Preparation of pyrrolidine and isoxazolidine benzamidines as potent inhibitors of coagulation factor Xa

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 8, 1999, Pages 1195-1200

  Fevig, John M ^a   Buriak Jr , Joseph ^a   Stouten, Pieter F W ^b   Knabb, Robert M ^a   Gilbert N, Lam ^c   Wong, Pancras C ^a   Wexler, Ruth R ^a  

^a DUPONT COMPANY   (United States)

^b PFIZER INC   (United States)

^c Department of Pharmacokinetics and Drug Metabolism   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTICOAGULANT AGENT; BLOOD CLOTTING FACTOR 10A; BLOOD CLOTTING FACTOR 10A INHIBITOR; ISOXAZOLIDINE BENZAMIDINE; PYRROLIDINE BENZAMIDINE; UNCLASSIFIED DRUG;

ANTICOAGULATION; ARTICLE; DRUG CONFORMATION; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; ENZYME INHIBITION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MOLECULAR MODEL; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

EID: 0033583470     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00164-X     Document Type: Article

References (15)

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14. 50, which is the dose needed to reduce clot weight by 50% relative to control.
15. 1/2) of less than 1h. In this model, rabbits were infused with 10 mg/kg/h of compound and blood samples were taken prior to, during and up to 4h after the infusion. Blood samples were immediately worked up by solid phase extraction and analyzed for test compound by an ex vivo anti-Xa assay or by LC/MS/MS. The high clearance observed for 25 and 30 precluded any further in vivo testing on these compounds.