| Autor: |
Brian Rago, Vinod D. Parikh, Bruce M. Bechle, Somraj Ghosh, Edelweiss Evrard, Brian M. Campbell, Christine A. Strick, Jamison B. Tuttle, Xinmin Gan, Amy B. Dounay, Kari R. Fonseca, Laura E. Zawadzke, Larry C. James, Jayvardhan Pandit, Michelle A. Salafia, Ji-Young Kim, Laura A. McAllister, Patrick Robert Verhoest, Weldon Horner, Cheng Chang, Marie Anderson |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
ACS Medicinal Chemistry Letters. 4:37-40 |
| ISSN: |
1948-5875 |
| DOI: |
10.1021/ml300237v |
| Popis: |
A series of aryl hydroxamates recently have been disclosed as irreversible inhibitors of kynurenine amino transferase II (KAT II), an enzyme that may play a role in schizophrenia and other psychiatric and neurological disorders. The utilization of structure-activity relationships (SAR) in conjunction with X-ray crystallography led to the discovery of hydroxamate 4, a disubstituted analogue that has a significant potency enhancement due to a novel interaction with KAT II. The use of k inact/K i to assess potency was critical for understanding the SAR in this series and for identifying compounds with improved pharmacodynamic profiles. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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