Abstract
Two sets of novel analogues of the recently disclosed alpha-keto heterocycle inhibitors of fatty acid amide hydrolase (FAAH), the enzyme responsible for regulation of endogenous oleamide and anandamide, were synthesized and evaluated in order to clarify a role of the electrophilic carbonyl group and structural features important for their activity. Both the electrophilic carbonyl and the degree of alpha-substitution markedly affect inhibitor potency.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amidohydrolases / antagonists & inhibitors*
-
Amidohydrolases / metabolism
-
Animals
-
Arachidonic Acids / pharmacology
-
Cell Membrane / enzymology
-
Endocannabinoids
-
Enzyme Inhibitors / pharmacology
-
Heterocyclic Compounds, 2-Ring / pharmacology*
-
Ketones / pharmacology
-
Kinetics
-
Liver / enzymology
-
Liver / ultrastructure
-
Oleic Acids / pharmacology
-
Polyunsaturated Alkamides
-
Rats
-
Structure-Activity Relationship
Substances
-
Arachidonic Acids
-
Endocannabinoids
-
Enzyme Inhibitors
-
Heterocyclic Compounds, 2-Ring
-
Ketones
-
Oleic Acids
-
Polyunsaturated Alkamides
-
oleylamide
-
Amidohydrolases
-
fatty-acid amide hydrolase
-
anandamide