17-beta-hydroxywithanolides and use thereof in treating cancer
Disclosed are compounds suitable for enhancing cancer treatment, for example, a compound of formula (I): (I) wherein R 1 is as defined herein. Also disclosed is a method of enhancing the response of cancer cells in a mammal to treatment with an apoptosis inducing ligand, a method of inducing apoptosis in cancer cells in a mammal, and a method of treating prostate cancer in mammal in need thereof comprising administration of a compound described herein.
1. A compound of formula (I):
wherein R 1 is C 3 -C 10 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, C 6 -C 10 aryl-C 1 -C 10 alkyl, C 6 -C 10 aryl-C 2 -C 10 alkenyl, monocyclic heteroaryl, bicyclic heteroaryl, monocyclic heteroaryl-C 1 -C 10 alkyl, bicyclic heteroaryl-C 1 -C 10 alkyl, or 4-alkylenyl-tetrahydro-1H-thieno[3,4-d]imidazol-2(3H)-one,
wherein the aryl or heteroaryl portion of R 1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkoxy, aryl, thioalkoxy, heterocyclyl, and nitro.
2. The compound of claim 1 , wherein R 1 is C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, C 6 -C 10 aryl-C 1 -C 10 alkyl, C 6 -C 10 aryl-C 2 -C 10 alkenyl, monocyclic heteroaryl, bicyclic heteroaryl, monocyclic heteroaryl-C 1 -C 10 alkyl, bicyclic heteroaryl-C 1 -C 10 alkyl, or 4-alkylenyl-tetrahydro-1H-thieno[3,4-d]imidazol-2(3H)-one,
wherein the aryl or heteroaryl portion of R 1 is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkoxy, aryl, thioalkoxy, heterocyclyl, and nitro.
3. The compound of claim 2 , wherein R 1 is
4. The compound of claim 2 ,
wherein R 1 is
5. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
6. A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutically acceptable carrier.
7. A pharmaceutical composition comprising a compound of claim 3 and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition comprising a compound of claim 4 and a pharmaceutically acceptable carrier.
9. The compound of claim 2 , which is selected from the group consisting of
10. A pharmaceutical composition comprising a compound of claim 9 and a pharmaceutically acceptable carrier.