Abstract
To obtain selective and potent inhibitors of dipeptidyl peptidases 8 and 9, we synthesized a series of substituted isoindolines as modified analogs of allo-Ile-isoindoline, the reference DPP8/9 inhibitor. The influence of phenyl substituents and different P2 residues on the inhibitors' affinity toward other DPPs and more specifically, their potential to discriminate between DPP8 and DPP9 will be discussed. Within this series compound 8j was shown to be a potent and selective inhibitor of DPP8/9 with low activity toward DPP II.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Chemistry, Pharmaceutical / methods
-
Dipeptidases / antagonists & inhibitors*
-
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors*
-
Drug Design
-
Enzyme Inhibitors / chemical synthesis*
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology*
-
Humans
-
Indoles / chemistry*
-
Inhibitory Concentration 50
-
Lysine / chemistry
-
Models, Chemical
-
Molecular Structure
-
Nitriles / chemistry
-
Peptides / chemistry
-
Stereoisomerism
-
Structure-Activity Relationship
Substances
-
Enzyme Inhibitors
-
Indoles
-
Nitriles
-
Peptides
-
Dipeptidases
-
DPP9 protein, human
-
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
-
DPP8 protein, human
-
Lysine