Quinoline derivatives as anti-cancer agents

1. A quinoline derivative, comprising a structure of the following formula:

wherein R 1 and R 3 are independently of each other H or Br;

wherein each of R 2 , R 7 and R 8 is H;

wherein R 4 is CN, 2-(piperdin-1-yl)ethoxy, biphenyl-3-ylmethoxy, OH, OAc, or OR′, wherein R′ is a phenyl group having the following formula:

wherein R a is CH 2 or SO 2 ; R b and R c independently are H, Cl, F, OCH 3 , CH 3 , Ph, NO 2 , CF 3 or OCF 3 ;

wherein R 5 is H or COCH 3 ;

wherein R 6 is CH 3 , OH, CH 2 OH, CH 2 CH 2 Ph, CH 2 CH 3 , OBn, COOH, CHO, 3,4-dimethoxyphenethyl or a phenyl group having the following formula:

wherein R a is CH 2 NH; R b and R c independently of each other are H, C(CH 3 ) 3 , OCH 3 , OPh, COH 2 Ph or morpholinyl;

provided that when R 2 , R 5 , R 7 and R 8 are H, and R 4 is OH, then R 6 is not CH 3 ;

provided that when R 1 , R 2 , R 3 , R 7 and R 8 are H, R 6 is CH 3 , and R 4 is an alkoxy, then R 5 is not H; and

provided that when R 1 is Br, R 2 , R 3 , R 5 , R 7 and R 8 are H, and R 6 is CH 3 , then R 4 is not OH;

and salts thereof.

2. The quinoline derivative of claim 1 , wherein R 6 is selected from the group consisting of CH 3 , CH 2 OH, CH 2 CH 2 Ph, and OH; and wherein R 4 is OH, OAc or OR′ wherein R′ is a phenyl group having the following formula:

wherein R a is CH 2 or SO 2 , R b and R c independently are H, Cl, F, OCH 3 , CH 3 , Ph, NO 2 , CF 3 or OCF 3 .

3. The quinoline derivative of claim 1 , wherein R 6 is selected from the group consisting of CH 2 CH 3 , OBn, COOH and CHO; and R 4 is OH, OAc or OR′ wherein R′ is a phenyl group having the following formula:

wherein R a is CH 2 or SO 2 , R b and R c independently are H, Cl, F, OCH 3 , CH 3 , Ph, NO 2 , CF 3 or OCF 3 .

4. The quinoline derivative of claim 2 , wherein R 6 is CH 3 .

5. The quinoline derivative of claim 2 , wherein R 4 is OH; and wherein R 6 is OH.

6. The quinoline derivative of claim 3 , wherein R 4 is OAc; and wherein R 6 is COOH.

7. The quinoline derivative of claim 1 , wherein R 1 and R 3 are H; wherein R 6 is CH 3 ; and wherein R 4 is OR′ wherein R′ is a phenyl group of the following formula:

and

wherein Ra is CH 2 , Rb is H, OCH 3 , NO 2 or Ph, and Rc is H, Ph, F, Cl, OCF 3 , CF 3 , CN, OCH 3 or NO 2 .

8. The quinoline derivative of claim 7 , wherein Rb is H and Rc is OCH 3 , NO 2 , F, Cl, CF 3 or OCF 3 .

9. A quinoline derivative having a structure of the following formula:

wherein R 2 , R 5 , R 7 , and R 8 are H;

wherein R 1 and R 3 are Br;

wherein R 6 is CH 3 ; and

wherein R 4 is OAc or OH; and

wherein, when R 4 is OH and when the quinoline derivative comprises the following formula:

* represents a chiral center of the quinoline derivative;

and salts thereof.

10. A method of treating cancer in a mammal, the method comprising the step of administering to the mammal a quinoline derivative of claim 1 in an amount from about 8 to about 12 mg/kg/day body weight with a pharmaceutically acceptable carrier.

