Design and synthesis of glycolic and mandelic acid derivatives as factor Xa inhibitors.

Abstract

A series of glycolic and mandelic acid derivatives was synthesized and investigated for their factor Xa inhibitory activity. These analogues are highly potent and selective inhibitors against fXa. In a rabbit deep vein thrombosis model, compound 26 showed significant antithrombotic effects (81% inhibition of thrombus formation) at 1.1 microM plasma concentration following intravenous administration.

• Authors: T Su, Y Wu, B Doughan, K Kane-Maguire, C K Marlowe, J P Kanter, J Woolfrey, B Huang, P Wong, U Sinha, G Park, J Malinowski, S Hollenbach, R M Scarborough, B Y Zhu
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 11 Issue 17 Pg. 2279-82 (Sep 03 2001) ISSN: 0960-894X [Print] England
• PMID: 11527714 (Publication Type: Journal Article)

Chemical References

• Acetanilides
• Amidines
• Factor Xa Inhibitors
• Mandelic Acids
• Phenylacetates
• Serine Proteinase Inhibitors
• alpha-(3-amidinylphenoxy)-2-bromo-N-(5-(pyrrolidin-1-ylcarbonyl)phenyl)phenylacetamide
• Fibrinolysin
• mandelic acid

Topics

• Acetanilides
• Amidines (chemical synthesis, chemistry, pharmacology)
• Animals
• Biological Availability
• Blood Coagulation Tests
• Drug Design
• Drug Evaluation, Preclinical (methods)
• Factor Xa Inhibitors
• Fibrinolysin (antagonists & inhibitors)
• Inhibitory Concentration 50
• Injections, Intravenous
• Mandelic Acids (chemistry)
• Phenylacetates (chemical synthesis, chemistry, pharmacology)
• Rabbits
• Rats
• Rats, Sprague-Dawley
• Serine Proteinase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Venous Thrombosis (drug therapy)