title: Novel factor Xa inhibitors based on a benzoic acid scaffold and incorporating a neutral P1 ligand.
abstract: 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.
authors.affiliation: Aventis Pharma Deutschland GmbH, D-65926 Frankfurt, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Nazaré
authors.forename: Hans
authors.initials: H
authors.lastname: Matter
authors.forename: Otmar
authors.initials: O
authors.lastname: Klingler
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Obeidi
authors.forename: Herman
authors.initials: H
authors.lastname: Schreuder
authors.forename: Gerhard
authors.initials: G
authors.lastname: Zoller
authors.forename: Jörg
authors.initials: J
authors.lastname: Czech
authors.forename: Martin
authors.initials: M
authors.lastname: Lorenz
authors.forename: Angela
authors.initials: A
authors.lastname: Dudda
authors.forename: Anusch
authors.initials: A
authors.lastname: Peyman
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Nestler
authors.forename: Matthias
authors.initials: M
authors.lastname: Urmann
authors.forename: Armin
authors.initials: A
authors.lastname: Bauer
authors.forename: Volker
authors.initials: V
authors.lastname: Laux
authors.forename: Volkmar
authors.initials: V
authors.lastname: Wehner
authors.forename: David W
authors.initials: DW
authors.lastname: Will
mesh_terms: 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
chemical_list: D001565:Benzoates; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D008024:Ligands; D011480:Protease Inhibitors