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515511 
Journal Article 
Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3 4-(3-oxomorpholin-4-yl)phenyl -1,3-oxazolidin- 5-yl}methyl)thiophene-2-carboxamide (BAY 59-7939): An oral, direct factor Xa inhibitor 
Roehrig, S; Straub, A; Pohlmann, J; Lampe, T; Pernerstorfer, J; Schlemmer, KH; Reinemer, P; Perzborn, E 
2005 
Yes 
Journal of Medicinal Chemistry
ISSN: 0022-2623
EISSN: 1520-4804 
48 
19 
5900-5908 
English 
Despite recent progress in antithrombotic therapy, there is still an unmet medical need for safe and orally available anticoagulants. The coagulation enzyme Factor Xa (FXa) is a particularly promising target, and recent efforts in this field have focused on the identification of small-molecule inhibitors with good oral bioavailability. We identified oxazolidinone derivatives as a new class of potent FXa inhibitors. Lead optimization led to the discovery of BAY 59-7939 (5), a highly potent and selective, direct FXa inhibitor with excellent in vivo antithrombotic activity. The X-ray crystal structure of 5 in complex with human FXa clarified the binding mode and the stringent requirements for high affinity. The interaction of the neutral ligand chlorothiophene in the S1 subsite allows for the combination of good oral bioavailability and high potency for nonbasic 5. Compound 5 is currently under clinical development for the prevention and treatment of thromboembolic diseases. 
coagulation-factor xa; crystal-structures; drug design; potent; anticoagulants