Low molecular weight activated protein C inhibitors as a potential treatment for hemophilic disorders.

Abstract

The synthesis and evaluation of inhibitors of activated protein C (aPC) are reported. This serine protease is partly responsible for the degradation of factor VIIIa, involved in the regulation of bleeding in hemophilia A. Benzamidine-containing derivatives were found to be potent aPC inhibitors, some of them showing selectivity against the procoagulant protease thrombin. Moreover, compound 1 significantly restored the generation of thrombin in hemophiliac plasma.

• Authors: Guillaume De Nanteuil, Philippe Gloanec, Suzette Béguin, Peter L A Giesen, H Coenraad Hemker, Philippe Mennecier, Alain Rupin, Tony J Verbeuren
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 49 Issue 17 Pg. 5047-50 (Aug 24 2006) ISSN: 0022-2623 [Print] United States
• PMID: 16913694 (Publication Type: Journal Article)

Chemical References

• Benzamidines
• Protein C
• Serine Proteinase Inhibitors
• Factor VIIIa
• Thrombin

Topics

• Benzamidines (chemistry, pharmacology)
• Factor VIIIa (metabolism)
• Hemophilia A (drug therapy)
• Hemorrhage (prevention & control)
• Humans
• Molecular Structure
• Molecular Weight
• Protein C (antagonists & inhibitors)
• Serine Proteinase Inhibitors (chemistry, pharmacology)
• Structure-Activity Relationship
• Thrombin (antagonists & inhibitors, biosynthesis)