Pyridinyl quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors

1. A compound of formula I:

or a pharmaceutically acceptable salt, enantiomer, or tautomer thereof,

wherein:

each W 1 and W 2 is independently CH, CF or N;

W 3 is independently, CR 2 or N;

U and V are independently N, CH or CR 6 ; Z is independently N or C, provided that U and V are not both N; provided that one of U, V, or Z is N; and provided that when one of U, V, or Z is N, R 1 is not H, C 1 -C 4 alkyl, or methoxy;

A is selected from the group consisting of H, D, halogen, CN, —CHO, —COOH, —COOR, —C(O)NH 2 , —C(O)NHR, R′S(O) 2 —, —O(CH 2 ) n C(O)R′, R′S(O)—, heteroaryl, —SOMe, —SO 2 Me,

B is selected from the group consisting of null, H, D, R 6 , OH, NO 2 , NH 2 , —NR 7 R 8 , CN, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, substituted aryl, C 1 -C 6 alkoxy, substituted heteroaryl, —O(CH 2 ) n R′, —(CH 2 ) n C(O)NHR, —C(O)NH 2 , —SR, OR,

—(CHR′) n S(O)R, —(CHR′) n S(O) 2 R, —COOR,

wherein X and Y are independently in each occurrence C, N, NR′, S, and O, provided that the ring containing X and Y cannot have more than 4 N or NH atoms or more than one S or O atoms, and wherein the S and O are not contiguous; provided that B is null when Z is N;

R and R′ at each occurrence are independently selected from the group consisting of H, OH, CN, —CH 2 CN, halogen, —NR 7 R 8 , CHCF 2 , CF 3 , C 1 -C 6 alkyl, R 7 S(O) 2 —, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkylalkyl, 3- to 8-membered heterocyclyl, aryl, and heteroaryl, wherein each R is optionally substituted with one or more substituents selected from the group consisting of OH, halogen, C 1 -C 6 alkoxy, NH 2 , R 7 S(O) 2 —, CN, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, heteroaryl, and R 7 S(O)—, and wherein each R′ is optionally substituted with one or more substituents selected from the group consisting of fluoro and —S(O) 2 CH 3 ;

R 1 is independently H, OH, CN, halogen, CHCF 2 , CF 3 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkenyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, or heteroaryl, wherein each C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, or heteroaryl is optionally substituted one or more times with substituents selected from the group consisting of halogen, OH, NH 2 , CN, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;

R 2 is independently H, OH, CN, halogen, CF 3 , CHF 2 , benzyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, NH 2 , —O(CH 2 ) n R′, —O(CH 2 ) n C(O)NHR′, —O(CH 2 ) n C(O)R′, NHR 7 , —N(R 7 )(R 8 ), NHC(O)R 7 , NHS(O)R 7 , NHS(O) 2 R 7 , NHC(O)OR 7 , NHC(O)NHR 7 , —S(O) 2 NHR 7 , NHC(O)N(R 8 )R 7 , OCH 2 R 7 , CHRR′ or OCHR′R 7 , wherein C 1 -C 6 alkyl, C 1 -C 6 alkoxy is optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl substituted with one or more halogen, 3- to 8-membered heterocyclyl, aryl, -heteroaryl-C(O)NH 2 , and heteroaryl;

or R 1 and R 2 can combine to form a C 4 -C 6 cycloalkyl or a 3- to 8-membered heterocyclyl containing at least one atom selected from the group consisting of N, O, and S;

R 3 is H, D, C 1 -C 6 alkyl, or; —OH,

R 4 and R 5 are independently H, D, halogen, CH 2 OH, C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with halogen, or R 4 and R 5 when combined can form a C 3 -C 5 cycloalkyl or C 3 -C 5 heterocyclyl;

R 6 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted with halogen, C 1 -C 6 alkoxy, C 1 -C 6 alkoxy substituted with one or more halogen, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, or heteroaryl;

R 7 and R 8 are independently H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, and heteroaryl; or when combined R 7 and R 8 can form a 3- to 8-membered heterocyclyl or heteroaryl ring;

n is 0, 1, or 2; and

r is 0, 1, or 2.

