Delineation of a Fundamental α-Ketoheterocycle Substituent Effect for Use in the Design of Enzyme Inhibitors
- 11 October 2006
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 128 (43) , 14004-14005
- https://doi.org/10.1021/ja064522b
Abstract
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 σp), which relates Ki with the Hammett σp constant of the substituent, the magnitude of the effect (ρ = 3.01), and its predictive value (R2 = 0.91) suggest a widespread applicability in studies beyond FAAH.Keywords
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