| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1375219 | Bioorganic & Medicinal Chemistry Letters | 2006 | 5 Pages |
Highly selective and potent factor VIIa–tissue factor (fVIIa · TF) complex inhibitors were generated through structure-based design. The pharmacokinetic properties of an optimized analog (9) were characterized in several preclinical species, demonstrating pharmacokinetic characteristics suitable for once-a-day dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose-dependent manner after intravenous administration in a baboon thrombosis model, and a pharmacodynamic concentration–response model was developed to describe the platelet deposition data. Results for heparin and enoxaparin (Lovenox®) in the baboon model are also presented.
Graphical abstractHighly selective and potent factor VIIa–tissue factor (fVIIa · TF) complex inhibitors were generated through structure-based design. The pharmacokinetic properties of an optimized analog (9) were characterized in several preclinical species, demonstrating pharmacokinetic characteristics suitable for once-a-day dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose-dependent manner after intravenous administration in a baboon thrombosis model, and a pharmacodynamic concentration–response model was developed to describe the platelet deposition data. Results for heparin and enoxaparin (Lovenox®) in the baboon model are also presented.Figure optionsDownload full-size imageDownload as PowerPoint slide
