1-[(6,7-substituted alkoxyquinoxalinyl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives for treating tumors
The present invention relates to novel quioxaline-piperazine compounds, 1-[(6,7-substituted alkoxyquinoxalinyl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives of formula (1): and their pharmaceutically acceptable salts, a process for their preparation thereof, and compositions containing such compounds. Therapeutic methods for the treatment of hyperproliferative disorders, including cancers, by administering quioxalin-piperazine compounds are also included.
1. A method for treating tumors comprising administering a pharmaceutical composition comprising a pharmaceutically acceptable vehicle and a compound of the formula (1), or pharmaceutically acceptable salts thereof,
wherein
X and Y are independently N or C—R 7 ;
for the combination of variables R 1 and R 2 :
R 1 is H, C 1 -C 3 alkoxy, C 1 -C 3 alkyl or halogen and R 2 is F; or
R 1 is F and R 2 is H, C 1 -C 3 alkoxy, C 1 -C 3 alkyl or halogen;
R 3 is C 1 -C 3 alkyl; and
R 4 , R 5 , R 6 and R 7 are independently H, C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkylcarbonyl, cyano, nitro or halogen.
2. The method of claim 1 , wherein R 4 , R 5 , R 6 and R 7 are independently H, C 1 -C 3 alkoxy, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkylcarbonyl, cyano, nitro or halogen.
3. The method of claim 1 , wherein X and Y are independently N, C—H, C—Cl, C—CN, C—CH 3 , or C—OCH 3 .
4. The method of claim 1 , wherein X and Y are each C—R 7 .
5. The method of claim 1 , wherein R 7 is H or C 1 -C 3 alkoxy.
6. The method of claim 1 , wherein R 1 is H, OCH 3 , Cl or F and R 2 is F; or R 1 is F and R 2 is H, OCH 3 , Cl or F.
7. The method of claim 1 , wherein R 4 is H, C 1 -C 3 alkoxy, C 1 -C 3 alkyl, or halogen; R 5 is H; R 6 is H, C 1 -C 3 alkoxy, or C 1 -C 3 alkyl; and R 7 is H or C 1 -C 3 alkoxy.
8. The method of claim 1 , wherein R 1 is F and R 2 is H or CH 3 .
9. The method of claim 1 , wherein for the combination of variables R 1 and R 2 :
R 1 is H, OCH 3 , Cl or F and R 2 is F; or
R 1 is F and R 2 is H, Cl or F; and
R 3 is CH 3 ; R 4 is H, OCH 3 , CH 3 , or Cl; R 5 is H; R 6 is H, OCH 3 , or CH 3 ; and R 7 is H or OCH 3 .
10. The method of claim 1 , wherein said tumor is selected from the group consisting of: ovary tumors, breast tumors, prostate tumors, liver tumors, lung tumors, kidney tumors, colon tumors, pancreatic tumors and stomach tumors.
11. A method for treating tumors comprising administering a pharmaceutical composition comprising a pharmaceutically acceptable vehicle and a compound of the formula (1), or pharmaceutically acceptable salts thereof,
wherein
X is C—R 7 ;
Y is C—H;
for the combination of variables R 1 and R 2 :
R 1 is H, C 1 -C 3 alkoxy, C 1 -C 3 alkyl or halogen and R 2 is F; or
R 1 is F and R 2 is H, C 1 -C 3 alkoxy, C 1 -C 3 alkyl or halogen;
R 3 is C 1 -C 3 alkyl;
R 4 is H, C 1 -C 3 alkoxy, C 1 -C 3 alkyl, or halogen;
R 5 is H;
R 6 is H, C 1 -C 3 alkoxy, or C 1 -C 3 alkyl; and
R 7 is H or C 1 -C 3 alkoxy.
12. The method of claim 11 , wherein in the compound of formula (1):
for the combination of variables R 1 and R 2 :
R 1 is H, OCH 3 , Cl or F and R 2 is F; or
R 1 is F and R 2 is H, OCH 3 , Cl or F;
R 3 is CH 3 ;
R 4 is H, OCH 3 , CH 3 , or Cl;
R 5 is H;
R 6 is H, OCH 3 , or CH 3 ; and
R 7 is H or OCH 3 .
13. The method of claim 11 , wherein in the compound of formula (I):
for the combination of variables R 1 and R 2 :
R 1 is F and R 2 is H or CH 3 ;
R 3 is CH 3 ;
R 4 is H, OCH 3 , CH 3 , or Cl;
R 5 is H;
R 6 is H, OCH 3 , or CH 3 ; and
R 7 is H or OCH 3 .
14. The method of claim 11 , wherein in the compound of formula (1):
R 1 is F,
R 2 is H;
R 3 is CH 3 ;
R 4 is OCH 3 or CH 3 ;
R 5 is H;
R 6 is H, OCH 3 , or CH 3 ; and
X is C—H.
15. The method of claim 11 , wherein in the compound of formula (1):
R 1 is F,
R 2 is H;
R 3 is CH 3 ;
R 4 is OCH 3 or CH 3 ;
R 5 is H;
R 6 is OCH 3 , or CH 3 ; and
X is C—H.
16. The method of claim 11 , wherein in the compound of formula (1):
R 1 is F,
R 2 is H;
R 3 is CH 3 ;
R 4 and R 6 are both OCH 3 or CH 3 ;
R 5 is H; and
X is C—H.
17. The method of claim 11 , wherein the compound of formula (1) is selected from the group consisting of
and
pharmaceutically acceptable salts thereof.
18. The method of claim 11 , wherein said tumor is selected from the group consisting of: ovary tumors, breast tumors, prostate tumors, liver tumors, lung tumors, kidney tumors, colon tumors, pancreatic tumors and stomach tumors.
19. A method for treating tumors comprising administering a pharmaceutical composition comprising a pharmaceutically acceptable vehicle and
or a pharmaceutically acceptable salt thereof.
20. The method of claim 19 , wherein said tumor is selected from the group consisting of: ovary tumors, breast tumors, prostate tumors, liver tumors, lung tumors, kidney tumors, colon tumors, pancreatic tumors and stomach tumors.