Abstract
A series of diacylethylenediamine derivatives were synthesized and evaluated for their inhibitory activity against DGAT-1 and pharmacokinetic profile to discover new small molecule DGAT-1 inhibitors. Among the compounds, N-[2-({[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]carbonyl}amino)ethyl]-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide 3x showed potent inhibitory activity and excellent PK profile. Oral administration of 3x to mice with dietary-induced obesity resulted in reduced body weight gain and white adipose tissue weight.
Copyright 2010 Elsevier Ltd. All rights reserved.
MeSH terms
-
Animals
-
Baculoviridae / genetics
-
Cell Line
-
Diacylglycerol O-Acyltransferase / antagonists & inhibitors*
-
Enzyme Inhibitors / chemical synthesis*
-
Enzyme Inhibitors / pharmacokinetics
-
Enzyme Inhibitors / pharmacology*
-
Ethylenediamines / chemical synthesis*
-
Ethylenediamines / pharmacokinetics
-
Ethylenediamines / pharmacology*
-
Humans
-
In Vitro Techniques
-
Indicators and Reagents
-
Insecta
-
Mice
-
Microsomes / drug effects
-
Microsomes / enzymology
-
Microsomes, Liver / metabolism
-
Myoblasts / drug effects
-
Myoblasts / enzymology
-
Oxidation-Reduction
-
Rats
-
Structure-Activity Relationship
Substances
-
Enzyme Inhibitors
-
Ethylenediamines
-
Indicators and Reagents
-
Dgat1 protein, rat
-
Diacylglycerol O-Acyltransferase