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
wherein R a , R d , m, and R 6 are as defined in the following table:
Compound
R a
R d
m
R 6
5l
2,3-(MeO) 2
8,9-(OCH 2 O)
3
imidazol-1-yl
5q
2,3-(MeO) 2
8,9-(OCH 2 O)
3
morpholin-4-yl
or a pharmaceutically acceptable salt, hydrate, or solvate thereof.
2. The compound, or pharmaceutically acceptable salt, hydrate, or solvate thereof, of claim 1 wherein the compound has the following formula:
3. The compound, or pharmaceutically acceptable salt, hydrate, or solvate thereof, of claim 1 wherein the compound has the following formula:
4. A pharmaceutical composition for treating cancer, the composition comprising:
(a) a compound or a pharmaceutically acceptable salt, hydrate, or solvate thereof, as described in claim 3 , and
(b) one or more pharmaceutically acceptable carriers, diluents, or excipients therefor.
5. A pharmaceutical composition for treating cancer, the composition comprising:
(a) a compound or a pharmaceutically acceptable salt, hydrate, or solvate thereof, as described in claim 4 , and
(b) one or more pharmaceutically acceptable carriers, diluents, or excipients therefor.
6. A process for preparing the compound of claim 1 , wherein the process comprises a compound of the formula
without isolating an intermediate product, or the process comprises reacting a compound of the formula
with a compound of the formula
cyclizing the intermediate product wherein R a and R d are as defined in claim 1 .
7. The process of claim 6 wherein the cyclizing step includes one or more acids.
8. The process of claim 6 wherein the cyclizing step includes dicyclohexylcarbodiimide.
9. A process for preparing a compound of claim 1 of the formula
the process comprising the step of reacting a compound of the formula
with an amine of the formula R 6 —(CH 2 ) m —NH 2 , wherein R a , R d , m, and R 6 are as defined in claim 1 .