11. The method of claim 10 , wherein said quinoline derivative is administered over a continuous period of between 5 to 10 days.

12. The method of claim 10 , wherein said cancer is breast carcinoma, hepatocellulor carcinoma, or chronic myelogenous leukemia.

13. The method of claim 10 , wherein said quinoline derivative is a chiral or non-chiral tetrahydroquinoline derivative.

14. A quinoline derivative, wherein said quinoline derivative is a substituted quinoline selected from the group consisting of 5,7-dibromo-1,2,3,4-tetrahydro-2-methylquinolin-8-ol and 1,2,3,4-tetrahydro-2-(hydroxymethyl)quinolin-8-ol.

15. The quinoline derivative of claim 1 , wherein said quinoline derivative is selected from the group consisting of 2-methyl-1,2,3,4-tetrahydroquinolin-8-yl acetate, and 1-acetyl-2-methyl-1,2,3,4-tetrahydroquinoline-8-yl acetate.

16. The quinoline derivative of claim 1 , wherein said quinoline derivative is selected from the group consisting of 8-(2-(piperidin-1-yl)ethoxy)-1,2,3,4-tetrahydro-2-methylquinoline, 8-(benzyloxy)-1,2,3,4-tetrahydro-2-methylquinoline, 8-(3-nitrobenzyloxy)-1,2,3,4-tetrahydro-2-methylquinoline, 8-(4-nitrobenzyloxy)-1,2,3,4-tetrahydro-2-methylquinoline, 8-(4-methoxybenzyloxy)-1,2,3,4-tetrahydro-2-methylquinoline, 8-(3-methoxybenzyloxy)-1,2,3,4-tetrahydro-2-methylquinoline, 4-((1,2,3,4-tetrahydro-2-methylquinolin-8-yloxy)methyl)benzonitrile, 8-(biphenyl-3-ylmethoxy)-2-methyl-1,2,3,4-tetrahydroquinoline, 8-(4-(trifluoromethoxy)benzyloxy)-1,2,3,4-tetrahydro-2-methylquinoline, 8-(4-fluorobenzyloxy)-1,2,3,4-tetrahydro-2-methylquinoline, 8-(4-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydro-2-methylquinoline, 8-(4-chlorobenzyloxy)-1,2,3,4-tetrahydro-2-methylquinoline, 8-(benzyloxy)-1,2,3,4-tetrahydro-2-phenethylquinoline, 2-(3,4-dimethoxyphenethyl)-1,2,3,4-tetrahydroquinoline, 5,7-dibromo-2-methyl-8-(4-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydroquinoline, and 5,7-dibromo-2-methyl-8-(4-(trifluoromethoxy)benzyloxy)-1,2,3,4-tetrahydroquinoline.

17. The quinoline derivative of claim 1 ,

wherein R 1 and R 3 are H;

wherein R 6 is CH 3 ; and

wherein R 4 is 4-(trifluoromethyl)benzyloxy.

18. The quinoline derivative of claim 1 , wherein R 4 is OR′ wherein R′ is a phenyl group of the following formula:

and

wherein Ra is CH 2 , Rb is H, OCH 3 , NO 2 or Ph, and Rc is H, Ph, F, Cl, OCF 3 , CF 3 , CN, OCH 3 or NO 2 .

19. A method of treating cancer in a mammal, the method comprising the step of administering to the mammal a pharmaceutical composition comprising

(i) the quinoline derivative of claim 14 ; and

(ii) a pharmaceutically acceptable carrier.

20. The method according to claim 19 , wherein the step of administering comprises administering the quinoline derivative in an amount from about 8 to about 12 mg per kg body weight of the mammal.

21. The method according to claim 19 , wherein the quinoline derivative is administered to the mammal daily over a continuous period of between 5 to 10 days.

22. The method according to claim 19 , wherein the cancer is breast carcinoma, hepatocellulor carcinoma, or chronic myelogenous leukemia.