title: 4-Amino cyclohexylglycine analogues as potent dipeptidyl peptidase IV inhibitors.
abstract: Substituted 4-amino cyclohexylglycine analogues were evaluated for DP-IV inhibitory properties. Bis-sulfonamide 15e was an extremely potent 2.6 nM inhibitor of the enzyme with excellent selectivity over all counterscreens. 2,4-difluorobenzenesulfonamide 15b and 1-naphthyl amide 16b, however, combined an acceptable in vitro profile with good pharmacokinetic properties in the rat, and 15b was orally efficacious at 3 mpk in an OGTT in lean mice.
authors.affiliation: Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 2000, Rahway, NJ 07065, USA. emma_parmee@merck.com
authors.forename: Emma R
authors.initials: ER
authors.lastname: Parmee
authors.forename: Jiafang
authors.initials: J
authors.lastname: He
authors.forename: Anthony
authors.initials: A
authors.lastname: Mastracchio
authors.forename: Scott D
authors.initials: SD
authors.lastname: Edmondson
authors.forename: Larry
authors.initials: L
authors.lastname: Colwell
authors.forename: George
authors.initials: G
authors.lastname: Eiermann
authors.forename: William P
authors.initials: WP
authors.lastname: Feeney
authors.forename: Bahanu
authors.initials: B
authors.lastname: Habulihaz
authors.forename: Huaibing
authors.initials: H
authors.lastname: He
authors.forename: Ruth
authors.initials: R
authors.lastname: Kilburn
authors.forename: Barbara
authors.initials: B
authors.lastname: Leiting
authors.forename: Kathryn
authors.initials: K
authors.lastname: Lyons
authors.forename: Frank
authors.initials: F
authors.lastname: Marsilio
authors.forename: Reshma A
authors.initials: RA
authors.lastname: Patel
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Petrov
authors.forename: Jerry
authors.initials: J
authors.lastname: Di Salvo
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wu
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: Ann E
authors.initials: AE
authors.lastname: Weber
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D051638:Ether-A-Go-Go Potassium Channels; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice; D015221:Potassium Channels / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011480:Protease Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats
chemical_list: D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; D007004:Hypoglycemic Agents; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011480:Protease Inhibitors; D018819:Dipeptidyl Peptidase 4; D005998:Glycine