Abstract
A series of racemic and homochiral alpha-aminothiazole-gamma-aminobutyroamides that display high affinities for human and murine CCR2 and functional antagonism by inhibition of monocyte recruitment are described. A representative example is (2S)-2-[2-(acetylamino)-1,3-thiazol-4-yl]-N-[3-methyl-5-(trifluoromethyl)benzyl]-4-(4-phenylpiperidin-1-yl)butanamide, which shows 5 nM affinity for human monocytes and CHO cells expressing the human CCR2b receptor. It also inhibited MCP-1 initiated chemotaxis of human monocytes with an IC50 of 0.69 nM.
MeSH terms
-
Animals
-
CHO Cells
-
Chemokine CCL2 / antagonists & inhibitors
-
Chemokine CCL2 / metabolism
-
Chemotaxis / drug effects
-
Chromatography, High Pressure Liquid
-
Cricetinae
-
Cricetulus
-
Dogs
-
Drug Design
-
Humans
-
In Vitro Techniques
-
Indicators and Reagents
-
Membranes / metabolism
-
Monocytes / drug effects
-
Monocytes / metabolism
-
Neurokinin-1 Receptor Antagonists
-
Rats
-
Rats, Sprague-Dawley
-
Receptors, CCR2
-
Receptors, Chemokine / antagonists & inhibitors*
-
Receptors, Chemokine / drug effects
-
Stereoisomerism
-
Structure-Activity Relationship
Substances
-
CCL2 protein, human
-
CCR2 protein, human
-
Ccr2 protein, rat
-
Chemokine CCL2
-
Indicators and Reagents
-
Neurokinin-1 Receptor Antagonists
-
Receptors, CCR2
-
Receptors, Chemokine