2. The compound of claim 1 having the formula I:

or a pharmaceutically acceptable salt, enantiomer, or tautomer thereof,

wherein:

each W 1 and W 2 is independently CH, CF or N;

W 3 is independently, CR 2 or N;

U and V are independently N, CH or CR 6 ; Z is independently N or C. provided that U and V are not both N; provided that one of U, V, or Z is N; and provided that when one of U, V, or Z is N, R 1 is not H, C 1 -C 4 alkyl, or methoxy;

A is selected from the group consisting of H, D, halogen, CN, —CHO, —COOH, —COOR, —C(O)NH 2 , —C(O)NHR, R′S(O) 2 -, —O(CH 2 ) n C(O)R′, R′S(O)—, heteroaryl, —SOMe, —SO 2 Me,

B is selected from the group consisting of null, H, D, R 6 , OH, NO 2 , NH 2 , —NR 7 R 8 , CN, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, substituted aryl, C 1 -C 6 alkoxy, substituted heteroaryl, —O(CH 2 ) n R′, —C(CH 2 ) n C(O)NHR, —C(O)NH 2 , —SR, OR, —(CHR′) n S(O)R, —(CHR′) n S(O) 2 R, —COOR,

wherein X and Y are independently in each occurrence, C, N, NR′, S, and O, provided that the ring containing X and Y cannot have more than 4 N or NH atoms or more than one S or O atoms, and wherein the S and O are not contiguous; provided that B is null when Z is N;

R and R′ at each occurrence are independently selected from the group consisting of H, OH, CN, —CH 2 CN, halogen, —NR 7 R 8 , CHCF 2 , CF 3 , C 1 -C 6 alkyl, R 7 S(O) 2 -, C 1 -C 6 alkoxy, C 1 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkylalkyl, 3- to 8-membered heterocyclyl, aryl, and heteroaryl, wherein each R is optionally substituted with one or more substituents selected from the group consisting of OH, halogen, C 1 -C 6 alkoxy, NH 2 , R 7 S(O) 2 -, CN, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, heteroaryl, and R 7 S(O)-;

R 1 is independently H, OH, CN, halogen, CHCF 2 , CF 3 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkenyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, or heteroaryl, wherein each C 1 C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 C 8 cycloalkyl, 3- to 8-membered heteroctclyl, aryl, or heteroary is optionally substituted one or more times with substituents selected from the group consisting of halogen, OH, NH 2 , CN, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;

R 2 is independently H, OH, CN, halgen, CF 3 , CHF 2 , benzyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, NH 2 , —O(CH 2 ) n R′, —O(CH 2 ) n C(O)NHR′, —O(CH 2 ) n C(O)R′, NHR 7 , —N(R 7 )(R 8 ), NHC(O)R 7 , NHS(O)R 7 , NHS(O) 2 R 7 , NHC(O)OR 7 , NHC(O)NHR 7 , —S(O) 2 NHR 7 , NHC(O)N(R 8 )R 7 , OCH 2 R 7 , CHRR′ or OCHR′R 7 , wherein C 1 -C 6 alkyl, C 1 -C 6 alkoxy optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl substituted with one or more halogen, 3- to 8-membered heterocyclyl, aryl, -heteroaryl-C(O)NH 2 , and heteroaryl;

or R 1 and R 2 can combine to form a C 4 -C 6 cycloalkyl or a 3- to 8-membered heterocyclyl containing at least one atom selected from the group consisting of N, O, and S;

R 3 is H, D, C 1 -C 6 alkyl, or; —OH,

R 4 and R 5 are independently H, D, halogen, CH 2 OH, C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with halogen, or R 4 and R 5 when combined can form a C 3 -C 5 heterocyclyl;

R 6 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted with halogen, C 1 -C 6 alkoxy, C 1 -C 6 alkoxy substituted with one or more halogen, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, or heteroaryl;

R 7 and R 8 are independently H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl or heteroaryl ring;

n is 0, 1, or 2; and

r is 0, or 2.

