title: Synthesis and evaluation of [(1R)-1-amino-2-(2,5-difluorophenyl)ethyl]cyclohexanes and 4-[(1R)-1-amino-2-(2,5-difluorophenyl)ethyl]piperidines as DPP-4 inhibitors.
abstract: A series of 4-amino cyclohexanes and 4-substituted piperidines were prepared and evaluated for inhibition of DPP-4. Analog 20q displayed both good DPP-4 potency and selectivity against other proteases, while derivative 20k displayed long half life and modest oral bioavailability in rat. The most potent analog, 3-(5-aminocarbonylpyridyl piperidine 53j, displayed excellent DPP-4 activity with good selectivity versus other proline enzymes.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. ping_chen@merck.com
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Charles G
authors.initials: CG
authors.lastname: Caldwell
authors.forename: Wallace
authors.initials: W
authors.lastname: Ashton
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wu
authors.forename: Huaibing
authors.initials: H
authors.lastname: He
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lyons
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: Ann E
authors.initials: AE
authors.lastname: Weber
mesh_terms: D000818:Animals; D001682:Biological Availability; D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats
chemical_list: D003510:Cyclohexanes; D054873:Dipeptidyl-Peptidase IV Inhibitors; D010880:Piperidines