| abstract |
Cyclic oxyguanidine pyrazinone compounds are described, including compounds of the Formula (I): wherein R<3>, R<4>, R<5>, W, and A are as set forth in the specidification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. The compounds of the invention are potent inhibitors of protease, especially trypsin-like serine proteases, such as chymotripsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of trombin. Compositions for inhibiting loss of blood platelas, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation are described. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage, such as catheters, blood dialysis machines, blood collection syringes and tubes, blood lines and stents. Additionally, the compounds can be detectably labeled and employed labeled and employed fot <i>in vivo</i> imaging of thrombi. |