title: Discovery of 3-aminopiperidines as potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitors.
abstract: Substituted 3-aminopiperidines 3 were evaluated as DPP-4 inhibitors. The inhibitors showed good DPP-4 potency with superb selectivity over other peptidases (QPP, DPP8, and DPP9). Selected DPP-4 inhibitors were further evaluated for their hERG potassium channel, calcium channel, Cyp2D6, and pharmacokinetic profiles.
authors.affiliation: Merck Research Laboratories, Department of Medicinal Chemistry, PO Box 2000, Rahway, NJ 07065, USA. jason_cox@merck.com
authors.forename: Jason M
authors.initials: JM
authors.lastname: Cox
authors.forename: Bart
authors.initials: B
authors.lastname: Harper
authors.forename: Anthony
authors.initials: A
authors.lastname: Mastracchio
authors.forename: Barbara
authors.initials: B
authors.lastname: Leiting
authors.forename: Ranabir
authors.initials: R
authors.lastname: Sinha Roy
authors.forename: Reshma A
authors.initials: RA
authors.lastname: Patel
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wu
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lyons
authors.forename: Huaibing
authors.initials: H
authors.lastname: He
authors.forename: Shiyao
authors.initials: S
authors.lastname: Xu
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: Ann E
authors.initials: AE
authors.lastname: Weber
authors.forename: Scott D
authors.initials: SD
authors.lastname: Edmondson
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010880:Piperidines / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010880:Piperidines