Novel factor Xa inhibitors based on a benzoic acid scaffold and incorporating a neutral P1 ligand.
A series of novel, highly potent, achiral factor Xa inhibitors based on a benzoic acid scaffold and containing a chlorophenethyl moiety directed towards the protease S1 pocket is described. A number of structural features, such as the requirements of the P1, P4 and ester-binding pocket ligands were explored with respect to inhibition of factor Xa. Compound 46 was found to be the most potent compound in a series of antithrombotic secondary assays.
Nazaré
Marc
M
Aventis Pharma Deutschland GmbH, D-65926 Frankfurt, Germany.
Matter
Hans
H
Klingler
Otmar
O
Al-Obeidi
Fahad
F
Schreuder
Herman
H
Zoller
Gerhard
G
Czech
Jörg
J
Lorenz
Martin
M
Dudda
Angela
A
Peyman
Anusch
A
Nestler
Hans Peter
HP
Urmann
Matthias
M
Bauer
Armin
A
Laux
Volker
V
Wehner
Volkmar
V
Will
David W
DW
D001565:Benzoates / Q000138:chemical synthesis / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D004355:Drug Stability; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding; D013329:Structure-Activity Relationship
D001565:Benzoates; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D008024:Ligands; D011480:Protease Inhibitors