Alkyl indole-3-carbinol-derived antitumor agents
View Patent ↗Compounds and methods for treating cancer or inducing apoptosis in proliferating cells. The compounds are shown in formula I: wherein X is selected from hydroxyl, thiol, and amino; Y is selected from carboxyl and sulfonyl; R 1 , R 2 , R 3 , and R 4 are selected from hydrogen, lower alkyl, and combinations thereof; R 5 , R 6 , and R 7 are selected from hydrogen, halo, ni tro, amino, methoxy, and combinations thereof; and pharmaceutically acceptable salts thereof.
1. A compound of formula I:
wherein
X is selected from hydroxyl, thiol, and amino; Y is selected from carboxyl and sulfonyl; one of R 1 , R 2 , R 3 , and R 4 is methyl and the remainder of R 1 , R 2 , R 3 , and R 4 are hydrogen; R 5 is hydrogen, R 6 is nitro, and R 7 is halo; and pharmaceutically acceptable salts thereof.
2. The compound of claim 1 , wherein X is hydroxyl.
3. The compound of claim 1 , wherein Y is sulfonyl.
4. The compound of claim 1 , wherein X is hydroxyl and Y is sulfonyl.
5. The compound of claim 1 , wherein R 2 is methyl, and R 1 , R 3 , and R 4 are hydrogen.
6. The compound of claim 5 , wherein R 7 is chloro.
7. The compound of claim 1 , wherein the compound is selected from
and pharmaceutically acceptable salts thereof.
8. The compound of claim 1 , wherein the compound is:
and pharmaceutically acceptable salts thereof.
9. A method of inducing apoptosis in proliferating cells, the method comprising the steps of contacting the proliferating cells with a therapeutically effective amount of a compound of formula I:
wherein X is selected from hydroxyl, thiol, and amino; Y is selected from carboxyl and sulfonyl; one of R 1 , R 2 , R 3 , and R 4 is methyl and the remainder of R 1 , R 2 , R 3 , and R 4 are hydrogen; R 5 is hydrogen, R 6 is nitro, and R 7 is halo; and pharmaceutically acceptable salts thereof, wherein the proliferating cells are cancer cells and the cancer is selected from prostate cancer, breast cancer, leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, and renal cancer.
10. The method of claim 9 , wherein the compound is selected from
and pharmaceutically acceptable salts thereof.
11. The method of claim 9 , wherein the compound is
and pharmaceutically acceptable salts thereof.
12. A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula I:
wherein X is selected from hydroxyl, thiol, and amino; Y is selected from carboxyl and sulfonyl; one of R 1 , R 2 , R 3 , and R 4 is methyl and the remainder of R 1 , R 2 , R 3 , and R 4 are hydrogen; R 5 is hydrogen, R 6 is nitro, and R 7 is halo; and pharmaceutically acceptable salts thereof, wherein the cancer is selected from prostate cancer, breast cancer, leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, and renal cancer.
13. The method of claim 12 , wherein the compound is selected from
and pharmaceutically acceptable salts thereof.
14. The method of claim 12 , wherein the compound is
and pharmaceutically acceptable salts thereof.