title: Design of selective phenylglycine amide tissue factor/factor VIIa inhibitors.
abstract: Proof of concept experiments have shown that tissue factor/factor VIIa inhibitors have antithrombotic activity without enhancing bleeding propensity. Starting from lead compounds generated by a biased combinatorial approach, phenylglycine amide tissue factor/factor VIIa inhibitors with low nanomolar affinity and good selectivity against other serine proteases of the coagulation cascade were designed, using the guidance of X-ray structural analysis and molecular modelling.
authors.affiliation: F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland. katrin.groebke_zbinden@roche.com
authors.forename: Katrin
authors.initials: K
authors.lastname: Groebke Zbinden
authors.forename: David W
authors.initials: DW
authors.lastname: Banner
authors.forename: Jean
authors.initials: J
authors.lastname: Ackermann
authors.forename: Allan
authors.initials: A
authors.lastname: D'Arcy
authors.forename: Daniel
authors.initials: D
authors.lastname: Kirchhofer
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Ji
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Tschopp
authors.forename: Sabine
authors.initials: S
authors.lastname: Wallbaum
authors.forename: Lutz
authors.initials: L
authors.lastname: Weber
mesh_terms: D015195:Drug Design; D015942:Factor VIIa / Q000037:antagonists & inhibitors*; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis; D013329:Structure-Activity Relationship; D013925:Thromboplastin / Q000037:antagonists & inhibitors*
chemical_list: D005343:Fibrinolytic Agents; D015842:Serine Proteinase Inhibitors; C470025:phenylglycinamide; D013925:Thromboplastin; D015942:Factor VIIa; D005998:Glycine