Substituted norindenoisoquinolines, syntheses thereof, and methods of use
Described herein are substituted norindenoisoquinoline compounds, and pharmaceutical compositions and formulations comprising the norindenoisoquinoline compounds. Also described herein are methods for using the compounds for the treatment and/or prevention of topoisomerase mediated diseases, such as cancer.
1. A process for preparing a compound of the formula
or a pharmaceutically acceptable salt thereof,
wherein
R is dimethylamino, pyrrolidin-1-yl, 1H-imidazolyl, 4-methylpiperazin-1-yl, 4-morpholino, or N,N,N′-trimethylethylenediamino;
the process comprising the step of treating a compound of formula
with a compound of formula
and an acid; wherein
R 10 is alkyl; and
P is an aldehyde or protected acetal.
2. The process of claim 1 , wherein said acid is HCl.
3. A compound of the formula
or a pharmaceutically acceptable salt thereof, wherein
R is dimethylamino, pyrrolidin-1-yl, 1H-imidazolyl, 4-methylpiperazin-1-yl, 4-morpholino, or N,N,N′-trimethylethylenediamino.
4. The compound of claim 3 , wherein R is 1H-imidazolyl.
5. A composition comprising one or more compounds of claim 3 , and optionally one or more carriers, diluents, or excipients, or a combination thereof.
6. A method for inhibiting topoisomerase 1, the method comprising the step of contacting topoisomerase 1 with an effective amount of one or more compounds of claim 3 .