Design of novel aminopyrrolidine factor Xa inhibitors from a screening hit.
Starting from a hit identified by focused screening, 3-aminopyrrolidine factor Xa inhibitors were designed. The binding mode as determined by X-ray structural analysis as well as the pharmacokinetic behaviour of selected compounds is discussed.
Zbinden
Katrin Groebke
KG
F Hoffmann - La Roche Ltd, Basel, Switzerland. katrin.groebke_zbinden@roche.com
Anselm
Lilli
L
Banner
David W
DW
Benz
Jörg
J
Blasco
Francesca
F
Décoret
Guillaume
G
Himber
Jacques
J
Kuhn
Bernd
B
Panday
Narendra
N
Ricklin
Fabienne
F
Risch
Philippe
P
Schlatter
Daniel
D
Stahl
Martin
M
Thomi
Stefan
S
Unger
Robert
R
Haap
Wolfgang
W
D000634:Aminoquinolines / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000990:Antithrombin III / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015951:Factor Xa / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation
D000634:Aminoquinolines; D000990:Antithrombin III; D015951:Factor Xa