Potent non-nitrile dipeptidic dipeptidyl peptidase IV inhibitors.
The synthesis and structure-activity relationships of novel dipeptidyl peptidase IV inhibitors replacing the classical cyanopyrrolidine P1 group with other small nitrogen heterocycles are described. A unique potency enhancement was achieved with beta-branched natural and unnatural amino acids, particularly adamantylglycines, linked to a (2S,3R)-2,3-methanopyrrolidine based scaffold.
Simpkins
Ligaya M
LM
Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08543-5400, USA.
Bolton
Scott
S
Pi
Zulan
Z
Sutton
James C
JC
Kwon
Chet
C
Zhao
Guohua
G
Magnin
David R
DR
Augeri
David J
DJ
Gungor
Timur
T
Rotella
David P
DP
Sun
Zhong
Z
Liu
Yajun
Y
Slusarchyk
William S
WS
Marcinkeviciene
Jovita
J
Robertson
James G
JG
Wang
Aiying
A
Robl
Jeffrey A
JA
Atwal
Karnail S
KS
Zahler
Robert L
RL
Parker
Rex A
RA
Kirby
Mark S
MS
Hamann
Lawrence G
LG
D004151:Dipeptides / Q000737:chemistry* / Q000494:pharmacology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009570:Nitriles / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles