Discovery of β-homophenylalanine based pyrrolidin-2-ylmethyl amides and sulfonamides as highly potent and selective inhibitors of dipeptidyl peptidase IV
| Autor: | Silvia Cerezo-Galvez, Meinolf Thiemann, Meritxell López-Canet, Holger Deppe, Sonja Nordhoff, Victor G. Matassa, Oliver Hill, Achim Feurer, Christian Rummey, Paul J. Edwards |
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| Rok vydání: | 2009 |
| Předmět: |
Molecular model
medicine.drug_class Stereochemistry Chemistry Pharmaceutical Clinical Biochemistry Pharmaceutical Science Carboxamide Crystallography X-Ray Biochemistry Chemical synthesis Dipeptidyl peptidase Sulfone Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Glucagon-Like Peptide 1 Drug Discovery medicine Animals Molecular Biology Dipeptidyl peptidase-4 chemistry.chemical_classification Dipeptidyl-Peptidase IV Inhibitors Sulfonamides Aminobutyrates Organic Chemistry Hydrogen Bonding Amides Rats Sulfonamide Enzyme chemistry Drug Design Microsomes Liver Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 19:4201-4203 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2009.05.109 |
| Popis: | Modifications of DPP-4 inhibitor 5, that was discovered by structure based design, are described and structure–activity relationships discussed. With analogue 7k one of the most potent non-covalent inhibitors of DPP-4 reported to date (IC50 = 0.38 nM) was discovered. X-ray structure of inhibitor 7k bound to DPP-4 revealed a hydrogen bonding interaction with Q553. First successful efforts in balancing overall properties, as demonstrated by improved metabolic stability, highlight the potential of this series. |
| Databáze: | OpenAIRE |
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