Claims
- 1. A compound of formula I
- 2. The compound of claim 1 wherein R1a is optionally substituted lower alkoxy, optionally substituted mono cyclic cycloalkyloxy, optionally substituted heterocyclylcarbonyloxy or optionally substituted mono cyclic oxaheterocyclyloxy.
- 3. The compound of claim 2 wherein R1a is optionally substituted lower alkoxy or optionally substituted mono cyclic oxaheterocyclyloxy.
- 4. The compound of claim 3 wherein R1a is methoxy, ethoxy, 2-(ethoxy)ethoxy, 2-(4-morpholinyl)ethoxy or furanyloxy.
- 5. The compound of claim 1 wherein R1b is hydrogen, optionally substituted lower alkoxy, optionally substituted mono cyclic cycloalkyloxy, optionally substituted heterocyclylcarbonyloxy or optionally substituted mono cyclic oxaheterocyclyloxy.
- 6. The compound of claim 5 wherein R1b is hydrogen or optionally substituted lower alkoxy.
- 7. The compound of claim 6 wherein R1b is methoxy or ethoxy.
- 8. The compound of claim 1 wherein R1a and R1b are lower alkoxy.
- 9. The compound of claim 8 wherein R1a and R1b are methoxy or ethoxy.
- 10. The compound of claim 1 wherein R1c is hydrogen or optionally substituted lower alkoxy.
- 11. The compound of claim 10 wherein R1c is hydrogen, methoxy or ethoxy.
- 12. The compound of claim 1 wherein R2 is
- 13. The compound of claim 1 wherein R2 is
- 14. The compound of claim 1 wherein R3 is hydrogen, ortho or para s fluoro, or meta methyl, trifluoromethyl, methoxy, fluoro, chloro, bromo or carbamoyl.
- 15. The compound of claim 1 wherein R4 is hydrogen or methyl.
- 16. The compound of claim 1 wherein Za is N.
- 17. The compound of claim 1 wherein Za is CH.
- 18. The compound of claim 1 wherein Zb is NH.
- 19. The compound of claim 1 wherein Zb is O.
- 20. A compound of claim 1 which is selected from the following species:
2-anilino-6-quinoxalinol; 2-((R)-α-Methylbenzyl-amino)-6,7-diethoxyquinoxaline; 2-anilino-6-isopropoxyquinoxaline; 2-Phenoxy-6-methoxyquinoxaline; (3-Bromobenzyl)-(6,7-dimethoxyquinoxalin-2-yl)-amine; 2-(3-Carbamoylphenylamino)-6-methoxyquinoxaline; 2-(2-Fluorophenylamino)-6,7-diethoxyquinoxaline; 2-(3-Trifluoromethylphenylamino)-6,7-diethoxyquinoxaline; Phenyl-[6-(tetrahydrofuran-3(R)-yloxy)quinoxalin-2-yl]amine; Benzyl-(6,7-diimethoxyquinoxalin-2-yl)-amine; 2-((S)-α-Methylbenzyl-amino)-6,7-diethoxyquinoxaline; 2-Benzylamino-6,7-diethoxyquinoxaline; (6-Methoxyquinoxalin-2-yl)-(3-methylphenyl)-amine; 6-Methoxy-2-phenylamilno-quinoxaline; 2-Anilino-6-ethoxyquinoxaline; 2-(3-Methoxyphenylamino)-6,7-diethoxyquinoxaline; 2-(4-Fluorophenylamino)-6,7-diethoxyquinoxaline; 6,7-Diethoxy-2-phenoxyquinoxaline; 2-Phenylamino-6,7-diethoxyquinoxaline; (6,7-Dimethoxyquinoxalin-2-yl)-(3-fluorophenyl)-amine; 2-(3-Fluorophenylamino)-6,7-diethoxyquinoxaline; (3-Bromophenyl)-(6,7-dimethoxyquinoxalin-2-yl)-amine; (6,7-Dimethoxyquinoxalin-2-yl)-phenyl-amine; and (3-Chlorophenyl)-(6,7-dimethoxyquinoxalin-2-yl)-amine, or an N-oxide thereof, hydrate thereof, solvate thereof, prodnig thereof, or pharmaceutically acceptable salt thereof.
