title: Fluoroolefins as amide bond mimics in dipeptidyl peptidase IV inhibitors.
abstract: The synthesis, selectivity, rat pharmacokinetic profile, and drug metabolism profiles of a series of potent fluoroolefin-derived DPP-4 inhibitors (4) are reported. A radiolabeled fluoroolefin 33 was shown to possess a high propensity to form reactive metabolites, thus revealing a potential liability for this class of DPP-4 inhibitors.
authors.affiliation: Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 2000, Rahway, NJ 07065, USA. scott_edmondson@merck.com
authors.forename: Scott D
authors.initials: SD
authors.lastname: Edmondson
authors.forename: Lan
authors.initials: L
authors.lastname: Wei
authors.forename: Jinyou
authors.initials: J
authors.lastname: Xu
authors.forename: Jackie
authors.initials: J
authors.lastname: Shang
authors.forename: Shiyao
authors.initials: S
authors.lastname: Xu
authors.forename: Jianmei
authors.initials: J
authors.lastname: Pang
authors.forename: Ashok
authors.initials: A
authors.lastname: Chaudhary
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Dean
authors.forename: Huaibing
authors.initials: H
authors.lastname: He
authors.forename: Barbara
authors.initials: B
authors.lastname: Leiting
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lyons
authors.forename: Reshma A
authors.initials: RA
authors.lastname: Patel
authors.forename: Sangita B
authors.initials: SB
authors.lastname: Patel
authors.forename: Giovanna
authors.initials: G
authors.lastname: Scapin
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wu
authors.forename: Maria G
authors.initials: MG
authors.lastname: Beconi
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: Ann E
authors.initials: AE
authors.lastname: Weber
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D000577:Amides / Q000737:chemistry*; D000818:Animals; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000473:pathology; D008956:Models, Chemical; D018716:Molecular Mimicry; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000475:Alkenes; D000577:Amides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006845:Hydrocarbons, Fluorinated; D007004:Hypoglycemic Agents