title: Structure-based design of amidinophenylurea-derivatives for factor VIIa inhibition.
abstract: The amidinophenylurea scaffold was earlier shown to provide an excellent template for the synthesis of novel and potent inhibitors of the blood coagulation factor VIIa. In this contribution we describe the structure-based design of potent ligands guided by X-ray crystallography, molecular modeling and docking studies. The design and synthetic efforts were directed towards novel modifications to explore the protease binding region close to the S4 subsite.
authors.affiliation: Aventis Pharma Deutschland GmbH, Building G878, D-65926 Frankfurt, Germany. otmar.klinger@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: Monica
authors.initials: M
authors.lastname: Donghi
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: Hauke
authors.initials: H
authors.lastname: Szillat
authors.forename: Herman
authors.initials: H
authors.lastname: Schreuder
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D015942:Factor VIIa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D010447:Peptide Hydrolases / Q000378:metabolism; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D005343:Fibrinolytic Agents; D010671:Phenylurea Compounds; D010447:Peptide Hydrolases; D015942:Factor VIIa