Patent EA-003254-B1 (EA)
Title: Vitronectin receptor antagonist
Inventor: MILLER WILLIAM H
IPC: A61K33/243
Filed: 1999-12-03
Abstract: 1.A compound according to formula (I): or a pharmaceutically acceptable salt thereof. 2. A pharmaceutical composition which comprises a compound according to claim 1 and a pharmaceutically acceptable carrier. 3. A pharmaceutical composition which comprises a compound according to claim 1, an antineoplastic agent and a pharmaceutically acceptable carrier. 4. The pharmaceutical composition according to claim 3 wherein the antineoplastic agent is topotecan. 5. The pharmaceutical composition according to claim 3 wherein the antineoplastic agent is cisplatin. 6. A method of treating a disease state in which antagonism of the alphavbeta3 receptor is indicated which comprises administering to a subject in need thereof a compound according to claim 1. 7. A method of treating a disease state in which antagonism of the alphavbeta5 receptor is indicated which comprises administering to a subject in need thereof a compound according to claim 1. 8. A method of treating osteoporosis which comprises administering to a subject in need thereof a compound according to claim 1. 9. A method for inhibiting angiogenesis which comprises administering to a subject in need thereof a compound according to claim 1. 10. A method for inhibiting tumor growth or tumor metastasis which comprises administering to a subject in need thereof a compound according to claim 1. 11. A method of treating atherosclerosis or restenosis which comprises administering to a subject in need thereof a compound according to claim 1. 12. A method of treating inflammation which comprises administering to a subject in need thereof a compound according to claim 1. 13. A method of inhibiting tumor growth which comprises administering stepwise or in physical combination a compound according to claim 1 and an antineoplastic agent. 14. The method according to claim 13 wherein the antineoplastic agent is topotecan. 15. The method according to claim 13 wherein the antineoplastic agent is cisplatin. 16. A compound according to formula (II): or a pharmaceutically acceptable salt thereof. 17. A process for preparing a compound of the formula (I) as defined in claim 1, which process comprises reacting a compound of formula (III): with 2- (5,6,7,8-tetrahydro-1, 8-naphthyridin-2-yl)-1-ethanol in a reaction mediated by the complex formed between diisopropyl azodicarboxylate and triphenylphosphine, followed by ester hydolysis using aqueous base. 18. The use of a compound of the formula (I) as defined in claim 1 in the manufacture of a medicament for the treatment of diseases in which antagonism of the alphavbeta3 receptor is indicated. 19. The use of a compound of the formula (I) as defined in claim 1 in the manufacture of a medicament for the treatment of diseases in which antagonism of the alphavbeta5 receptor is indicated. 20. The use of a compound of the formula (I) as defined in claim 1 in the manufacture of a medicament for the treatment of osteoporosis. 21. The use of a compound of the formula (I) as defined in claim 1 in the manufacture of a medicament for the inhibition of angiogenesis. 22. The use of a compound of the formula (I) as defined in claim 1 in the manufacture of a medicament for the inhibition of tumor growth or tumor metastasis. 23. The use of a compound of the formula (I) as defined in claim 1 in the manufacture of a medicament for the treatment of atherosclerosis or restenosis. 24. The use of a compound of the formula (I) as defined in claim 1 in the manufacture of a medicament for the treatment of inflammation. 25. The use of a compound of the formula (I) as defined in claim 1 and an antineoplastic agent in the manufacture of a medicament for the inhibition of tumor growth in physical combination or for stepwise administration. 26. The use according to claim 25 wherein the antineoplastic agent is topotecan. 27. The use according to claim 25 wherein the antineoplastic agent is cisplatin. 28. The use of a compound of the formula (I) as defined in claim 1 and an inhibitor of bone resorption in the manufacture of a medicament for the treatment of osteoporosis in physical combination or for stepwise administration.