title: Synthesis, SAR, and atropisomerism of imidazolopyrimidine DPP4 inhibitors.
abstract: The synthesis and SAR of aminomethyl-substituted imidazolopyrimidine DPP4 inhibitors bearing varied pendant aryl groups is described. Compound 1, which exists as a separable mixture of non-interconvertible atropisomers was used as the starting point for investigation. The effects of substituent pattern and type as well as stereochemical effects on inhibitor potency are discussed.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08543-5400, USA. steve.oconnor@bms.com
authors.forename: Stephen P
authors.initials: SP
authors.lastname: O'Connor
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Ligaya M
authors.initials: LM
authors.lastname: Simpkins
authors.forename: Robert P
authors.initials: RP
authors.lastname: Brigance
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
authors.forename: Aiying
authors.initials: A
authors.lastname: Wang
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kirby
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Weigelt
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hamann
mesh_terms: D020134:Catalytic Domain; D004150:Dipeptidases / Q000037:antagonists & inhibitors; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007536:Isomerism; D007700:Kinetics; D008958:Models, Molecular; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D012997:Solvents; D013329:Structure-Activity Relationship
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007093:Imidazoles; D007202:Indicators and Reagents; D011743:Pyrimidines; D012997:Solvents; D004150:Dipeptidases; C471241:DPP9 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C487997:DPP8 protein, human