Compounds and methods for treatment of cancer

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof; wherein

R 1 is halo, alkyl, haloalkyl, alkoxy, or hydroxyl;

R 2 and R 3 together with the nitrogen atom on which they are substituted form a substituted or unsubstituted heterocyclic ring, where substituents when present are selected from one, two or three Q 1 groups selected from alkyl, amino, alkylamino, alkoxy, hydroxyl, halo, haloalkyl, cycloalkyl, aryl, arylalkyl, alkylaryl, haloalkylaryl, heterocyclyl, heteroaryl, alkoxyalkyl, alkylcarbonyl, and alkoxycarbonyl;

R 4 and R 5 are selected as follows:

i) R 4 and R 5 are each alkyl, or

ii) R 4 and R 5 together with the nitrogen atom on which they are substituted form a substituted or unsubstituted heterocyclic ring; where substituents when present are selected from one or more Q 2 groups selected from halo, alkyl, haloalkyl, alkoxy, and hydroxyl;

R 6 is halo, alkyl, haloalkyl, alkoxy, or hydroxyl;

R 7 is hydrogen, halo, alkyl, haloalkyl, alkoxy, or hydroxyl;

n is 0 to 2;

m is 0 to 2; and

where Q 1 is optionally substituted with one, two or three groups selected from halo, alkyl, amino, alkoxy, hydroxyl, and haloalkyl.

2. The compound of claim 1 , wherein R 1 is halo or alkyl;

R 2 and R 3 together with the nitrogen atom on which they are substituted form a substituted or unsubstituted heterocyclic ring, where substituents when present are selected from one, two or three Q 1 groups selected from alkyl, amino, alkylamino, alkoxy, hydroxyl, halo, haloalkyl, cycloalkyl, aryl, arylalkyl, alkylaryl, haloalkylaryl, heterocyclyl, heteroaryl, alkoxyalkyl, alkylcarbonyl, and alkoxycarbonyl;

R 4 and R 5 are selected as follows:

i) R 4 and R 5 are each alkyl,

ii) R 4 and R 5 together with the nitrogen atom on which they are substituted form a substituted or unsubstituted 5 or 6 membered heterocyclic ring; where substituents when present are selected from one or two groups selected from halo and alkyl;

R 6 is halo, or alkyl;

R 7 is hydrogen, halo or alkyl;

n is 0 or 1; and

m is 0 or 1.

3. The compound of claim 1 , wherein R 2 and R 3 together with the nitrogen atom on which they are substituted form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl ring, where substituents when present are selected from one, two or three Q 1 groups selected from alkyl, amino, alkylamino, alkoxy, hydroxyl, halo, haloalkyl, cycloalkyl, aryl, arylalkyl, alkylaryl, haloalkylaryl, heterocyclyl, heteroaryl, alkoxyalkyl, alkylcarbonyl, and alkoxycarbonyl.

4. The compound of claim 1 , wherein Q 1 group is selected from methyl, ethyl, isopropyl, trifluoromethyl, amino, methylamino, dimethylamino, diethylamino, methoxy, methoxymethyl, hydroxyl, phenyl, trifluoromethylphenyl, cyclohexyl, piperidinyl, pyrrolidinyl, methylcarbonyl, and tert-butyloxycarbonyl.

5. The compound of claim 1 , wherein R 4 and R 5 are each methyl.

6. The compound of claim 1 , wherein the compound is of Formula IA

or a pharmaceutically acceptable salt thereof; wherein

R 2 and R 3 together with the nitrogen atom on which they are substituted form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl ring, where substituents when present are selected from one, two or three Q 1 groups selected from alkyl, amino, alkylamino, alkoxy, hydroxyl, halo, haloalkyl, cycloalkyl, aryl, arylalkyl, alkylaryl, haloalkylaryl, heterocyclyl, heteroaryl, alkoxyalkyl, alkylcarbonyl, and alkoxycarbonyl; and

R 4 and R 5 are selected as follows:

i) R 4 and R 5 are each alkyl; or

ii) R 4 and R 5 together with the nitrogen atom on which they are substituted form an unsubstituted heterocyclic ring.

7. The compound of claim 1 , wherein the compound is of Formula IB:

or a pharmaceutically acceptable salt thereof, wherein p is 0 to 3, q is 0 or 1; and Q 1 is amino, alkylamino, hydroxyl, alkoxy, or alkoxyalkyl.

