Document Detail

Delineation of a fundamental alpha-ketoheterocycle substituent effect for use in the design of enzyme inhibitors.
MedLine Citation:
PMID:  17061864     Owner:  NLM     Status:  MEDLINE    
The synthesis and examination of a systematic series of 5-substituted 2-keto oxazoles as inhibitors of fatty acid amide hydrolase (FAAH) defined a fundamental substituent effect that led to the discovery of inhibitors with Ki's as low as 400 pM. The intrinsic basis of the relationship (-log Ki vs sigmap), which relates Ki with the Hammett sigmap constant of the substituent, the magnitude of the effect (rho = 3.01), and its predictive value (R2 = 0.91) suggest a widespread applicability in studies beyond FAAH.
F Anthony Romero; Inkyu Hwang; Dale L Boger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  128     ISSN:  0002-7863     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-25     Completed Date:  2007-09-21     Revised Date:  2010-10-04    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  14004-5     Citation Subset:  IM    
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
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MeSH Terms
Drug Design
Enzyme Inhibitors / chemistry*
Heterocyclic Compounds / chemistry*
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Heterocyclic Compounds

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