title: New fluorinated pyrrolidine and azetidine amides as dipeptidyl peptidase IV inhibitors.
abstract: Cyclohexylglycine amides of various fluorinated pyrrolidines and azetidines were prepared and tested for activity against dipeptidyl peptidase IV and in vivo in the KK mouse model of type 2 diabetes. The tetrafluoropyrrolidide, cis-3,4-difluoropyrrolidide and the fluorinated azetidides displayed unexpectedly strong activity.
authors.affiliation: Pfizer Global Research and Development, Groton, CT 06340, USA. bernard.hulin@pfizer.com
authors.forename: Bernard
authors.initials: B
authors.lastname: Hulin
authors.forename: Shawn
authors.initials: S
authors.lastname: Cabral
authors.forename: Michael G
authors.initials: MG
authors.lastname: Lopaze
authors.forename: Maria A
authors.initials: MA
authors.lastname: Van Volkenburg
authors.forename: Kim M
authors.initials: KM
authors.lastname: Andrews
authors.forename: Janice C
authors.initials: JC
authors.lastname: Parker
mesh_terms: D058892:Adenosine Deaminase Inhibitors; D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001384:Azetidines; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D018819:Dipeptidyl Peptidase 4; D004195:Disease Models, Animal; D005461:Fluorine; D005951:Glucose Tolerance Test; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D051379:Mice; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D058892:Adenosine Deaminase Inhibitors; D000577:Amides; D001384:Azetidines; D006023:Glycoproteins; D011759:Pyrrolidines; D015842:Serine Proteinase Inhibitors; D005461:Fluorine; C082735:azetidine; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4