PYRAZINONE THROMBIN INHIBITORS

摘要

1. A compound having the formula: wherein R<1> is selected from the group consisting of halogen, preferably fluorine, C1-4alkyl, C1-4alkylthio, C1-4alkylsulfinyl and C1-4alkylsulfonyl; R<2> is selected from the group consisting of hydrogen, and lower alkyl; R<3> is selected from the group consisting of chlorine, lower alkyl, formyl and a cyano group or pharmaceutically acceptable salts thereof. 2. A compound of Claim 1, or pharmaceutically acceptable salt thereof, wherein R<2> is hydrogen. 3. A compound of Claim 1, or pharmaceutically acceptable salt thereof, selected from the group consisting of: or pharmaceutically acceptable salts thereof. 4. A compound of Claim 1, or pharmaceutically acceptable salt thereof of the formula: 5. A compound of Claim 1, or pharmaceutically acceptable salt thereof of the formula: 6. A compound of Claim 1, or pharmaceutically acceptable salt thereof of the formula: 7. A compound of Claim 1, or pharmaceutically acceptable salt thereof of the formula: 8. A compound of Claim 1, or pharmaceutically acceptable salt thereof of the formula: 9. An oral pharmaceutical composition comprising a compound of Claim 1 and a pharmaceutically acceptable carrier. 10. An intravenous pharmaceutical composition comprising a compound of Claim 1 and a pharmaceutically acceptable carrier. 11. A method for inhibiting thrombin in blood comprising adding to the blood a composition of Claim 10. 12. A method for inhibiting formation of blood platelet aggregates in blood comprising adding to the blood a composition of Claim 10. 13. A method for inhibiting thrombus formation in blood comprising adding to the blood a composition of Claim 10. 14. A method for inhibiting thrombus formation in blood comprising adding to the blood a compound of Claim 1 with a fibrinogen receptor antagonist. 15. The use of a compound of Claim 1, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for inhibiting thrombin, inhibiting thrombus formation, treating thrombus formation, or preventing thrombus formation in a mammal. 16. A method for treating or preventing venous thromboembolism and pulmonary embolism in a mammal comprising administering to the mammal a composition of Claim 10. 17. A method for treating or preventing deep vein thrombosis in a mammal comprising administering to the mammal a composition of Claim 10. 18. A method for treating or preventing cardiogenic thromboembolism in a mammal comprising administering to the mammal a composition of Claim 10. 19. A method for treating or preventing thromboembolic stroke in humans and other mammals comprising administering to the mammal a composition of Claim 10. 20. A method for treating or preventing thrombosis associated with cancer and cancer chemotherapy in a mammal comprising administering to the mammal a composition of Claim 10. 21. A method for treating or preventing unstable angina in a mammal comprising administering to the mammal a composition of Claim 10.