8. The compound of claim 1 , wherein the compound is of Formula IC:

or a pharmaceutically acceptable salt thereof, wherein R 14 is hydrogen, alkyl, haloalkyl, aryl, arylalkyl, alkylaryl, haloalkylaryl, alkylcarbonyl, cycloalkyl, haloalkylaryl, heteroaryl, heterocyclyl or alkyloxycarbonyl; Q 1 is alkyl; and p is 0, 1 or 2.

9. The compound of claim 1 , wherein the compound is of Formula IG:

or a pharmaceutically acceptable salt thereof, wherein p is 0 to 3; Q 1 is amino, alkylamino, hydroxyl, alkoxy, or alkoxyalkyl; and R 4 and R 5 are each alkyl.

10. The compound of claim 1 , wherein the compound is of Formula IH:

or a pharmaceutically acceptable salt thereof, wherein R 14 is hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, phenyl, methylcarbonyl, cyclohexyl, trifluoromethylphenyl, pyridinyl, pyrrolidinyl, piperidinyl or tert-butyloxycarbonyl; Q 1 is methyl; p is 0, 1 or 2; and R 4 and R 5 are each methyl.

11. A compound having Formula II:

or a pharmaceutically acceptable salt thereof; wherein where R 10 and R 11 are each independently hydrogen, halo, alkyl, haloalkyl, alkoxy, or hydroxyl;

R 8 and R 9 together with the nitrogen atom on which they are substituted form a substituted or unsubstituted heterocyclic ring, where substituents when present are selected from one or more Q 3 groups selected from alkyl, amino, alkylamino, alkoxy, hydroxyl, halo, haloalkyl, cycloalkyl, aryl, arylalkyl, alkylaryl, haloalkylaryl, heterocyclyl, heteroaryl, alkoxyalkyl, alkylcarbonyl, and alkoxycarbonyl;

R 12 is halo, alkyl, haloalkyl, alkoxy, or hydroxyl;

R 13 is hydroxyl or alkoxy;

r is 0 to 2; and

where Q 3 is optionally substituted with one, two or three groups selected from halo, alkyl, amino, alkoxy, hydroxyl, and haloalkyl.

12. The compound of claim 11 , wherein R 10 and R 11 are each independently hydrogen, halo or alkyl;

R 8 and R 9 together with the nitrogen atom on which they are substituted form a substituted or unsubstituted heterocyclic ring, where substituents when present are selected from one or more Q 3 groups selected from alkyl, amino, alkylamino, alkoxy, hydroxyl, halo, haloalkyl, cycloalkyl, aryl, arylalkyl, alkylaryl, haloalkylaryl, heterocyclyl, heteroaryl, alkoxyalkyl, alkylcarbonyl, and alkoxycarbonyl;

R 12 is halo or alkyl;

R 13 is hydroxyl or alkoxy; and

r is 0 or 1.

13. The compound of claim 12 , wherein R 8 and R 9 together with the nitrogen atom on which they are substituted form a substituted or unsubstituted 5 or 6 membered heterocyclic ring, where substituents when present are selected from one, two or three Q 3 groups selected from alkyl, amino, alkylamino, alkoxy, hydroxyl, halo, haloalkyl, cycloalkyl, aryl, arylalkyl, alkylaryl, haloalkylaryl, heterocyclyl, heteroaryl, alkoxyalkyl, alkylcarbonyl, and alkoxycarbonyl.

14. The compound of claim 13 , wherein R 8 and R 9 together with the nitrogen atom on which they are substituted form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl ring.

15. The compound of claim 11 , wherein R 10 and R 11 are each hydrogen.

16. The compound of claim 1 selected from:

7-((3S,4S)-3-methoxy-4-(methylamino)pyrrolidin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

3-(piperidin-1-ylsulfonyl)-7-(4-(pyridin-2-yl)piperazin-1-yl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

7-(4-cyclohexylpiperazin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-7-(4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)-1,8-naphthyridin-4(1H)-one;

(R)-7-(3-methylpiperazin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

7-((3S,5R)-3,5-dimethylpiperazin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

(R)-7-(3-(dimethylamino)pyrrolidin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

7-(2-methylpyrrolidin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

3-(piperidin-1-ylsulfonyl)-7-(4-(pyrrolidin-1-yl)piperidin-1-yl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

(S)-7-(2-(methoxymethyl)pyrrolidin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

(R)-7-(2-(methoxymethyl)pyrrolidin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

