Discovery of a factor Xa inhibitor (3R,4R)-1-(2,2-difluoro-ethyl)-pyrrolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-[[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-amide] as a clinical candidate.
A series of (3R,4R)-pyrrolidine-3,4-dicarboxylic acid amides was investigated with respect to their factor Xa inhibitory activity, selectivity, pharmacokinetic properties, and ex vivo antithrombotic activity. The clinical candidate from this series, R1663, exhibits excellent selectivity against a panel of serine proteases and good pharmacokinetic properties in rats and monkeys. A Phase I clinical study with R1663 has been finalized.
Anselm
Lilli
L
F. Hoffmann-La Roche Ltd, Pharma Research, Basel, Switzerland.
Banner
David W
DW
Benz
Jörg
J
Zbinden
Katrin Groebke
KG
Himber
Jacques
J
Hilpert
Hans
H
Huber
Walter
W
Kuhn
Bernd
B
Mary
Jean-Luc
JL
Otteneder
Michael B
MB
Panday
Narendra
N
Ricklin
Fabienne
F
Stahl
Martin
M
Thomi
Stefan
S
Haap
Wolfgang
W
D065427:Factor Xa Inhibitors; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*
D065427:Factor Xa Inhibitors; D011759:Pyrrolidines