2-Cyano-4-fluoro-1-thiovalylpyrrolidine analogues as potent inhibitors of DPP-IV.
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.
Haffner
Curt D
CD
Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA. curt.d.haffner@gsk.com
McDougald
Darryl L
DL
Reister
Steven M
SM
Thompson
Brian D
BD
Conlee
Christopher
C
Fang
Jing
J
Bass
Jonathan
J
Lenhard
James M
JM
Croom
Dallas
D
Secosky-Chang
Melissa B
MB
Tomaszek
Thaddeus
T
McConn
Donavon
D
Wells-Knecht
Kevin
K
Johnson
Paul R
PR
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
C507188:2-cyano-4-fluoro-1-thiovalylpyrrolidine, methyl-4-methoxyphenyl; D011480:Protease Inhibitors; D011759:Pyrrolidines; D018819:Dipeptidyl Peptidase 4; D014633:Valine