Synthesis and SAR of azolopyrimidines as potent and selective dipeptidyl peptidase-4 (DPP4) inhibitors for type 2 diabetes

Robert P Brigance; Wei Meng; Aberra Fura; Thomas Harrity; Aiying Wang; Robert Zahler; Mark S Kirby; Lawrence G Hamann

doi:10.1016/j.bmcl.2010.06.063

Synthesis and SAR of azolopyrimidines as potent and selective dipeptidyl peptidase-4 (DPP4) inhibitors for type 2 diabetes

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4395-8. doi: 10.1016/j.bmcl.2010.06.063. Epub 2010 Jun 15.

Authors

Robert P Brigance¹, Wei Meng, Aberra Fura, Thomas Harrity, Aiying Wang, Robert Zahler, Mark S Kirby, Lawrence G Hamann

Affiliation

¹ Department of Discovery Chemistry, Bristol-Myers Squibb, Research and Development, Princeton, NJ 08543-5400, USA. [email protected]

PMID: 20598534
DOI: 10.1016/j.bmcl.2010.06.063

Abstract

Several pyrazolo-, triazolo-, and imidazolopyrimidines were synthesized and evaluated as inhibitors of DPP4. Of these three classes of compounds, the imidazolopyrimidines displayed the greatest potency and demonstrated excellent selectivity over the other dipeptidyl peptidases. SAR evaluation for these scaffolds was described as they may represent potential treatments for type 2 diabetes.

MeSH terms

Diabetes Mellitus, Type 2 / drug therapy*
Dipeptidyl Peptidase 4 / metabolism
Humans
Hypoglycemic Agents / chemical synthesis*
Hypoglycemic Agents / chemistry
Hypoglycemic Agents / therapeutic use
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / chemistry
Protease Inhibitors / therapeutic use
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / therapeutic use
Structure-Activity Relationship

Substances

Hypoglycemic Agents
Protease Inhibitors
Pyrimidines
DPP4 protein, human
Dipeptidyl Peptidase 4