Claims
- 1. A process for the preparation of a compound of the formula
- 2. The process of claim 1, wherein R5 is hydrogen.
- 3. The process of claim 1, wherein R2 is amino or n-propionylamino.
- 4. The process of claim 1, wherein R2 is C1-C3 alkyl.
- 5. The process of claim 4, wherein R2 is methyl.
- 6. The process of claim 1, wherein Z is substituted or unsubstituted heteroaryl.
- 7. The process of claim 6, wherein Z is selected from the group consisting of substituted and unsubstituted indolyl, furyl, thienyl, pyridyl, benzofuryl, benzothienyl, imidazolyl, pyrazolyl, thiazolyl, benzothiazolyl, quinolinyl, and 4-(2-benzyloxazolyl).
- 8. The process of claim 1, wherein Z is selected from the group consisting of unsubstituted phenyl, mono-, di- and trisubstituted phenyl.
- 9. The process of claim 8, wherein Z is phenyl substituted with one or more of amino, halogen, hydroxyl, nitro, C1-C6 alkyl, C1-C6 alkoxy, carboxy, C1-C6 trihaloalkyl and cyano.
- 10. The process of claim 1, wherein R1 is C1-C6 alkyl.
- 11. The process of claim 10, wherein R1 is methyl.
- 12. The process of claim 1, wherein R1 is methyl, R2 is amino or n-propionylamino, R5 is hydrogen and Z is phenyl.
- 13. The process of claim 1, wherein R1 is trihalomethyl or C1-C6 alkyl, and the compound of the formula IV is prepared by a process comprising:
(a) deprotonating a compound of the formula 67 with a strong base, and treating the resulting enolate with a chlorophosphate reagent; (b) treating the product of step (a) with a strong base and an alkylating agent of the formula (VI) R1-Q (VI) wherein Q is a leaving group.
- 14. The process of claim 13, wherein R1 is C1-C6 alkyl.
- 15. The process of claim 13, wherein Y is 4-sulfamylphenyl or 4-propionylamino-phenylsulfonyl.
- 16. The process of claim 1, wherein R1 is a group of the formula II, and the alkyne of the formula IV is prepared by a process comprising:
(a) adding bromine to an alkene of the formula Xb 68(b) treating the product of step (b) with a base at a temperature of about 60 to about 100° C.
- 17. The process of claim 16, wherein the base used in step (ii) is an alkali metal hydroxide.
- 18. The process of claim 16, wherein Y is 4-sulfamylphenyl.
- 19. The process of claim 1, wherein R1 is trifluoromethyl and the alkyne of the formula III is prepared by a process comprising: deprotonating an acetylene of the formula VII
- 20. The process of claim 19, wherein the trifluoromethyl alkylating agent is S-(trifluoromethyl)phenyl-4-fluorophenyl-3-nitrophenylsulfonium triflate.
- 21. A process for the preparation of a compound of the formula Ib′
- 22. The process of claim 21, wherein R1 is methyl, R5 is hydrogen, R6 is ethyl, Z is phenyl and M is sodium.
- 23. A compound of the formula IX
- 24. The compound of claim 23, wherein R5 is H.
- 25. The compound of claim 23, wherein R1 is C1-C6 alkyl.
- 26. The compound of claim 25, wherein R1 is methyl.
- 27. The compound of claim 23, wherein R2 is amino.
- 28. The compound of claim 23, wherein Z is substituted or unsubstituted heteroaryl.
- 29. The compound of claim 28, wherein Z is selected from the group consisting of substituted and unsubstituted indolyl, furyl, thienyl, pyridyl, benzofuryl, benzothienyl, imidazolyl, pyrazolyl, thiazolyl, benzothiazolyl, quinolinyl, and 4-(2-benzyloxazolyl).
- 30. The compound of claim 23, wherein Z is selected from the group consisting of unsubstituted phenyl, mono-, di-, and trisubstituted phenyl.
- 31. The compound of claim 30, wherein Z is phenyl substituted with one or more of amino, halogen, hydroxyl, nitro, C1-C6 alkyl, C1-C6 alkoxy, carboxy, C1-C6 trihaloalkyl and cyano.
- 32. The compound of claim 23 wherein R1 is methyl, R2 is amino, R5 is H and Z is phenyl.
- 33. The compound of claim 23, wherein R2 is C1-C6 alkanoylamino.
