Abstract
The synthesis and biochemical evaluation of novel cyanothiazolidine inhibitors of dipeptidyl peptidase 4 (DPP4) is described. Their main structural feature is a constrained bicyclic core that prevents the intramolecular formation of inactive cyclic species. The inhibitors show good to moderate biochemical potency against DPP4 and display distinct selectivity profiles towards DPP7, DPP8 and DPP9 depending on their substitution.
MeSH terms
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Azabicyclo Compounds / chemical synthesis*
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Azabicyclo Compounds / pharmacology
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Catalysis
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Diabetes Mellitus / drug therapy
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Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis*
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Dipeptidyl-Peptidase IV Inhibitors / pharmacology
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Humans
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Inhibitory Concentration 50
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Models, Chemical
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Molecular Structure
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Nitriles / chemical synthesis*
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Nitriles / pharmacology
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Protein Structure, Tertiary
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Pyrrolidines / chemistry
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Structure-Activity Relationship
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Thiazoles / chemistry
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Thiazolidines / chemical synthesis*
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Thiazolidines / pharmacology
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Time Factors
Substances
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Azabicyclo Compounds
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Dipeptidyl-Peptidase IV Inhibitors
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Enzyme Inhibitors
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Nitriles
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Pyrrolidines
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Thiazoles
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Thiazolidines