3. The compound of claim 2 , wherein A is CN.

4. The compound of claim 3 , wherein B is C 1 -C 6 alkoxy or C 1 -C 6 alkyl.

5. The compound of claim 4 , wherein B is methoxy.

6. The compound of claim 4 , wherein B is methyl.

7. The compound of claim 3 , wherein U is N or V is N.

8. The compound of claim 2 , wherein A is H or F.

9. The compound of claim 8 , wherein B is

10. The compound of claim 8 , wherein B is

11. The compound of claim 10 , wherein R is methyl, ethyl, and cyclopropyl.

12. The compound of claim 8 , wherein B is

13. The compound of claim 8 , wherein B is

14. The compound of claim 8 , wherein B is

15. The compound of claim 8 , wherein B is

16. The compound of claim 2 , wherein R 4 and R 5 are H.

17. The compound of claim 2 , wherein R 4 is H and R 5 is methyl.

18. The compound of claim 2 , wherein R 4 is H and R 5 is (S)-methyl.

19. The compound of claim 2 , wherein R 4 and R 5 are halogen.

20. The compound of claim 2 , wherein R 4 is F and R 5 is methyl.

21. The compound of claim 2 , wherein R 4 and R 5 can combine to form a C 3 -C 5 cycloalkyl.

22. The compound of claim 2 , wherein W 1 , W 2 , and W 3 are CH, or CF.

23. The compound of claim 2 wherein W 1 or W 3 is N.

24. The compound of claim 2 , wherein R 1 is halogen.

25. The compound of claim 2 , wherein R 2 is H, halogen, or C 1 -C 6 alkoxy.

26. The compound of claim 2 , wherein R 2 is C 1 -C 6 alkoxy substituted with heteroaryl or 3- to 8-membered heterocyclyl.

27. The compound of claim 26 , wherein R 1 is chloro.

28. The compound of claim 1 wherein the compound is:

6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methoxypyridine-3-carbonitrile;

6-{[(1S)-1-(6-chloro-1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methoxypyridine-3-carbonitrile;

6-{[(1R)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methoxypyridine-3-carbonitrile;

6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile;

6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methylpyridine-3-carbonitrile;

6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methoxypyridine-3-carbonitrile;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-6-methoxypyridine-2-carbonitrile;

6-{[(1R)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino-}2-methylpyridine-3-carbonitrile;

6-{[1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile;

6-chloro-3-[(1S)-1-{[4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[6-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[6-methyl-4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(4,4-dimethyl-2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[3-fluoro-4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[3-methyl-4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-fluoro-6-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[6-fluoro-4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[1-({4-[(4S)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]pyridin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({6-[(4S)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]pyridin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1R)-1-({6-[(4 S)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]pyridin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6{[1-(6-chloro-7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile;

6-{[(1S)-1-(6-chloro-7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile;

6-{[(1S)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile;

6-{[1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile;

6-{[(1S)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methoxypyridine-3-carbonitrile;

6-{[(1S)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methoxypyridine-3-carbonitrile;

6-{[(1S)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methylpyridine-3-carbonitrile;

6-{[(1S)-1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}-2-methylpyridine-3-carbonitrile;

6-({1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-3-yl]ethyl}amino)-2-methylpyridine-3-carbonitrile;

6-[(1-{6-chloro-7-[(3,3-difluorocyclobutyl)methoxy]-2-oxo-1,2-dihydroquinolin-3-yl}ethyl)amino]-2-methylpyridine-3-carbonitrile;

6-{[1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)cyclopropyl]amino}-2-methylpyridine-3-carbonitrile;

6-{[2-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)propan-2-yl]amino}-2-methylpyridine-3-carbonitrile;

6-chloro-3-[(1S)-1-({4-[(2-hydroxyethyl)amino]-6-methylpyridin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-3-fluoropyridin-4-yl)acetamide;

2-(6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridin-2-yl)-1λ 6 ,2-thiazolidine-1,1-dione;

