Abstract
A series of xanthine mimetics containing 5,5 and 5,6 heterocycle fused imidazoles were synthesized as dipeptidyl peptidase IV inhibitors. Compound 7 is potent (h-DPPIV K(i)=2nM) and exhibits excellent selectivity and no species specificity against rat and human enzymes. The X-ray structure confirms that the binding mode of 7 to rat DPPIV is similar to the parent xanthines.
MeSH terms
-
Animals
-
Dipeptidyl Peptidase 4 / chemistry
-
Dipeptidyl-Peptidase IV Inhibitors*
-
Imidazoles / pharmacology
-
Kinetics
-
Models, Molecular
-
Protease Inhibitors / chemical synthesis
-
Protease Inhibitors / pharmacology*
-
Protein Conformation
-
Rats
-
Structure-Activity Relationship
-
X-Ray Diffraction
-
Xanthines / chemical synthesis
-
Xanthines / pharmacology*
Substances
-
Dipeptidyl-Peptidase IV Inhibitors
-
Imidazoles
-
Protease Inhibitors
-
Xanthines
-
Dipeptidyl Peptidase 4