title: 2-Cyano-4-fluoro-1-thiovalylpyrrolidine analogues as potent inhibitors of DPP-IV.
abstract: We report the synthesis and biological activity of a series of 2-cyano-4-fluoro-1-thiovalylpyrrolidine inhibitors of DPP-IV. Within this series, compound 19 provided a potent, selective, and orally active DPP-IV inhibitor which demonstrated a very long duration of action in both rat and dog.
authors.affiliation: Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA. curt.d.haffner@gsk.com
authors.forename: Curt D
authors.initials: CD
authors.lastname: Haffner
authors.forename: Darryl L
authors.initials: DL
authors.lastname: McDougald
authors.forename: Steven M
authors.initials: SM
authors.lastname: Reister
authors.forename: Brian D
authors.initials: BD
authors.lastname: Thompson
authors.forename: Christopher
authors.initials: C
authors.lastname: Conlee
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bass
authors.forename: James M
authors.initials: JM
authors.lastname: Lenhard
authors.forename: Dallas
authors.initials: D
authors.lastname: Croom
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Secosky-Chang
authors.forename: Thaddeus
authors.initials: T
authors.lastname: Tomaszek
authors.forename: Donavon
authors.initials: D
authors.lastname: McConn
authors.forename: Kevin
authors.initials: K
authors.lastname: Wells-Knecht
authors.forename: Paul R
authors.initials: PR
authors.lastname: Johnson
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D004285:Dogs; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D014633:Valine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C507188:2-cyano-4-fluoro-1-thiovalylpyrrolidine, methyl-4-methoxyphenyl; D011480:Protease Inhibitors; D011759:Pyrrolidines; D018819:Dipeptidyl Peptidase 4; D014633:Valine