Nonbenzamidine acylsulfonamide tissue factor–factor VIIa inhibitors
Journal Article
·
· Bioorganic & Medicinal Chemistry Letters
Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P' binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- INDUSTRY
- OSTI ID:
- 1347765
- Journal Information:
- Bioorganic & Medicinal Chemistry Letters, Journal Name: Bioorganic & Medicinal Chemistry Letters Journal Issue: 18 Vol. 23; ISSN 0960-894X
- Country of Publication:
- United States
- Language:
- ENGLISH
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