6-chloro-3-[(1S)-1-({3-fluoro-4-[(2-hydroxyethyl)amino]pyridin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[3-fluoro-4-(1H-imidazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[3-fluoro-4-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(1,3-dimethyl-1H-pyrazol-5-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(1,5-dimethyl-1H-pyrazol-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(1H-pyrazol-5-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[3-fluoro-4-(1-methyl-1H-pyrrol-2-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({4-[1-(2-methylpropyl)-1H-pyrazol-5-yl]pyridin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({4-[1-(propan-2-yl)-1H-pyrazol-5-yl]pyridin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(1,5-dimethyl-1H-pyrazol-4-yl)-3-fluoropyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[3-fluoro-4-(4-methylthiophen-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({4-[1-(oxan-2-yl)-1H-pyrazol-5-yl]pyridin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(4-methylthiophen-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(1-methyl-1H-pyrazol-5-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({4-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyridin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(3,5-dimethyl-1H-pyrazol-4-yl)-3-fluoropyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(1,3-dimethyl-1H-pyrazol-5-yl)-3-fluoropyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[3-fluoro-4-(1-methyl-1H-pyrazol-5-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(dimethyl-1,2-oxazol-4-yl)-3-fluoropyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({3-fluoro-4-[1-(oxan-2-yl)-1H-pyrazol-5-yl]pyridin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({3-fluoro-4-[1-(2-methylpropyl)-1H-pyrazol-5-yl]pyridin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({3-fluoro-4-[1-(propan-2-yl)-1H-pyrazol-5-yl]pyridin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-2-methylpyridine-3-carbonitrile;

6-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-4-methylpyridine-3-carbonitrile;

6-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-2-(trifluoromethyl)pyridine-3-carbonitrile;

5-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-6-methoxypyridine-2-carbonitrile;

2-chloro-6-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}pyridine-3-carbonitrile;

6-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-2-(2-oxo-1,3-oxazolidin-3-yl)pyridine-3-carbonitrile;

6-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-2-[2-(propan-2-yl)pyrrolidin-1-yl]pyridine-3-carbonitrile;

6-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-2-[methyl(2-methylpropyl)amino]pyridine-3-carbonitrile;

6-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-2-methoxypyridine-3-carbonitrile;

6-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}pyridine-3-carbonitrile;

6-chloro-3-({[3-(propan-2-yl)pyridin-2-yl]amino}methyl)-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(4,6-dimethylpyridin-2-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(4-methoxypyridin-2-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(5-fluoropyridin-2-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

2-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}pyridine-4-carbonitrile;

methyl 6-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}pyridine-2-carboxylate;

6-chloro-3-{[(4-methylpyridin-2-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(5-chloropyridin-2-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(2-hydroxypyridin-3-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-({[5-(trifluoromethyl)pyridin-2-yl]amino}methyl)-1,2-dihydroquinolin-2-one;

5-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}pyridine-2-carbonitrile;

6-chloro-3-({[4-(trifluoromethyl)pyridin-2-yl]amino}methyl)-1,2-dihydroquinolin-2-one;

6-{[(6,7-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}pyridine-3-carbonitrile;

6-{[(6-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}pyridine-3-carbonitrile;

6-methoxy-3-{[(4-methylpyridin-2-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-{[6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-2-methylpyridine-3-carbonitrile;

6-({[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-3-yl]methyl}amino)-2-methylpyridine-3-carbonitrile or

6-[({6-chloro-7-[2-(4-methanesulfonylpiperazin-1-yl)ethoxy]-2-oxo-1,2-dihydroquinolin-3-yl}methyl)amino]-2-methylpyridine-3-carbonitrile.