- 34. The compound of claim 33, wherein R2 is n-propionylamino.
- 35. The compound of claim 33, wherein R1 is methyl, R5 is H and Z is phenyl.
- 36. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 23, or a pharmaceutically acceptable salt thereof.
- 37. A method for treating a cyclooxygenase-mediated disorder comprising administering to a patient in need of such treatment an effective amount of a compound according to claim 23, or a pharmaceutically acceptable salt thereof.
- 38. A method for treating inflammation or an inflammation-mediated disorder comprising administering to a subject in need of such treatment an effective amount of a compound according to claim 23, or a pharmaceutically acceptable salt thereof.
- 39. A method for treating neoplasia comprising administering to a patient in need of such treatment an effective amount of a compound according to claim 23, or a pharmaceutically acceptable salt thereof.
- 40. A method for treating an angiogenesis-mediated disorder comprising administering to a patient in need of such treatment an effective amount of a compound according to claim 25, or a pharmaceutically acceptable salt thereof.
- 41. A process for the preparation of a compound of the formula IX
- 42. The process of claim 41, wherein R5 is H.
- 43. The process of claim 41, wherein R1 is C1-C6 alkyl.
- 44. The process of claim 43, wherein R1 is methyl.
- 45. The process of claim 41, wherein R2 is amino or n-propionylamino.
- 46. The process of claim 41, wherein Z is substituted or unsubstituted heteroaryl.
- 47. The process of claim 46, wherein Z is selected from the group consisting of substituted and unsubstituted indolyl, furyl, thienyl, pyridyl, benzofuryl, benzothienyl, imidazolyl, pyrazolyl, thiazolyl, benzothiazolyl, quinolinyl, and 4-(2-benzyloxazolyl).
- 48. The process of claim 41, wherein Z is selected from the group consisting of unsubstituted phenyl, mono-, di-, and trisubstituted phenyl.
- 49. The process of claim 48, wherein Z is phenyl substituted with one or more of amino, halogen, hydroxyl, nitro, C1-C6 alkyl, C1-C6 alkoxy, carboxy, C1-C6 trihaloalkyl and cyano.
- 50. The process of claim 41, wherein R1 is methyl, R2 is amino or n-propionylamino, R5 is H and Z is phenyl.
- 51. The process of claim 41, wherein R1 is C1-C6 alkyl and the alkene of the formula X is prepared by a process comprising:
(a) condensing a substituted phenyl aldehyde of the formula XI Y—CHO (XI) with nitromethane at a temperature between 75 to 118° C. to give a compound of the formula XII 85(b) treating the compound of the formula XII with one of:
(i) at least 3 molar equivalents of triethylborane, wherein R1 is ethyl; or (ii) at least 3 molar equivalents triethylborane and about 6 to about 20 molar equivalents of an alkyl iodide of the formula XIII R1—I (XIII).
- 52. The process of claim 51, wherein Y is 4-sulfamylphenyl or n-propionylamino-phenylsulfonyl.
- 53. The process of claim 52, wherein R1 is methyl.
- 54. The process of claim 41, wherein R1 is trifluoromethyl and the alkene of the formula X is formed by a process comprising:
(a) treating an alkyne of the formula VII 86with iodine in the presence of copper iodide to form a diiodo alkene of the formula XIV 87(b) reacting the diiodo alkene of the formula XIV with FSO2CF2CO2CH3; and (c) reducing the product of step (b) to give the alkene of the formula X wherein R1 is trifluoromethyl.
- 55. The process of claim 54, wherein the reduction in step (c) comprises treatment with zinc/silver acetate.
- 56. A process for the preparation of a compound of the formula IXb′
- 57. The process of claim 56, wherein R1 is methyl, R5 is hydrogen, R6 is ethyl, Z is phenyl and M is sodium.
- 58. A compound of the formula
- 59. The compound of claim 58, wherein R2 is amino.
- 60. The compound of claim 58, wherein R2 is C1-C6 alkanoylamino.
- 61. The compound of claim 60, wherein R2 is n-propionylamino.
Parent Case Info
[0001] This application claims the benefit of the priority of U.S. Provisional Patent Application No. 60/328,901, filed Oct. 12, 2001, the disclosure of which is hereby incorporated by reference as if fully set forth herein.
Provisional Applications (1)
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Number |
Date |
Country |
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60328901 |
Oct 2001 |
US |