title: The design of potent and selective inhibitors of DPP-4: optimization of ADME properties by amide replacements.
abstract: For a series of beta-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes.
authors.affiliation: Santhera Pharmaceuticals (Switzerland) Ltd, Hammerstrasse 47, CH-4410 Liestal, Switzerland. sonja.nordhoff@santhera.com
authors.forename: Sonja
authors.initials: S
authors.lastname: Nordhoff
authors.forename: Stephan
authors.initials: S
authors.lastname: Bulat
authors.forename: Silvia
authors.initials: S
authors.lastname: Cerezo-Gálvez
authors.forename: Oliver
authors.initials: O
authors.lastname: Hill
authors.forename: Barbara
authors.initials: B
authors.lastname: Hoffmann-Enger
authors.forename: Meritxell
authors.initials: M
authors.lastname: López-Canet
authors.forename: Claudia
authors.initials: C
authors.lastname: Rosenbaum
authors.forename: Christian
authors.initials: C
authors.lastname: Rummey
authors.forename: Meinolf
authors.initials: M
authors.lastname: Thiemann
authors.forename: Victor G
authors.initials: VG
authors.lastname: Matassa
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Edwards
authors.forename: Achim
authors.initials: A
authors.lastname: Feurer
mesh_terms: D000577:Amides / Q000037:antagonists & inhibitors / Q000737:chemistry*; D000613:Aminobutyrates / Q000737:chemistry*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000613:Aminobutyrates; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011480:Protease Inhibitors; D015222:Sodium Channels; C014328:2-amino-4-phenylbutyric acid