Claims
- 1. A compound represented by the following structural formula:
- 2. The compound of claim 1 wherein R1 and R2 are independently —H or —F.
- 3. The compound of claim 2 wherein Y is a covalent bond, —CH2—, —CHF— or —CF2—, and R3 is represented by the following structural formula:
- 4. The compound of claim 3 wherein R3 is represented by the following structural formula:
- 5. The compound of claim 2 wherein Y is —CHF— or —CF2—.
- 6. The compound of claim 2 wherein Y is —CHX— and X is a lower alkyl group.
- 7. The compound of claim 6 wherein R3 is a hydrocarbyl group optionally comprising one or more amine, ammonium, ether, thioether or phenylene linking groups and terminally substituted with —M—CR4═CHR5, —CH═CH2, —N(R7)2, —OR7, —COOR7, —Br, —Cl, —I or —N+(R7)3; M is —NR6—, —O—, —C(O)—, —C(O)O—, —C(O)NR6—, —NR6C(O)—, —(CH2)q—, or phenylene; R4 and R5 are independently —H or a C1-C5 alkyl group; each R6 is independently —H, lower alkyl, substituted lower alkyl, aryl or substituted aryl; each R7 is independently —H or a C1-C3 straight chained lower alkyl group; and q is 0 or 1.
- 8. The compound of claim 5 wherein R3 is a hydrocarbyl group optionally comprising one or more amine, ammonium, ether, thioether or phenylene linking groups and terminally substituted with —CH═CH2, —N(R7)2, —OR7, —COOR7, —Br, —Cl, —I or —N+(R7)3 and each R7 is independently —H or a C1-C3 straight chained lower alkyl group.
- 9. The compound of claim 6 wherein R3 is a phenyl group substituted with one or more groups selected from —Cl, —Br, —F, —CN, —NO2, —ORa, —N(Ra)2, —COOR, —CON(Ra)2, —CORa, —S(O)Ra, —S(0)2Ra, —S(O)2N(Ra)2, —NRaS(O)2Ra, —NRaCORa, a halogenated lower alkyl group, an aryl group, a substituted aryl group, or a halogenated alkoxy group.
- 10. The compound of claim 2 wherein Y is —CHF— or —CF2—, R3 is —(CH2)m—R8, and R8 is a substituted or unsubstituted heteroaryl group and m is an integer from 0 to 20.
- 11. The compound of claim 2 wherein Y is a covalent bond or —CH2—, R3 is —(CH2)m—R8, and R8 is a substituted or unsubstituted phenyl group and m is an integer from 7 to 18.
- 12. A polymer comprising one or more pendant phosphinyl phosphonate groups or pharmaceutically acceptable salts thereof or esters thereof.
- 13. The polymer of claim 12, wherein the phosphinyl phosphonate groups are represented by the following structural formula:
- 14. The polymer of claim 13 wherein R1 and R2 are independently —H or —F and each Rb is —H.
- 15. The polymer of claim 13 wherein the polymer is a polyacrylate, polyacrylamide, polyallylamine, polyvinylamine, polyvinylether, polyvinylester, or polystyrene.
- 16. The polymer of claim 13 wherein the polymer comprises a hydrophilic repeat unit.
- 17. The polymer of claim 15 wherein the polymer is a polyacrylamide, polymethacrylamide, polyacrylate or polymethacrylate.
- 18. The polymer of claim 12 wherein the phosphinyl phosphonate groups are represented by the following Structural Formula:
- 19. The polymer of claim 12 wherein the phosphinyl phosphonate groups are represented by the following Structural Formula:
- 20. The polymer of claim 12 wherein the polymer comprises repeat units represented by the following structural formula:
- 21. The polymer of claim 20 wherein R1 and R2 are independently —H or —F and Y is a covalent bond, —CH2—, —CHF— or —CF2—.
- 22. The polymer of claim 21 wherein A is a hydrocarbyl group optionally comprising one or more amine, ether, thioether, amide or ester linking groups.
- 23. The polymer of claim 22 wherein A is an alkylene group.
- 24. The polymer of claim 20 where the polymer is a copolymer.
- 25. The polymer of claim 24 wherein the polymer comprises a hydrophilic co-monomer.
- 26. A method of inhibiting phosphate transport in a subject in need of phosphate transport inhibition, said method comprising the step of administering to the subject an effective amount of a compound represented by the following structural formula:
- 27. The method of claim 26 wherein the subject is in need of treatment for hyperphosphatemia.
- 28. The method of claim 26 wherein the subject is in need of treatment for chronic renal failure.
- 29. The method of claim 26 wherein the subject is in need of treatment for disorders of phosphate metabolism or impaired phosphate transport function.