- 21. A compound of claim 1 which is selected from the species:
Phenyl-[6-(tetrahydrofuran-3 (R)-yloxy)quinoxalin-2-yl]amine; Benzyl-(6,7-dimethoxyquinoxalin-2-yl)-amine; 2-((S)-α-Methylbenzyl-amino)-6,7-diethoxyquinoxaline; 2-Benzylamino)-6,7-diethoxyquinoxaline; (6-Methoxyquinoxalin-2-yl)-(3-methylphenyl)-amine; 6-Methoxy-2-phenylamino-quinoxaline; 2-Anilino-6-ethoxyquinoxaline; 2-(3-Methoxyphenylamino)-6,7-diethoxyquinoxaline; 2-(4-Fluorophenylamiio)-6,7-diethoxyquinoxaline; 6,7-Diethoxy-2-phenoxyquinoxaline; 2-Phenylamino-6,7-diethoxyquinoxaline; (6,7-Dimethoxyquinoxalin-2-yl)-(3-fluorophenyl)-amine; 2-(3-Fluorophenylamino)-6,7-diethoxyquinoxaline; (3-Bromophenyl)-(6,7-dimethoxyquinoxal in-2-yl)-amine; (6,7-Dimethoxyquinoxalin-2-yl)-phenyl-amine; and (3-Chlorophenyl)-(6,7-dimethoxyquinoxalin-2-yl)-amine, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 22. The compound according to claim 1 which is Phenyl-[6-(tetrahydrofuran-3(R)-yloxy)quinoxalin-2-yl]amine, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 23. The compound according to claim 1 which is Benzyl-(6,7-dimethoxyquinoxalin-2-yl)-amine, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 24. The compound according to claim 1 which is 2-((S)-(α-Methylbenzyl-amino)-6,7-diethoxyquinoxaline, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 25. The compound according to claim 1 which is 2-Benzylamino-6,7-diethoxyquinoxaline, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 26. The compound according to claim 1 which is (6-Methoxyquinoxalin-2-yl)-(3-methylphenyl)-amine, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 27. The compound according to claim 1 which is 6-Methoxy-2-phenylamino-quinoxaline, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 28. The compound according to claim 1 which is 2-Anilino-6-ethoxyquinoxaline, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 29. The compound according to claim 1 which is 2-(3-Methoxyphenylamino)-6,7-diethoxyquinoxaline, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 30. The compound according to claim 1 which is 2-(4-Fluorophenylamino)-(6,7-diethoxyquiuoxaline, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 31. The compound according to claim 1 which is 6,7-Diethoxy-2-phenoxyquinoxaline, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 32. The compound according to claim 1 which is 2-Phenylamino-6,7-dietlioxyquinoxaline, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 33. The compound according to claim 1 which is (6,7-Dimethoxyquinoxalin-2-yl)-(3-fluorophenyl)-amine, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 34. The compound according to claim 1 which is 2-(3-Fluorophenylamino)-6,7-diethoxyquinoxaline, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 35. The compound according to claim 1 which is (3-Bromophenyl)-(6,7-dimethoxyquinoxalin-2-yl)-amine, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 36. The compound according to claim 1 which is (6,7-Dimethoxyquinoxalin-2-yl)-phenyl-amine, or an N-oxide thereof, hydrate thereof solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 37. The compound according to claim 1 which is (3-Chlorophenyl)-(6,7-dimethoxyquinoxalin-2yl)-amine, or an N-oxide thereof, hydrate thereof, solvate thereof, prodrug thereof, or pharmaceutically acceptable salt thereof.
- 38. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
- 39. A method of inhibiting PDGF tyrosine kinase activity comprising contacting a compound according to claim 1 to a composition containing a PDGF tyrosine kinase.
- 40. A method of inhibiting Lck tyrosile kinase activity comprising contacting a compound according to claim 1 to a composition containing a Lck tyrosine kinase.
- 41. A method of inhibiting cell proliferation, differentiation, or mediator release in a patient suffering from a disorder characterized by such proliferation and/or differentiation and/or mediator release comprising administering to said patient a pharmaceutically effective amount of the compound according to claim 1, or a pharmaceutically acceptable salt thereof.
- 42. A method for treating a patient subject to a pathology linked to a hyperproliferative disorder, said method comprising administrating to said patient a pharmaceutically effective amount of the compound according to claim 1, or a pharmaceutically acceptable salt thereof.
- 43. The method according to claim 42, wherein said pathology is restenosis.
- 44. A method of treating restenosis in a patient comprising administering to said patient in need of such treatment a pharmaceutically effective amount of the compound according to claim 1 at a predetermined site.
- 45. The method according to claim 42, wherein said hyperproliferative disorder is at a site of mechanical injury to an arterial wall produced by treatment of an atherosclerotic lesion by angioplasty.
- 46. The method according to claim 44, wherein the compound according to claim 1 is administered by means of an angioplasty balloon coated with a hydrophilic film saturated with the compound according to claim 1.
- 47. The method according to claim 44, wherein the compound according to claim 1 is administered by means of a catheter comprising an infusion chamber containing a solution of the compound according to claim 1.
- 48. The method according to claim 44 wherein the compound according to claim 1 is administered by means of a coating on a stent device, wherein the coating comprises a compound according to claim 1.
- 49. The method according to claim 42 wherein the pathology linked to a hyperproliferative disorder is a cancer susceptible to treatment by inhibition of PDGF tryosine kinase.
- 50. The method according to claim 49 wherein the cancer is brain cancer, ovarian cancer, colon cancer, prostate cancer, lung cancer, Kaposi's sarcomo or malignant melanoma.
- 51. A method for treating inflammation in a patient suffering from such comprising administering to said patient an effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation-in-part of International Patent Application No. PCT/US98/10999, filed May 28, 1998, which in turn is a continuation-in-part of U.S. Ser. No. 08/972,614, filed Nov. 18, 1997, which in turn is a continuation-in-part of U.S. Ser. No. 08/864,455, filed May 18, 1997, now abandoned.
Divisions (2)
|
Number |
Date |
Country |
Parent |
09675741 |
Sep 2000 |
US |
Child |
10357240 |
Feb 2003 |
US |
Parent |
09198716 |
Nov 1998 |
US |
Child |
09675741 |
Sep 2000 |
US |
Continuation in Parts (3)
|
Number |
Date |
Country |
Parent |
PCT/US98/10999 |
May 1998 |
US |
Child |
09198716 |
Nov 1998 |
US |
Parent |
08972614 |
Nov 1997 |
US |
Child |
PCT/US98/10999 |
May 1998 |
US |
Parent |
08864455 |
May 1997 |
US |
Child |
08972614 |
Nov 1997 |
US |