Therapeutic compounds
The invention provides compounds of Formula (I): R 1 ≡R 2 (I) wherein R 1 and R 2 have any of the values or specific values defined herein, as well as compositions comprising such compounds and therapeutic methods comprising the administration of such compounds.
1. A method for treating cancer in an animal comprising administering to the animal a compound of Formula (II):
wherein: R 3 is hydroxy, mercapto, chloro, bromo, methylthio, ethylthio, methoxy, ethoxy, acetylamino, (C 1 -C 20 )alkanoyloxy, arylcarbonyloxy, or aryloxy; and R 4 is (C 4 -C 10 )alkyl, (C 2 -C 10 )alkenyl, or (C 2 -C 10 )alkynyl, which (C 4 -C 10 )alkyl, (C 2 -C 10 )alkenyl, or (C 2 -C 10 )alkynyl is optionally substituted with one or more groups independently selected from halo, hydroxy, mercapto, (C 1 -C 10 )alkoxy, (C 1 -C 10 )alkylthio, carboxy, (C 1 -C 10 )alkoxycarbonyl, aryl, heteroaryl, and NR a R b ;
each R a and R b is independently H, (C 1 -C 20 )alkyl, (C 1 -C 20 )alkanoyl, (C 2 -C 20 )alkenylcarbonyl, (C 2 -C 20 )alkynylcarbonyl, (C 1 -C 20 )alkoxy, (C 2 -C 20 )alkenyloxy, (C 2 -C 20 )alkynyloxy, or aryl-(C 1 -C 20 )alkoxycarbonyl;
or a pharmaceutically acceptable salt thereof,
wherein the cancer is breast cancer, prostate cancer, colon cancer, brain cancer, or non-small cell lung cancer.
2. The method of claim 1 wherein the cancer is a solid tumor.
3. The method of claim 1 wherein the cancer is breast cancer, colon cancer, or brain cancer.
4. The method of claim 1 wherein the animal is a human.
5. A method for inhibiting methyltransferase activity,
wherein the method comprises administering an effective amount of a compound of Formula (II):
wherein: R 3 is hydroxy, mercapto, chloro, bromo, methylthio, ethylthio, methoxy, ethoxy, acetylamino, (C 1 -C 20 )alkanoyloxy, arylcarbonyloxy, or aryloxy; and R 4 is (C 4 -C 10 )alkyl, or (C 2 -C 10 )alkynyl, which (C 4 -C 10 )alkyl, (C 2 -C 10 )alkenyl, or (C 2 -C 10 )alkynyl is optionally substituted with one or more groups independently selected from halo, hydroxy, mercapto, (C 1 -C 10 )alkoxy, (C 1 -C 10 )alkylthio, carboxy, (C 1 -C 10 )alkoxycarbonyl, aryl, heteroaryl, and NR a R b ;
each R a and R b is independently H, (C 1 -C 20 )alkyl, (C 1 -C 20 )alkanoyl, (C 2 -C 20 )alkenylcarbonyl, (C 2 -C 20 )alkynylcarbonyl, (C 1 -C 20 )alkoxy, (C 2 -C 20 )alkenyloxy, (C 2 -C 20 )alkynyloxy, or aryl-(C 1 -C 20 )alkoxycarbonyl;
or a pharmaceutically acceptable salt thereof.
6. The method of claim 5 , wherein the methyltransferase is a DNA methyltransferase.
7. The method of claim 6 , wherein the DNA methyltransferase is DNA methyltransferase 1.
8. The method of claim 5 , wherein the compound of Formula (II) is administered to a cell or cells.
9. The method of claim 5 , wherein the compound of Formula (II) is administered to an individual.
10. The method of claim 9 , wherein the individual has cancer and the cancer is breast cancer, prostate cancer, colon cancer, brain cancer, or non-small cell lung cancer.
11. The method of claim 10 , wherein the cancer is a solid tumor.
12. The method of claim 5 , wherein
R 4 is (C 4 -C 10 )alkyl or (C 2 -C 10 )alkenyl, which (C 4 -C 10 )alkyl or (C 2 -C 10 )alkenyl is optionally substituted with one or more groups independently selected from halo, hydroxy, mercapto, (C 1 -C 10 )alkoxy, (C 1 -C 10 )alkylthio, carboxy, (C 1 -C 10 )alkoxycarbonyl, aryl, heteroaryl, and NR a R b .
13. The method of claim 5 , wherein the compound of Formula (II) is 1-bromo-1,1-difluoro-4-hydroxy-5,5-dimethyl-2-hexyne.
14. The method of claim 5 , wherein the compound of Formula (II) is a compound having the formula:
15. The method of claim 1 , wherein the cancer is colon cancer or breast cancer.
16. The method of claim 1 , wherein the cancer is non-small cell lung cancer.
17. The method of claim 1 , wherein
R 4 is (C 4 -C 10 )alkyl or (C 2 -C 10 )alkenyl, which (C 4 -C 10 )alkyl or (C 2 -C 10 )alkenyl is optionally substituted with one or more groups independently selected from halo, hydroxy, mercapto, (C 1 -C 10 )alkoxy, (C 1 -C 10 )alkylthio, carboxy, (C 1 -C 10 )alkoxycarbonyl, aryl, heteroaryl, and NR a R b .
18. The method of claim 1 , wherein the compound of Formula (II) is 1-bromo-1,1-difluoro-4-hydroxy-5,5-dimethyl-2-hexyne.
19. The method of claim 1 , wherein the compound of Formula (II) is a compound having the formula: