N-substituted indenoisoquinolines and syntheses thereof
N-Substituted indenoisoquinoline compounds, and pharmaceutical formulations of N-substituted indenoisoquinoline compounds are described. Also described are processes for preparing N-substituted indenoisoquinoline compounds. Also described are methods for treating cancer in mammals using the described N-substituted indenoisoquinoline compounds or pharmaceutical formulations thereof.
1. A compound of the formula
or a pharmaceutically acceptable salt thereof,
wherein:
m is an integer from 0 to about 6;
R 6 is selected from the group consisting of heteroaryl, heterocyclyl, and hydroxyalkylamino, wherein each of heteroaryl and heterocyclyl is optionally substituted;
R a represents 1-4 substituents each of which is independently selected from the group consisting of halo, hydroxy, and nitro; and
R d represents 2 adjacent substituents taken together with the attached carbons to form an optionally substituted heterocycle.
2. The compound of claim 1 , wherein R 6 is hydroxyalkylamino.
3. The compound of claim 1 , wherein R 6 is heteroaryl or heterocyclyl, wherein each heteroaryl and heterocyclyl is optionally substituted.
4. The compound of claim 1 wherein R a represents 1-4 substituents each independently selected from the group consisting of halo, and hydroxyl.
5. The compound of claim 1 wherein R a represents 1-4 halo substituents.
6. The compound of claim 1 , wherein R d includes a methylenedioxy group.
7. The compound of claim 1 wherein in is 3.
8. The compound of claim 1 , wherein said compound is represented by formula IV:
wherein R 3 and R 4 are each independently hydrogen, halo, hydroxy, or nitro; R 6 is heteroaryl or heterocyclyl; R 7 and R 8 are taken together with the attached carbons to form an optionally substituted heterocycle; and in is 3.
9. The compound of claim 8 , wherein said compound is represented by formula V:
10. The compound of claim 8 , wherein R 3 is hydrogen and R 4 is halo.
11. The compound of claim 8 , wherein both R 3 and R 4 are halo.
12. The compound of claim 8 , wherein said compound is
13. A compound having the following formula:
14. The compound of claim 1 having the following formula:
or a pharmaceutically acceptable salt thereof.
15. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents, and excipients.
16. A pharmaceutical composition comprising a compound of claim 13 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents, and excipients.
17. A method for treating cancer, the method comprising the step of administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need of relief from said cancer.
18. A method for treating cancer, the method comprising the step of administering a therapeutically effective amount of a compound of claim 13 , or a pharmaceutically acceptable salt thereof, to a patient in need of relief from said cancer.