Title of article
The design and synthesis of human branched-chain amino acid aminotransferase inhibitors for treatment of neurodegenerative diseases
Author/Authors
Lain-Yen Hu، نويسنده , , Peter A. Boxer، نويسنده , , Suzanne R. Kesten، نويسنده , , Huangshu J. Lei، نويسنده , , David J. Wustrow، نويسنده , , David W. Moreland، نويسنده , , Liming Zhang، نويسنده , , Kay Ahn، نويسنده , , Todd R. Ryder، نويسنده , , Xiaohong Liu، نويسنده , , John R. Rubin، نويسنده , , Kelly Fahnoe، نويسنده , , Richard T. Carroll، نويسنده , , Satavisha Dutta، نويسنده , , Douglass C. Fahnoe، نويسنده , , Albert W. Probert، نويسنده , , Robin L. Roof، نويسنده , , Michael F. Rafferty، نويسنده , , Catherine R. Kostlan، نويسنده , , Jeffrey D. Scholten، نويسنده , , et al.، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2006
Pages
4
From page
2337
To page
2340
Abstract
The inhibition of the cytosolic isoenzyme BCAT that is expressed specifically in neuronal tissue is likely to be useful for the treatment of neurodegenerative and other neurological disorders where glutamatergic mechanisms are implicated. Compound 2 exhibited an IC50 of 0.8 μM in the hBCATc assays; it is an active and selective inhibitor. Inhibitor 2 also blocked calcium influx into neuronal cells following inhibition of glutamate uptake, and demonstrated neuroprotective efficacy in vivo. SAR, pharmacology, and the crystal structure of hBCATc with inhibitor 2 are described.
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2006
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
796776
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