8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes.

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.

• Authors: Matthias Eckhardt, Elke Langkopf, Michael Mark, Moh Tadayyon, Leo Thomas, Herbert Nar, Waldemar Pfrengle, Brian Guth, Ralf Lotz, Peter Sieger, Holger Fuchs, Frank Himmelsbach
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 50 Issue 26 Pg. 6450-3 (Dec 27 2007) ISSN: 0022-2623 [Print] United States
• PMID: 18052023 (Publication Type: Journal Article)

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Hypoglycemic Agents
• Piperidines
• Purines
• Quinazolines
• Linagliptin
• DPP4 protein, human
• Dipeptidyl Peptidase 4

Topics

• Administration, Oral
• Animals
• Caco-2 Cells
• Crystallography, X-Ray
• Diabetes Mellitus, Type 2 (drug therapy)
• Dipeptidyl Peptidase 4
• Dipeptidyl-Peptidase IV Inhibitors
• Dogs
• Humans
• Hypoglycemic Agents (chemical synthesis, pharmacokinetics, pharmacology)
• Linagliptin
• Macaca fascicularis
• Macaca mulatta
• Male
• Models, Molecular
• Piperidines (chemical synthesis, pharmacokinetics, pharmacology)
• Purines (chemical synthesis, pharmacokinetics, pharmacology)
• Quinazolines (chemical synthesis, pharmacokinetics, pharmacology)
• Rats
• Rats, Wistar
• Stereoisomerism
• Structure-Activity Relationship