The rabbits are euthanized and the thrombus excised by surgical dissection and characterized by weight and histology.The compounds of the present invention may be synthesized by either solid or liquid phase methods described and referenced in standard textbooks, or by a combination of both methods.Abstract: Discoveries that lead to ZK 807834 (CI-1031, 2a), a potent and selective factor Xa (fXa) inhibitor currently in clinical testing as an intravenous.Starting materials used in any of these methods are commercially available from chemical vendors such as Aldrich, Sigma, Nova Biochemicals, Bachem Biosciences, and the like, or may be readily synthesized by known procedures.
The products may be further purified by column chromatography or other appropriate methods.Accordingly, a method for preventing or treating a condition in a mammal characterized by undesired thrombosis comprises administering to the mammal a therapeutically effective amount of a compound of this invention.Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed.A standard curve of thrombin generation by an equivalent amount of untreated complex is then used for determination of percent inhibition.
Polymers and semipermeable polymer matrices may be formed into shaped articles, such as valves, stents, tubing, prostheses and the like.Aryl groups preferably have 6-14 carbon atoms making up the ring(s) structure, while heteroaryls preferably have 1-4 heteroatoms, with the remaining 4-10 atoms being carbon atoms.Selective inhibition of factor xa during thrombolytic therapy markedly improves coronary artery patency in a canine model of coronary thrombosis Academic Article.Polypeptides derived from hematophagous organisms have been reported which are highly potent and specific inhibitors of factor Xa. U.S. Pat. No. 4,588,587 awarded to Gasic, describes anticoagulant activity in the saliva of the Mexican leech, Haementeria officinalis.Selective factor Xa inhibition improves efficacy of venous thromboembolism prophylaxis in orthopedic surgery.Factor Xa is a key enzyme in the production of thrombin from its precursor prothrombin and is an important target for antithrombotic drug development.Learn vocabulary, terms, and more with flashcards, games, and other study tools.
The compounds and compositions are useful in vitro or in vivo for preventing or treating conditions in mammals characterized by undesired thrombosis.Plasma contains an endogenous inhibitor of both the factor VIIa-tissue factor (TF) complex and factor Xa called tissue factor pathway inhibitor (TFPI).
The blood coagulation cascade involves the conversion of a variety of inactive enzymes (zymogens) into active enzymes which ultimately convert the soluble plasma protein fibrinogen into an insoluble matrix of highly cross-linked fibrin.Such polymers can include polyvinylpyrrolidinone, pyran copolymer, polyhydroxy-propyl-methacrylamide-phenol, polyhydroxyethyl-aspartamide-phenol, or polyethyleneoxide-polylysine substituted with palmitoyl residues.
Accordingly, the compounds may exist as diastereoisomer, enantiomers or mixtures thereof.The amount of active ingredient in these compositions is such that a suitable dosage in the range indicated is obtained.
The chemistry of using the various R 4 and R 5 substituents (H, —OH, C 1-6 alkyl and C 1-4 alkylaryl) is also well known in the art.A preferred embodiment of compounds of general formula III have the following stereochemistry.
Trials compared rivaroxaban (10 mg once daily) with enoxaparin for thromboprophylaxis after hip or knee arthroplasty.The reaction products are isolated and purified by conventional methods, typically by solvent extraction into a compatible solvent.
Particularly preferred are the ammonium, potassium, sodium, calcium and magnesium salts.Although platelets and blood coagulation are both involved in thrombus formation, certain components of the coagulation cascade are primarily responsible for the amplification or acceleration of the processes involved in platelet aggregation and fibrin deposition.Mechanism of action An oral, direct and highly selective Factor Xa inhibitor.The antithrombotic efficacy of the compounds of this invention can readily be evaluated using a series of studies in rabbits, as described below.For example, the free acid or free base form of a compound of one of the formulas above can be reacted with one or more molar equivalents of the desired acid or base in a solvent or solvent mixture in which the salt is insoluble, or in a solvent like water after which the solvent is removed by evaporation, distillation or freeze drying.