title: Synthesis and SAR of azolopyrimidines as potent and selective dipeptidyl peptidase-4 (DPP4) inhibitors for type 2 diabetes.
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.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb, Research and Development, Princeton, NJ 08543-5400, USA. robert.brigance@bms.com
authors.forename: Robert P
authors.initials: RP
authors.lastname: Brigance
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
authors.forename: Aberra
authors.initials: A
authors.lastname: Fura
authors.forename: Thomas
authors.initials: T
authors.lastname: Harrity
authors.forename: Aiying
authors.initials: A
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Zahler
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kirby
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hamann
mesh_terms: 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
chemical_list: D007004:Hypoglycemic Agents; D011480:Protease Inhibitors; D011743:Pyrimidines; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4