Abstract
A new chemical class of potent DPP-4 inhibitors structurally derived from the xanthine scaffold for the treatment of type 2 diabetes has been discovered and evaluated. Systematic structural variations have led to 1 (BI 1356), a highly potent, selective, long-acting, and orally active DPP-4 inhibitor that shows considerable blood glucose lowering in different animal species. 1 is currently undergoing clinical phase IIb trials and holds the potential for once-daily treatment of type 2 diabetics.
MeSH terms
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Administration, Oral
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Animals
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Caco-2 Cells
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Crystallography, X-Ray
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Diabetes Mellitus, Type 2 / drug therapy*
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Dipeptidyl Peptidase 4
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Dipeptidyl-Peptidase IV Inhibitors*
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Dogs
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Humans
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Hypoglycemic Agents / chemical synthesis*
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Hypoglycemic Agents / pharmacokinetics
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Hypoglycemic Agents / pharmacology
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Linagliptin
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Macaca fascicularis
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Macaca mulatta
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Male
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Models, Molecular
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Piperidines / chemical synthesis*
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Piperidines / pharmacokinetics
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Piperidines / pharmacology
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Purines / chemical synthesis*
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Purines / pharmacokinetics
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Purines / pharmacology
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Quinazolines / chemical synthesis*
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Quinazolines / pharmacokinetics
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Quinazolines / pharmacology
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Rats
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Rats, Wistar
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Dipeptidyl-Peptidase IV Inhibitors
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Hypoglycemic Agents
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Piperidines
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Purines
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Quinazolines
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Linagliptin
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DPP4 protein, human
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Dipeptidyl Peptidase 4