title: Design, synthesis, and structure-activity relationship of a new class of amidinophenylurea-based factor VIIa inhibitors.
abstract: Selective inhibition of coagulation factor VIIa has recently gained attraction as interesting approach towards antithrombotic treatment. Using parallel synthesis supported by structure-based design and X-ray crystallography, we were able to identify a novel series of amidinophenylurea derivatives with remarkable affinity for factor VIIa. The most potent compound displays a K(i) value of 23 nM for factor VIIa.
authors.affiliation: Aventis Pharma Deutschland GmbH, Building G878, D-65926 Frankfurt, Germany. otmar.klingler@aventis.com
authors.forename: Otmar
authors.initials: O
authors.lastname: Klingler
authors.forename: Hans
authors.initials: H
authors.lastname: Matter
authors.forename: Manfred
authors.initials: M
authors.lastname: Schudok
authors.forename: S Paul
authors.initials: SP
authors.lastname: Bajaj
authors.forename: Joerg
authors.initials: J
authors.lastname: Czech
authors.forename: Martin
authors.initials: M
authors.lastname: Lorenz
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Nestler
authors.forename: Herman
authors.initials: H
authors.lastname: Schreuder
authors.forename: Peter
authors.initials: P
authors.lastname: Wildgoose
mesh_terms: D018360:Crystallography, X-Ray; D015195:Drug Design; D015942:Factor VIIa / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010671:Phenylurea Compounds; D015942:Factor VIIa