Methylenedioxybenzo [I] phenanthridine derivatives used to treat cancer

Patent metadata

Field	Value
Publication number	US-9562051-B2
Application number	US-201013255081-A
Country	US
Kind code	B2
Filing date	Mar 5, 2010
Priority date	Mar 6, 2009
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

Abstract

The invention provides compounds of formula I: wherein A, B, X, and Y have any of the values defined in the specification, as well as pharmaceutical compositions comprising such compounds, processes for preparing such compounds, and therapeutic methods for treating cancer and other topoisomerase mediated conditions.

First claim

What is claimed is:

1. A compound of formula I:

wherein:
one of A and B is —C(O)NH(CR 6 R 7 ) n CR 1 R 2 NR a R b and the other is H;
R 1 and R 2 are each independently (C 1 -C 3 ) alkyl;
R a is (C 1 -C 3 ) alkyl;
R b is (C 1 -C 3 ) alkyl;
for each CR 6 R 7 ; R 6 and R 7 are each independently H or CH 3 ;
n is 1, 2, or 3;
X is —OCH 3 and Y is —OR 3 ; or Y is —OCH 3 , and X is OR 3 ;
R 3 is H, CH 3 , —C(O)R 4 , —C(O)OR 5 or —C(O)NR c R d ;
R 4 is (C 1 -C 6 )alkyl, aryl, heteroaryl, aryl(alkyl), heteroaryl(alkyl), or (C 3 -C 6 )cycloalkyl;
R 5 is (C 1 -C 6 )alkyl, aryl, heteroaryl, aryl(alkyl), heteroaryl(alkyl), or (C 3 -C 6 )cycloalkyl; and
R c and R d are each independently H, aryl, heteroaryl, aryl(alkyl), heteroaryl(alkyl), or (C 1 -C 6 )alkyl; or R c and R d together with the nitrogen to which they are attached form a piperazino, pyrrolidino or piperidino;
or a salt thereof.

2. The compound of claim 1 wherein A is —C(O)NH(CR 6 R 7 ) n CR 1 R 2 NR a R b and B is H.

3. The compound of claim 1 wherein B is −C(O)NH(CR 6 R 7 ) n CR 1 R 2 NR a R b and A is H.

4. The compound of claim 1 wherein each CR 6 R 7 is CH 2 .

5. The compound of claim 1 wherein A is —C(O)NHCH 2 C(CH 3 ) 2 N(CH 3 ) 2 , —C(O)NH(CH 2 ) 2 C(CH 3 ) 2 N(CH 3 ) 2 or —C(O)NH(CH 2 ) 3 C(CH 3 ) 2 N(CH 3 ) 2 .

6. The compound of claim 1 wherein B is —C(O)NHCH 2 C(CH 3 ) 2 N(CH 3 ) 2 , —C(O)NH(CH 2 ) 2 C(CH 3 ) 2 N(CH 3 ) 2 or —C(O)NH(CH 2 ) 3 C(CH 3 ) 2 N(CH 3 ) 2 .

7. The compound of claim 1 wherein X is —OCH 3 and Y is —OR 3 .

8. The compound of claim 1 wherein Y is —OCH 3 and X is —OR 3 .

9. The compound of claim 7 wherein R 3 is —C(O)R 4 , —C(O)OR 5 or —C(O)NR c R d .

10. The compound of claim 9 wherein R 4 and R 5 are (C 1 -C 6 )alkyl.

11. The compound of claim 9 wherein R c and R d are each independently H or (C 1 -C 6 )alkyl.

12. The compound of claim 7 wherein R 3 is CH 3 .

13. The compound 2,3-dimethoxy-N-(2-(dimethylamino)-2-methylpropyl)-8,9-methylenedioxybenzo[i]phenanthridine-12-carboxamide;
or 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine-11-carboxylic acid 2-(dimethylamino)-2-methylpropylamide;
or 2,3-dimethoxy-N-(3-(dimethylamino)-3-methylbutyl)-8,9-methylenedioxybenzo[i]phenanthridine-12-carboxamide;
or 2,3-dimethoxy-N-(4-(dimethylamino)-3-methylpentyl)-8,9-methylenedioxybenzo[i]phenanthridine-12-carboxamide;
or 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine-11-carboxylic acid 3-(dimethylamino)-3-methylbutylamide; or
2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine-11-carboxylic acid 4-(dimethylamino)-4-methylpentylamide or a salt thereof.

14. A composition comprising a compound of formula I as described in claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, diluent or carrier.

15. The compound of claim 1 wherein n is 1.

16. The compound 2,3-dimethoxy-N-(2-(dimethylamino)-2-methylpropyl)-8,9-methylenedioxybenzo[i]phenanthridine-12-carboxamide or a salt thereof.

17. The compound 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine-11-carboxylic acid 2-(dimethylamino)-2-methylpropylamide or a salt thereof.

Assignees

• Lavoie Edmond J
• Feng Wei
• Liu Leroy F
• Univ Rutgers

Inventors

• Lavoie Edmond J
• Feng Wei
• Liu Leroy F

Classifications

• C07D491/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/4355

  the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title