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
Susanne Roehrig, Alexander Straub, Jens Pohlmann, Thomas Lampe, Josef Pernerstorfer, Karl-Heinz Schlemmer, Peter Reinemer, Elisabeth Perzborn
Abstract
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.
Pharmacology, Toxicology and Pharmaceutical Science
14
8%
Biochemistry, Genetics and Molecular Biology
11
6%
Other
17
10%
Unknown
38
22%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 34. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 February 2022.
All research outputs
#1,269,537
of 26,562,579 outputs
Outputs from Journal of Medicinal Chemistry
#302
of 23,623 outputs
Outputs of similar age
#1,657
of 70,052 outputs
Outputs of similar age from Journal of Medicinal Chemistry
#2
of 138 outputs
Altmetric has tracked 26,562,579 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 23,623 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has done particularly well, scoring higher than 98% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 70,052 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 138 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 98% of its contemporaries.
