Claims for Patent: 6,280,959

Summary for Patent: 6,280,959

Title:	Metal complexes
Abstract:	The invention describes zinc chelated dimeric cell-surface receptor ligands, pharmaceutical compositions containing these compounds, methods of using these compounds as agonist of dimeric cell-surface receptors. Novel processes used in preparing the compounds are also described. Further, the invention describes novel receptor binding moieties of the zinc chelated cell-surface receptor ligands.
Inventor(s):	Gleason; John G. (Downingtown, PA), Luengo; Juan I. (Audubon, PA)
Assignee:	SmithKline Beecham Corporation (Philadelphia, PA)
Application Number:	09/530,307
Patent Claims:	1. A method for agonizing dimeric cell-surface receptors in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a zinc chelated dimeric cell-surface receptor ligand. 2. A method for agonizing dimeric cell-surface receptors in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of an organic molecule having a molecular weight from about 100 to about 850, containing of from 1 to 4 zinc binding motifs and provided that each zinc binding motif forms at least two coordinate bonds to a zinc ion. 3. A method for identifying agonists of dimeric cell-surface receptors which comprises contacting the receptor with dimeric cell-surface receptor ligand candidates in the presence of a zinc ion source, and selecting ligand candidates which bind to the receptor. 4. A process for the preparation of a zinc chelated dimeric cell-surface receptor ligand which comprises reacting one or more receptor binding moieties and a zinc ion source followed by optional isolation of the zinc chelated dimeric cell-surface receptor ligand. 5. A zinc chelated cell-surface receptor ligand prepared by the process of claim 4. 6. A zinc chelated cell-surface receptor ligand. 7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 5. 8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 6. 9. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and an effective amount of a compound of claim 5 which process comprises bringing the compound into association with the pharmaceutically acceptable carrier or diluent. 10. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and an effective amount of a compound of claim 6 which process comprises bringing the compound into association with the pharmaceutically acceptable carrier or diluent. 11. An isolated dimeric cell-surface receptor binding moiety of a zinc chelated cell-surface receptor ligand. 12. A dimeric cell-surface receptor binding moiety. 13. The method of claim 1 wherein the cell-surface receptor is the EPO receptor. 14. The method of claim 2 wherein the cell-surface receptor is the EPO receptor. 15. A method for agonizing the EPO receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 11. 16. A method for agonizing the EPO receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 12. 17. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 11. 18. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 12. 19. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and an effective amount of a compound of claim 11 which process comprises bringing the compound into association with the pharmaceutically acceptable carrier or diluent. 20. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and an effective amount of a compound of a compound of claim 12 which process comprises bringing the compound into association with the pharmaceutically acceptable carrier or diluent. 21. A method for agonizing dimeric cell-surface receptors in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 11. 22. A method for agonizing dimeric cell-surface receptors in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 12. 23. A compound of claim 11 for use as an active therapeutic substance. 24. A compound of claim 12 for use as an active therapeutic substance. 25. The method of claim 1 wherein the dimeric cell-surface receptor is the M-CSF receptor. 26. The method of claim 2 wherein the dimeric cell-surface receptor is the M-CSF receptor. 27. A method for agonizing the M-CSF receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 11. 28. A method for agonizing the M-CSF receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 12. 29. The method of claim 1 wherein the dimeric cell-surface receptor is the GRH receptor. 30. The method of claim 2 wherein the dimeric cell-surface receptor is the GRH receptor. 31. A method for agonizing the GRH receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 11. 32. A method for agonizing the GRH receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 12. 33. The method of claim 1 wherein the dimeric cell-surface receptor is the TPO receptor. 34. The method of claim 2 wherein the dimeric cell-surface receptor is the TPO receptor. 35. A method for agonizing the TPO receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 11. 36. A method for agonizing the TPO receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 12. 37. The method of claim 1 wherein the dimeric cell-surface receptor is the leptin receptor. 38. The method of claim 2 wherein the dimeric cell-surface receptor is the leptin receptor. 39. A method for agonizing the leptin receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 11. 40. A method for agonizing the leptin receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 12. 41. The method of claim 1 wherein the dimeric cell-surface receptor is the IFN receptor. 42. The method of claim 2 wherein the dimeric cell-surface receptor is the IFN receptor. 43. A method for agonizing the IFN receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 11. 44. A method for agonizing the IFN receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 12. 45. The method of claim 1 wherein the dimeric cell-surface receptor is the insulin receptor. 46. The method of claim 2 wherein the dimeric cell-surface receptor is the insulin receptor. 47. A method for agonizing the insulin receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 11. 48. A method for agonizing the insulin receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 12. 49. The method of claim 1 wherein the dimeric cell-surface receptor is selected from the TRK receptors. 50. The method of claim 2 wherein the dimeric cell-surface receptor is selected from the TRK receptors. 51. A method for agonizing a selected TRK receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 11. 52. A method for agonizing a selected TRK receptor in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of claim 12. 53. The method of claim 1 wherein said metal chelated dimeric cell-surface receptor ligand comprises a symmetrical multimer of a receptor binding moiety.