Design, synthesis, and structure-activity relationship of a new class of amidinophenylurea-based factor VIIa inhibitors.
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.
Klingler
Otmar
O
Aventis Pharma Deutschland GmbH, Building G878, D-65926 Frankfurt, Germany. otmar.klingler@aventis.com
Matter
Hans
H
Schudok
Manfred
M
Bajaj
S Paul
SP
Czech
Joerg
J
Lorenz
Martin
M
Nestler
Hans Peter
HP
Schreuder
Herman
H
Wildgoose
Peter
P
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
D010671:Phenylurea Compounds; D015942:Factor VIIa