Substituted quinoline derivatives

1. A compound of formula I:

wherein:

m is an integer from 0 to 3;

R 1 is selected from the group consisting of acylamino, carboxyl ester, and C 1 to C 5 alkyl optionally substituted with hydroxy, or halo;

R 2 is hydrogen or C 1 to C 5 alkyl;

R 3 is —C(═X)-A, wherein A is selected from the group consisting of aryl, heteroaryl, heterocyclic, and cycloalkyl, all of which may be optionally substituted with 1 to 4 substituents selected from the group consisting of C 1 to C 4 alkyl, C 1 to C 4 alkoxy, halo, hydroxy, and nitro and X is oxygen or sulfur;

R 4 is -alkylene-heterocyclic or -alkylene-NR 7 R 8 wherein alkylene is a C 1 to C 4 straight chained alkylene; R 7 and R 8 are independently selected from the group consisting of hydrogen, C 1 to C 4 alkyl, arylalkyl, heteroarylalkyl, cycloalkyl and cycloalkylalkyl;

R 5 is selected from the group consisting of L-A 1 , wherein A 1 is selected from the group consisting of aryl, heteroaryl, heterocyclic, and cycloalkyl, all of which may be optionally substituted with 1 to 4 substituents selected from the group consisting of C 1 to C 4 alkyl, C 1 to C 4 alkoxy, halo, hydroxy, and nitro and wherein L is selected from the group consisting of oxygen, —NR 9 where R 9 is hydrogen or alkyl, —S(O) q — where q is zero, one or two, and C 1 to C 5 alkylene, optionally substituted with hydroxy, halo, or acylamino; and

R 6 is selected from the group consisting of C 1 to C 5 alkyl, C 2 to C 5 alkenyl, C 2 to C 5 alkynyl, —CF 3 , C 1 to C 5 alkoxy, halo, and hydroxy;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein the compound is represented by formula II:

wherein:

A 2 and A 3 are independently selected from the group consisting of aryl, heteroaryl, heterocyclic, and cycloalkyl, all of which may be optionally substituted with 1 to 4 substituents selected from the group consisting of C 1 to C 4 alkyl, C 1 to C 4 alkoxy, halo, hydroxy, and nitro;

each R 6 is independently selected from the group consisting of C 1 to C 5 alkyl, C 2 to C 5 alkenyl, C 2 to C 5 alkynyl, -CF 3, C 1 to C 5 alkoxy, halo and hydroxyl;

R 11 is C 2 to C 3 alkyl;

R 12 and R 13 are independently selected from the group consisting of hydrogen, C 1 to C 4 alkyl, arylalkyl, heteroarylalkyl, cycloalkyl and cycloalkylalkyl;

m is an integer equal to 0 to 2;

n is an integer equal to 1 to 3; and

p is an integer equal to 1 to 4;

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein the compound is represented by formula III:

wherein:

A 2 and A 3 are independently selected from the group consisting of aryl, heteroaryl, heterocyclic, and cycloalkyl, all of which may be optionally substituted with 1 to 4 substituents selected from the group consisting of C 1 to C 4 alkyl, C 1 to C 4 alkoxy, halo, hydroxy, and nitro;

R 12 and R 13 are independently selected from the group consisting of hydrogen, C 1 to C 4 alkyl, arylalkyl, heteroarylalkyl, cycloalkyl and cycloalkylalkyl;

p is an integer equal to 1 to 4;

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein R 1 is C 1 to C 5 alkyl.

5. The compound of claim 1 , wherein R 1 is isopropyl or t-butyl.

6. The compound of claim 1 , wherein R 2 is hydrogen or methyl.

7. The compound of claim 1 , wherein X is oxygen.

8. The compound of claim 1 , wherein A is aryl.

9. The compound of claim 1 , wherein A is phenyl or naphthyl.

10. The compound of claim 1 , wherein A is heteroaryl.

11. The compound of claim 1 , wherein A is selected from the group consisting of pyridinyl, imidazolyl, furanyl, pyrazolyl, and thiazolyl.

12. The compound of claim 1 , wherein A is cycloalkyl.

13. The compound of claim 1 , wherein A is cyclohexyl.

14. The compound of claim 1 , wherein A is substituted with 1 to 4 substituents selected from the group consisting of chloro, methyl, bromo, fluoro, nitro, -CF 3 , methoxy, and t-butyl.

