2. Academic Validation
  3. The design and synthesis of human branched-chain amino acid aminotransferase inhibitors for treatment of neurodegenerative diseases

The design and synthesis of human branched-chain amino acid aminotransferase inhibitors for treatment of neurodegenerative diseases

  • Bioorg Med Chem Lett. 2006 May 1;16(9):2337-40. doi: 10.1016/j.bmcl.2005.07.058.
Lain-Yen Hu 1,  Peter A Boxer,  Suzanne R Kesten,  Huangshu J Lei,  David J Wustrow,  David W Moreland,  Liming Zhang,  Kay Ahn,  Todd R Ryder,  Xiaohong Liu,  John R Rubin,  Kelly Fahnoe,  Richard T Carroll,  Satavisha Dutta,  Douglass C Fahnoe,  Albert W Probert,  Robin L Roof,  Michael F Rafferty,  Catherine R Kostlan,  Jeffrey D Scholten,  Molly Hood,  Xiao-Dan Ren,  Gerald P Schielke,  Ti-Zhi Su,  Charles P Taylor,  Anil Mistry,  Patrick McConnell,  Charles Hasemann,  Jeffrey Ohren
Affiliations

Affiliation

  • 1 Pfizer Global Research and Development, Ann Arbor, MI, USA. Lain-Yen.Hu@pfizer.com
PMID: 16143519 DOI: 10.1016/j.bmcl.2005.07.058
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 microM 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.

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