Claims
- 1. A compound having the formula (I):
- 2. The compound of claim 1, wherein X2 is fluorine.
- 3. The compound of claim 1, wherein Y1 is not a bond.
- 4. The compound of claim 1, wherein each of Y1 and Y2 independently, is —O—, —N(Rc)—, or a bond.
- 5. The compound of claim 1, wherein X1 is O.
- 6. The compound of claim 2, wherein X1 is O.
- 7. The compound of claim 6, wherein Y1 is not a bond.
- 8. The compound of claim 6, wherein each of Y1 and Y2, independently is —O—, —N(Rc)—, or a bond.
- 9. The compound of claim 1, wherein L is a C6-8 hydrocarbon chain substituted with C1-2 alkyl, C1-2 alkoxy, hydroxyl, —NH2, —NH(C1-2 alkyl), or —N(C1-2 alkyl)2.
- 10. The compound of claim 6, wherein L is a C6-8 hydrocarbon chain substituted with C1-2 alkyl, C1-2 alkoxy, hydroxyl, —NH2, —NH(C1-2 alkyl), or —N(C1-2 alkyl)2.
- 11. The compound of claim 1, wherein L is a C4-12 hydrocarbon chain.
- 12. The compound of claim 1, wherein L is a C5-12 hydrocarbon chain.
- 13. The compound of claim 1, wherein L is a C5-10 hydrocarbon chain.
- 14. The compound of claim 6, wherein L is a C5-10 hydrocarbon chain.
- 15. The compound of claim 1, wherein L is an unsaturated hydrocarbon chain containing at least two double bonds.
- 16. The compound of claim 1, wherein A is a C5-8 cycloalkenyl, 5-8 membered heteroalkenyl, phenyl, naphthyl, indanyl, or tetrahydronaphthyl optionally substituted with alkyl alkenyl, alkynyl, alkoxy, hydroxyl, hydroxylalkyl, halo, haloalkyl, or amino.
- 17. The compound of claim 6, wherein A is a C5-8 cycloalkenyl, 5-8 membered heteroalkenyl, phenyl, naphthyl, indanyl, or tetrahydronaphthyl optionally substituted with alkyl alkenyl, alkynyl, alkoxy, hydroxyl, hydroxylalkyl, halo, haloalkyl, or amino.
- 18. The compound of claim 1, wherein A is phenyl, Y1 is a bond, and L is a C6-12 hydrocarbon chain containing three double bonds and the carbon adjacent to Y1 is substituted with phenyl.
- 19. The compound of claim 6, wherein A is phenyl, Y1 is a bond, and L is a C6-12 hydrocarbon chain containing three double bonds and the carbon adjacent to Y1 is substituted with phenyl.
- 20. The compound of claim 1, wherein A is phenyl, Y1 is a bond, and L is a C3-12 hydrocarbon chain and the carbon adjacent to Y1 is substituted with two phenyl groups.
- 21. The compound of claim 6, wherein A is phenyl, Y1 is a bond, and L is a C3-12 hydrocarbon chain and the carbon adjacent to Y1 is substituted with two phenyl groups.
- 22. The compound of claim 1, wherein the compound is 1,1,1-trifluoro-8-phenyl-3,5,7-octatrien-2-one or 1,1,1-trifluoro-8-phenoxy-3,5,7-octatrien-2-one.
- 23. A method of inhibiting histone deacetylation activity in cells comprising contacting the cells with an effective amount of a compound containing a trihalomethylcarbonyl group, thereby treating one or more disorders mediated by histone deacetylase or stimulating hematopoietic cells ex vivo, and
determining whether the level of acetylated histones in the treated cells is higher than in untreated cells under the same conditions.
- 24. The method of claim 23, wherein the compound is of the formula (I):
- 25. The method of claim 23, wherein the disorder is selected from the group consisting of cancer, hemoglobinopathies, thalassemia, sickle cell anemia, cystic fibrosis, protozoan infection, spinal muscular atrophy, Huntington's disease, alpha-1 anti-trypsin, retrovirus gene vector reactivation, wound healing, hair growth, peroxisome biogenesis disorder, and adrenoleukodystrophy.
- 26. The method of claim 24, wherein the disorder is selected from the group consisting of cancer, hemoglobinopathies, thalassemia, sickle cell anemia, cystic fibrosis, protozoan infection, spinal muscular atrophy, Huntington's disease, alpha-1 anti-trypsin, retrovirus gene vector reactivation, wound healing, hair growth, peroxisome biogenesis disorder, and adrenoleukodystrophy.
- 27. The method of claim 23, wherein the disorder is cancer, cystic fibrosis, or adrenoleukodystrophy.
- 28. The method of claim 24, wherein the disorder is cancer, cystic fibrosis, or adrenoleukodystrophy.
- 29. The method of claim 23, wherein hematopoietic cells are stimulated ex vivo.
- 30. The method of claim 24, wherein hematopoietic cells are stimulated ex vivo.
- 31. The method of claim 24, wherein the compound is 1,1,1-trifluoro-5-phenyl-2-pentanone, 1,1,1-trifluoro-8-phenyl-3,5,7-octatrien-2-one, or 1,1,1-trifluoro-8-phenoxy-3,5,7-octatrien-2-one.
CLAIM OF PRIORITY
[0001] This application claims priority under 35 USC §119(e) to U.S. patent application Ser. No. 60/382,075, filed on May 22, 2002, the entire contents of which is hereby incorporated by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60382075 |
May 2002 |
US |