15. The compound of claim 1 , wherein —C(O)-A is selected from the group consisting of:

(2-chloro-6-methylpyridin-4-yl)carbonyl;

(5-methylimidazol-4-yl)carbonyl;

(naphth-2-yl)carbonyl;

(pyridin-3-yl)carbonyl;

(pyridin-4-yl) carbonyl;

3,4-difluorobenzoyl;

3,4-dimethylbenzoyl;

3,5-dimethylpyrazol-3-ylcarbonyl;

2-(3-aminopropanamido)- 4-methylbenzoyl;

2,4-difluorobenzoyl;

2,6-difluorobenzoyl;

2-chlorobenzoyl;

2-chloropyridin-3-ylcarbonyl;

2-chloropyridin-5-ylcarbonyl;

2-fluorobenzoyl;

2-methoxybenzoyl;

3,4-dichlorobenzoyl;

3-chlorobenzoyl;

3-fluoro-4-methylbenzoyl;

4-bromobenzoyl;

4-chlorobenzoyl;

4-hydroxybenzoyl;

4-methoxybenzoyl;

4-methyl-3-fluorobenzoyl;

4-methylbenzoyl;

4-nitrobenzoyl;

4-t-butylbenzoyl;

4-trifluoromethylbenzoyl;

benzoyl;

cyclohexylcarbonyl;

furan-3 -ylcarbonyl;

pyridin-2-ylcarbonyl; and

thiazol-4-ylcarbonyl.

16. The compound of claim 15 , wherein —C(O)-A is selected from the group consisting of 4-methyl-3-fluorobenzoyl, 4-methylbenzoyl, and 3,4-dimethylbenzoyl.

17. The compound of claim 1 , wherein R 4 is selected from the group consisting of:

3-(benzylamino) propyl;

3-(cyclobutylamino) propyl;

3-(cyclohexylmethylamino) propyl;

3-(diethylamino)propyl;

3-(isopropylamino) propyl;

3- [(3 -trifluoromethylpyridin-6-yl)amino]propyl;

3 -aminopropyl;

2-aminoethyl;

piperidin-3-ylmethyl; and

pyrrolidin-3 -ylmethyl.

18. The compound of claim 1 , wherein R 4 is 3-aminopropyl.

19. The compound of claim 1 , wherein R 5 is alkylene-A 1 and A 1 is aryl.

20. The compound of claim 19 , wherein R 5 is selected from the group consisting of:

benzyl;

2-methylbenzyl;

3,5-difluorobenzyl;

3-acetylaminobenzyl;

3-fluorobenzyl;

3-hydroxybenzyl;

4-chlorobenzyl;

4-difluorobenzyl; and

4-methylbenzyl.

21. The compound of claim 1 , wherein R 6 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, bromo, ethyl, vinyl, methoxy, phenyl, ethynyl, and —CF 3 .

22. The compound of claim 2 , wherein m is 1 and n is 1.

23. The compound of claim 2 , wherein R 11 is isopropyl.

24. The compound of claim 2 , wherein p is 3.

25. The compound of claim 2 , wherein R 12 and R 13 are hydrogen.

26. The compound of claim 2 , wherein A 2 is phenyl.

27. The compound of claim 3 , wherein A 2 is phenyl.

28. The compound of claim 3 , wherein p is 3.

29. The compound of claim 3 , wherein R 12 and R 13 are hydrogen.

30. A compound selected from the group consisting of:

N-(3-aminopropyl)-N- [1-(3-benzylquinolin-2-yl)- 2-methylpropyl]-3-fluoro-4-methylbenzamide;

N-(3-aminopropyl)-N-[1-(3-benzylquinolin-2-yl)-2-methylpropyl]-4-methylbenzamide;

N-(3-aminopropyl)-N-[1-(3-benzylquinolin-2-yl)-2-methylpropyl]-3,4-dimethylbenzamide;

N-(3-aminopropyl)-N-[1-(3-benzyl-7-chloroquinolin-2-yl)- 2-methylpropyl]-4-methylbenzamide;

N-(3-aminopropyl)-N-[1-(3-benzyl-7-chloroquinolin-2-yl)- 2-methylpropyl]-3-fluoro-4-methylbenzamide; and

a pharmaceutically acceptable salt thereof.

31. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

32. The composition of claim 31 further comprising at least one additional agent for the treatment of cancer.

33. The composition of claim 31 , wherein the additional agent for the treatment of cancer is selected from the group consisting of irinotecan, topotecan, gemcitabine, imatinib, trastuzumab, 5-fluorouracil, leucovorin, carboplatin, cisplatin, docetaxel, paclitaxel, tezacitabine, cyclophosphamide, vinca alkaloids, anthracyclines, rituximab, and trastuzumab.