(R)-7-(3-aminopyrrolidin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

7-(3-hydroxypyrrolidin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

7-(3-(diethylamino)pyrrolidin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

7-morpholino-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

tert-butyl 4-(5-oxo-6-(piperidin-1-ylsulfonyl)-8-(thiazol-2-yl)-5,8-dihydro-1,8-naphthyridin-2-yl)piperazine-1-carboxylate;

7-(4-methylpiperazin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

7-(4-acetylpiperazin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

7-(4-ethylpiperazin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

7-(4-isopropylpiperazin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

7-(piperazin-1-yl)-3-(piperidin-1-ylsulfonyl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

3-(piperidin-1-ylsulfonyl)-7-(pyrrolidin-1-yl)-1-(thiazol-2-yl)-1,8-naphthyridin-4(1H)-one;

7-((3S,4S)-3-methoxy-4-(methylamino)pyrrolidin-1-yl)-N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

N,N-dimethyl-4-oxo-7-(4-(pyridin-2-yl)piperazin-1-yl)-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

7-(4-cyclohexylpiperazin-1-yl)-N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-7-(4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

(R)—N,N-dimethyl-7-(3-methylpiperazin-1-yl)-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

7-((3S,5R)-3,5-dimethylpiperazin-1-yl)-N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

(R)-7-(3-(dimethylamino)pyrrolidin-1-yl)-N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

N,N-dimethyl-7-(2-methylpyrrolidin-1-yl)-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

N,N-dimethyl-4-oxo-7-(4-(pyrrolidin-1-yl)piperidin-1-yl)-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

(S)-7-(2-(methoxymethyl)pyrrolidin-1-yl)-N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

(R)-7-(2-(methoxymethyl)pyrrolidin-1-yl)-N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

(R)-7-(3-aminopyrrolidin-1-yl)-N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

7-(3-hydroxypyrrolidin-1-yl)-N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

7-(3-(diethylamino)pyrrolidin-1-yl)-N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

N,N-dimethyl-7-morpholino-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

tert-butyl 4-(6-(N,N-dimethylsulfamoyl)-5-oxo-8-(thiazol-2-yl)-5,8-dihydro-1,8-naphthyridin-2-yl)piperazine-1-carboxylate;

N,N-dimethyl-7-(4-methylpiperazin-1-yl)-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

7-(4-acetylpiperazin-1-yl)-N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

7-(4-ethylpiperazin-1-yl)-N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

7-(4-isopropylpiperazin-1-yl)-N,N-dimethyl-4-oxo-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide;

N,N-dimethyl-4-oxo-7-(piperazin-1-yl)-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide; and

N,N-dimethyl-4-oxo-7-(pyrrolidin-1-yl)-1-(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-sulfonamide.

17. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

18. The compound of claim 11 selected from:

3-((3S,4S)-3-methoxy-4-(methylamino)pyrrolidin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

(S)-3-(3-(dimethylamino)pyrrolidin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

(S)-3-(3-aminopyrrolidin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

3-(3-methoxypyrrolidin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

3-(3-hydroxypyrrolidin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

3-(3-(diethylamino)pyrrolidin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

8-oxo-3-(pyrrolidin-1-yl)-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

3-(2-methylpyrrolidin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

(R)-3-(2-(methoxymethyl)pyrrolidin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

(S)-3-(2-(methoxymethyl)pyrrolidin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

3-(4-methylpiperazin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

3-(4-ethylpiperazin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

3-(4-acetylpiperazin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

3-(4-cyclohexylpiperazin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

8-oxo-3-(piperazin-1-yl)-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

3-((3S,5R)-3,5-dimethylpiperazin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

(R)-3-(3-methylpiperazin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

8-oxo-5-thiazol-2-yl)-3-(4-(4-trifluoromethyl)phenyl)piperazin-1-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

3-(4-isopropylpiperazin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

3-morpholino-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

8-oxo-3-(4-(pyridin-2-yl)piperazin-1-yl)-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid;

8-oxo-3-(4-(pyrrolidin-1-yl)piperidin-1-yl)-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid; and

3-(4-tert-butoxycarbonyl)piperazin-1-yl)-8-oxo-5-(thiazol-2-yl)-5,8-dihydropyrido[3,2-b]pyrazine-7-carboxylic acid.

19. A pharmaceutical composition comprising a compound of claim 11 and a pharmaceutically acceptable carrier.