyméthyle ou 2-propyl-2-ol ; R3 est Cl, F, CF3, un cyano, méthyle, méthoxy, isopropyle, ou cyclopropyle ; R4 est un atome d'hydrogène, un méthyle, F ou Cl ; ou un sel pharmaceutiquement acceptable ou un sel d'addition d'acide de ceux-ci, un mélange racémique, ou son énantiomère correspondant et/ou un isomère optique et/ou un stéréoisomère de ceux-ci. Les composés d
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