Claims
- 1. A purified compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof
- 2. A compound of claim 1 wherein W is NR8 where R8 is hydrogen, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, aryl or alkylaryl.
- 3. A compound of claim 1 wherein:
R1, R2, and R3, are each independently H, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, aryl or alkylaryl; R4 is H, C1-C5 alkyl, C1-C5 hydroxyalkyl, C1-C5 haloalkyl, aryl, —C(═O)R6, —C(═O)OR6, or —NR6R7 where R6 and R7 are each independently hydrogen, C1-C5 aliphatic, aryl or alkylaryl; R5 is C1-C5 alkyl, C1-C5 alkoxy, C2-C5 alkenyl, C2-C5 alkynyl, aryl or alkylaryl; W is O; X is O, CH2 or a carbon-carbon bond; Y is absent or a C1-C5 alkyl, C2-C5 alkenyl, or C2-C5 alkynyl; and Ar is aryl.
- 4. A purified compound of formula (III) or a pharmaceutically acceptable salt or solvate thereof
- 5. A compound of claim 4 wherein:
R1, R2, and R3 are each independently H, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, or alkylaryl; R4 is H, C1-C5 alkyl, C1-C5 hydroxyalkyl, or C1-C5 haloalkyl; R5 is H, C1-C5 alkyl, or C1-C5 alkoxy; R8 is hydrogen or C1-C5 alkyl; X is O, CH2 or a carbon-carbon bond; and R9 is selected from the group consisting of, 108where Z is O or S, and R10 is H, methyl, hydroxymethyl, fluoromethyl, or aminomethyl.
- 6. A compound of claim 4 wherein:
R1 and R3 are methyl; R2 is H; R4 is H, methyl, ethyl, fluoromethyl, or hydroxymethyl; R5 is H, methyl, ethyl, or methoxy; R8 is hydrogen or methyl; X is O, CH2 or a carbon-carbon bond; and R9 is selected from the group consisting of 109where Z is O or S, and R10 is H, methyl, hydroxymethyl, fluoromethyl, or aminomethyl.
- 7. A purified compound of formula (IV) or a pharmaceutically acceptable salt or solvate thereof
- 8. A compound of claim 7 wherein
R1, and R3 are H; R2 is methyl; R4 is H, C1-C5 alkyl, C1-C5 hydroxyalkyl, or C1-C5 haloalkyl; R5 is H, C1-C5 alkyl, or C1-C5 alkoxy; R8 is hydrogen or C1-C5 alkyl; X is O, CH2 or a carbon-carbon bond; and R9 is selected from the group consisting of 112where Z is O or S, and R10 is H, methyl, hydroxymethyl, fluoromethyl, or aminomethyl.
- 9. A compound of claim 7 wherein:
R1, and R3 are H; R2 is methyl; R4 is H, methyl, ethyl, fluoromethyl, or hydroxymethyl; R5 is H, methyl, ethyl, or methoxy; R8 is hydrogen or methyl; X is O, CH2 or a carbon-carbon bond; and R9 is selected from the group consisting of 113where Z is O or S, and R10 is H, methyl, hydroxymethyl, fluoromethyl, or aminomethyl.
- 10. A compound of claim 7 having the formula
- 11. The compound of claim 7 hacing the formula
- 12. A purified compound of formula (VI) or a pharmaceutically acceptable salt or solvate thereof
- 13. A compound of claim 12 wherein:
R1, R2, and R3 are each independently H, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, or alkylaryl; R4 is H, C1-C5 alkyl, C1-C5 hydroxyalkyl, or C1-C5 haloalkyl; R5 is C1-C5 alkyl, or C1-C5 alkoxy; R8 is hydrogen or C1-C5 alkyl; X is O, CH2 or a carbon-carbon bond; and R9 is selected from the group consisting of 118where Z is O or S, and R10 is H, methyl, hydroxymethyl, fluoromethyl, or aminomethyl.
- 14. A compound of claim 12 wherein:
R1 and R3 are methyl; R2 is H; R4 is H, methyl, ethyl, fluoromethyl, or hydroxymethyl; R5 is methyl, ethyl, or methoxy; R8 is hydrogen or methyl; X is O, CH2 or a carbon-carbon bond; and R9 is selected from the group consisting of 119where Z is O or S, and R10 is H, methyl, hydroxymethyl, fluoromethyl, or aminomethyl.
- 15. A purified compound of formula (VII) or a pharmaceutically acceptable salt or solvate thereof
- 16. A compound of claim 15 wherein:
R1, and R3 are H; R2 is methyl; R4 is H, C1-C5 alkyl, C1-C5 hydroxyalkyl, or C1-C5 haloalkyl; R5 is C1-C5 alkyl, or C1-C5 alkoxy; R8 is hydrogen or C1-C5 alkyl; X is O, CH2 or a carbon-carbon bond; and R9 is selected from the group consisting of 122where Z is O or S, and R10 is H, methyl, hydroxymethyl, fluoromethyl, or aminomethyl.
- 17. A compound of claim 15 wherein:
R1, and R3 are H; R2 is methyl; R4 is H, methyl, ethyl, fluoromethyl, or hydroxymethyl; R5 is methyl, ethyl, or methoxy; R8 is hydrogen or methyl; X is O, CH2 or a carbon-carbon bond; and R9 is selected from the group consisting of 123where Z is O or S, and R10 is H, methyl, hydroxymethyl, fluoromethyl, or aminomethyl.
- 18. A purified compound of claim 15 of the formula
- 19. The compound of claim 15 of the formula
- 20. A purified compound of the formula
- 21. A pharmaceutical composition for the treatment of a disease or condition characterized by cellular hyperproliferation in a subject suffering therefrom, comprising a thereapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 22. A method for treating a disease or condition characterized by cellular hyperproliferation in a subject suffering therefrom, comprising administering to said subject a thereapeutically effective amount of a compound of claim 1.
- 23. The method of claim 22 wherein the disease is cancer.
- 24. A pharmaceutical composition for the treatment of a disease or condition characterized by cellular hyperproliferation in a subject suffering therefrom, comprising a thereapeutically effective amount of a compound of claim 20 and a pharmaceutically acceptable carrier.
- 25. A method for treating a disease or condition characterized by cellular hyperproliferation in a subject suffering therefrom, comprising administering to said subject a thereapeutically effective amount of a compound of claim 20.
- 26. The method of claim 25 wherein the disease is cancer.
- 27. A host cell that expresses an epothilone PKS that either lacks or has an inactive enoyl reductase domain in module 5.
- 28. The host cell of claim 27 that is a Myxobacterium xanthus cell.
- 29. The host cell of claim 27 that is a Sorangium cellulosum cell.
- 30. A method for making 10,11-dehydroepothilone D, said method comprising culturing the host cell of claim 27 under conditions such that said 10,11-dehydroepothilone D is produced.
Parent Case Info
[0001] This application claims priority under 35 U.S.C. § 120 from U.S. utility patent application Ser. Nos. 09/825,856 filed on Apr. 3, 2001 and 09/825,876 filed on Apr. 3, 2001, which claims benefit of priority from U.S. provisional application Serial No. 60/269,020 filed on Feb. 13, 2001. The contents of these applications are relied on and incorporated herein in their entirety by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60269020 |
Feb 2001 |
US |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
09825856 |
Apr 2001 |
US |
Child |
10115198 |
Apr 2002 |
US |
Parent |
09825876 |
Apr 2001 |
US |
Child |
10115198 |
Apr 2002 |
US |