Synthesis and SAR of azolopyrimidines as potent and selective dipeptidyl peptidase-4 (DPP4) inhibitors for type 2 diabetes.
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.
Brigance
Robert P
RP
Department of Discovery Chemistry, Bristol-Myers Squibb, Research and Development, Princeton, NJ 08543-5400, USA. robert.brigance@bms.com
Meng
Wei
W
Fura
Aberra
A
Harrity
Thomas
T
Wang
Aiying
A
Zahler
Robert
R
Kirby
Mark S
MS
Hamann
Lawrence G
LG
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D007004:Hypoglycemic Agents; D011480:Protease Inhibitors; D011743:Pyrimidines; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4