Abstract:
: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.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Tuttle JB,Anderson M,Bechle BM,Campbell BM,Chang C,Dounay AB,Evrard E,Fonseca KR,Gan X,Ghosh S,Horner W,James LC,Kim JY,McAllister LA,Pandit J,Parikh VD,Rago BJ,Salafia MA,Strick CA,Zawadzke LE,Verhoest PRdoi
10.1021/ml300237vsubject
Has Abstractpub_date
2012-10-24 00:00:00pages
37-40issue
1issn
1948-5875journal_volume
4pub_type
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