- 30. The method of claim 26 wherein the subject is in need of treatment for hyperparathyroidism, uremic bone disease, soft tissue calcification or osteoporosis.
- 31. The method of claim 26 wherein the method further comprises co-administering one or more phosphate sequesterants to the subject.
- 32. The method of claim 31 wherein the method further comprises co-administering sevelamer to the subject.
- 33. The method of claim 26 wherein the method further comprises co-administering one or more calcium metal ion sequestrants to the subject.
- 34. The method of claim 33 wherein the metal ion sequestrant is a calcium sequestrant.
- 35. The method of claim 26 wherein R1 and R2 are independently —H or —F and each Rb is —H.
- 36. The method of claim 35 wherein Y is a covalent bond, —CH2—, —CHF— or —CF2—, and R3 is represented by the following structural formula:
- 37. The method of claim 36 wherein R3 is represented by the following structural formula:
- 38. The method of claim 35 wherein Y is —CHX— or —CX2— and X is —H, or —F.
- 39. The method of claim 35 wherein Y is —CHX— and X is a lower alkyl group.
- 40. The method of claim 39 wherein R3 is a hydrocarbyl group optionally comprising one or more amine, ammonium, ether, thioether or phenylene linking groups and terminally substituted with —M—CR4═CHR5, —CH═CH2, —N(R7)2, —OR7, —COOR7, —Br, —Cl, —I or —N+(R7)3; M is —NR6—, —O—, —C(O)—, —C(O)O—, —C(O)NR6—, —NR6C(O)—, —(CH2)q—, or phenylene; R4 and R5 are independently —H or a C1-C5 alkyl group; each R6 is independently —H, lower alkyl, substituted lower alkyl, aryl or substituted aryl; each R7 is independently —H or a C1-C3 straight chained lower alkyl group; and q is 0 or 1.
- 41. The method of claim 38 wherein R3 is a hydrocarbyl group terminally substituted with —CH═CH2, —N(R7)2, —OR7, —COOR7, —Br, —Cl, —I or —N+(R7)3 and each R7 is independently —H or a C1-C3 straight chained lower alkyl group.
- 42. The method of claim 39 wherein R3 is a lower alkyl group.
- 43. The method of claim 35 wherein R3 is a phenyl group substituted with one or more groups selected from —Cl, —Br, —F, —CN, —NO2, —ORa, —N(Ra)2, —COOR, —CON(Ra)2, —CORa, —S(O)Ra, —S(O)2Ra, —S(O)2N(Ra)2, —NRaS(O)2Ra, —NRaCORa, a halogenated lower alkyl group, an aryl group, a substituted aryl group, or a halogenated alkoxy group.
- 44. The method of claim 35 wherein Y is a covalent bond, —CH2—, —CHF— or —CF2—, R3 is —(CH2)m—R8, and R8 is a substituted or unsubstituted heteroaryl group and m is an integer from 0 to 20.
- 45. The method of claim 35 wherein Y is —CH2—, CHF— or —CF2—, R3 is —(CH2)m—R8, and R8 is a substituted or unsubstituted phenyl group and m is an integer from 0 to 20.
- 46. A method of inhibiting phosphate transport in a subject in need of phosphate transport inhibition, said method comprising the step of administering to the subject an effective amount of a polymer comprising one or more pendant phosphinyl phosphonate groups or a pharmaceutically acceptable salt thereof or ester thereof.
- 47. The method of claim 46 wherein the subject is in need of treatment for hyperphosphotemia.
- 48. The method of claim 46 wherein the subject is in need of treatment for chronic renal failure.
- 49. The method of claim 46 wherein the subject is in need of treatment for disorders of phosphate metabolism or impaired phosphate transport function.
- 50. The method of claim 46 wherein the subject is in need of treatment for hyperparathyroidism, uremic bone disease, soft tissue calcification or osteoporosis.
- 51. The method of claim 46 wherein the method further comprises co-administering one or more phosphate sequesterants to the subject.
- 52. The method of claim 51 wherein the method further comprises co-administering sevelamer to the subject.
- 53. The method of claim 46 wherein the method further comprises co-administering one or more metal ion sequestrants to the subject.
- 54. The method of claim 53 wherein the metal ion sequestrant is a calcium sequestrant.
- 55. The method of claim 46 wherein the phosphinyl phosphonate group has the formula:
- 56. A compound containing two phosphinyl phosphonyl groups represented by Structural Formula (XV), (XVI), (XVII) or (XVIII):
RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional Application No. 60/365,940, filed on Mar. 19, 2002. The entire teachings of the above application are incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60365940 |
Mar 2002 |
US |