title: From lead to preclinical candidate: optimization of beta-homophenylalanine based inhibitors of dipeptidyl peptidase IV.
abstract: A series of highly potent and selective inhibitors of DPP-4 was optimized for ADMET properties. The effort resulted in the discovery of inhibitor 1g, that exhibits excellent efficacy in an oral glucose tolerance test and an attractive pharmacokinetic profile.
authors: Santhera Pharmaceuticals (Switzerland) Ltd, Hammerstrasse 47, CH-4410 Liestal, Switzerland. sonja.nordhoff@santhera.com
authors: Sonja
authors: S
authors: Nordhoff
authors: Meritxell
authors: M
authors: López-Canet
authors: Barbara
authors: B
authors: Hoffmann-Enger
authors: Stephan
authors: S
authors: Bulat
authors: Silvia
authors: S
authors: Cerezo-Gálvez
authors: Oliver
authors: O
authors: Hill
authors: Claudia
authors: C
authors: Rosenbaum
authors: Christian
authors: C
authors: Rummey
authors: Meinolf
authors: M
authors: Thiemann
authors: Victor G
authors: VG
authors: Matassa
authors: Paul J
authors: PJ
authors: Edwards
authors: Achim
authors: A
authors: Feurer
mesh_terms: D000284:Administration, Oral; D000613:Aminobutyrates / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004285:Dogs; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000613:Aminobutyrates; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006845:Hydrocarbons, Fluorinated; D007004:Hypoglycemic Agents; D011480:Protease Inhibitors; D011759:Pyrrolidines; C014328:2-amino-4-phenylbutyric acid; D018819:Dipeptidyl Peptidase 4