29. The compound of claim 1 wherein the compound is:

Methyl N-(2-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridin-4-yl)carbamate;

2-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridine-4-carboxamide;

6-chloro-3-[(1S)-1-{[4-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridin-4-yl)acetamide;

6-chloro-3-[(1S)-1-{[4-(1H-imidazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(1,2-oxazol-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

3-[(1S)-1-{[4-(1-benzyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-6-chloro-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(1-methyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(3-methylpyridin-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridin-4-yl)-N-(2-methylpropyl)methanesulfonamide;

methyl N-(2-{[(1S)-1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}pyridin-4-yl)carbamate;

2-{[(1S)-1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}pyridine-4-carboxamide;

6-chloro-3-[(1S)-1-{[3-fluoro-4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)pyridin-2-yl]amino}ethyl]-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}pyridin-4-yl)acetamide;

6-chloro-3-[(1S)-1-{[4-(1H-imidazol-1-yl)pyridin-2-yl]amino}ethyl]-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(1,2-oxazol-4-yl)pyridin-2-yl]amino}ethyl]-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(4-methylthiophen-3-yl)pyridin-2-yl]amino}ethyl]-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-2-one;

3-[(1S)-1-{[4-(1-benzyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-6-chloro-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(1-methyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(3-methylpyridin-4-yl)pyridin-2-yl]amino}ethyl]-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}pyridin-4-yl)-N-(2-methylpropyl)methanesulfonamide;

6-{[(1S)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile;

methyl N-(2-{[(1S)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridin-4-yl)carbamate;

2-{[(1S)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridine-4-carboxamide;

6-chloro-3-[(1S)-1-{[3-fluoro-4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-7-methoxy-1,2-dihydroquinolin-2-one;

6-chloro-7-methoxy-3-[(1S)-1-{[4-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridin-4-yl)acetamide;

6-chloro-3-[(1S)-1-{[4-(1H-imidazol-1-yl)pyridin-2-yl]amino}ethyl]-7-methoxy-1,2-dihydroquinolin-2-one;

6-chloro-7-methoxy-3-[(1S)-1-{[4-(1,2-oxazol-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-7-methoxy-3-[(1S)-1-{[4-(4-methylthiophen-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

3-[(1S)-1-{[4-(1-benzyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-6-chloro-7-methoxy-1,2-dihydroquinolin-2-one;

6-chloro-7-methoxy-3-[(1S)-1-{[4-(1-methyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-7-methoxy-3-[(1S)-1-{[4-(3-methylpyridin-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridin-4-yl)-N-(2-methylpropyl)methanesulfonamide;

6-{[(1S)-1-[6-chloro-2-oxo-7-(propan-2-yloxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}-2-methylpyridine-3-carbonitrile;

methyl N-(2-{[(1S)-1-[6-chloro-2-oxo-7-(propan-2-yloxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}pyridin-4-yl)carbamate;

2-{[(1S)-1-[6-chloro-2-oxo-7-(propan-2-yloxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}pyridine-4-carboxamide;

6-chloro-3-[(1S)-1-{[3-fluoro-4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-7-(propan-2-yloxy)-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)pyridin-2-yl]amino}ethyl]-7-(propan-2-yloxy)-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-[6-chloro-2-oxo-7-(propan-2-yloxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}pyridin-4-yl)acetamide;

6-chloro-3-[(1S)-1-{[4-(1H-imidazol-1-yl)pyridin-2-yl]amino}ethyl]-7-(propan-2-yloxy)-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(1,2-oxazol-4-yl)pyridin-2-yl]amino}ethyl]-7-(propan-2-yloxy)-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(4-methylthiophen-3-yl)pyridin-2-yl]amino}ethyl]-7-(propan-2-yloxy)-1,2-dihydroquinolin-2-one;

3-[(1S)-1-{[4-(1-benzyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-6-chloro-7-(propan-2-yloxy)-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(1-methyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-7-(propan-2-yloxy)-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[4-(3-methylpyridin-4-yl)pyridin-2-yl]amino}ethyl]-7-(propan-2-yloxy)-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-[6-chloro-2-oxo-7-(propan-2-yloxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}pyridin-4-yl)-N-(2-methylpropyl)methanesulfonamide;

6-{[(1S)-1-[6-chloro-7-(cyclopropylmethoxy)-2-oxo-1,2-dihydroquinolin-3-yl]ethyl]amino}-2-methylpyridine-3-carbonitrile;

methyl N-(2-{[(1S)-1-[6-chloro-7-(cyclopropylmethoxy)-2-oxo-1,2-dihydroquinolin-3-yl]ethyl]amino}pyridin-4-yl)carbamate;

2-{[(1S)-1-[6-chloro-7-(cyclopropylmethoxy)-2-oxo-1,2-dihydroquinolin-3-yl]ethyl]amino}pyridine-4-carboxamide;

6-chloro-7-(cyclopropylmethoxy)-3-[(1S)-1-{[3-fluoro-4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-7-(cyclopropylmethoxy)-3-[(1S)-1-{[4-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-[6-chloro-7-(cyclopropylmethoxy)-2-oxo-1,2-dihydroquinolin-3-yl]ethyl]amino}pyridin-4-yl)acetamide;

6-chloro-7-(cyclopropylmethoxy)-3-[(1S)-1-{[4-(1H-imidazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-7-(cyclopropylmethoxy)-3-[(1S)-1-{[4-(1,2-oxazol-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-7-(cyclopropylmethoxy)-3-[(1S)-1-{[4-(4-methylthiophen-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

3-[(1S)-1-{[4-(1-benzyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-6-chloro-7-(cyclopropylmethoxy)-1,2-dihydroquinolin-2-one;

6-chloro-7-(cyclopropylmethoxy)-3-[(1S)-1-{[4-(1-methyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-7-(cyclopropylmethoxy)-3-[(1S)-1-{[4-(3-methylpyridin-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-[6-chloro-7-(cyclopropylmethoxy)-2-oxo-1,2-dihydroquinolin-3-yl]ethyl]amino}pyridin-4-yl)-N-(2-methylpropyl)methanesulfonamide;

6-{[(1S)-1-(6-chloro-7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile;

methyl N-(2-{[(1S)-1-(6-chloro-7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridin-4-yl)carbamate;

2-{[(1S)-1-(6-chloro-7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridine-4-carboxamide;

6-chloro-7-fluoro-3-[(1S)-1-{[3-fluoro-4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-7-fluoro-3-[(1S)-1-{[4-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-(6-chloro-7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridin-4-yl)acetamide;

6-chloro-7-fluoro-3-[(1S)-1-{[4-(1H-imidazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-7-fluoro-3-[(1S)-1-{[4-(1,2-oxazol-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-7-fluoro-3-[(1S)-1-{[4-(4-methylthiophen-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

3-[(1S)-1-{[4-(1-benzyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-6-chloro-7-fluoro-1,2-dihydroquinolin-2-one;

6-chloro-7-fluoro-3-[(1S)-1-{[4-(1-methyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-7-fluoro-3-[(1S)-1-{[4-(3-methylpyridin-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-(6-chloro-7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridin-4-yl)-N-(2-methylpropyl)methanesulfonamide;

6-{[(1S)-1-(6-chloro-8-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile;

methyl N-(2-{[(1S)-1-(6-chloro-8-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridin-4-yl)carbamate;

2-{[(1S)-1-(6-chloro-8-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridine-4-carboxamide;

6-chloro-8-fluoro-3-[(1S)-1-{[3-fluoro-4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-8-fluoro-3-[(1S)-1-{[4-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-(6-chloro-8-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyridin-4-yl)acetamide;

6-chloro-8-fluoro-3-[(1S)-1-{[4-(1H-imidazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-8-fluoro-3-[(1S)-1-{[4-(1,2-oxazol-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-8-fluoro-3-[(1S)-1-{[4-(4-methylthiophen-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

3-[(1S)-1-{[4-(1-benzyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-6-chloro-8-fluoro-1,2-dihydroquinolin-2-one;

6-chloro-8-fluoro-3-[(1S)-1-{[4-(1-methyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-8-fluoro-3-[(1S)-1-{[4-(3-methylpyridin-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

N-(2-{[(1S)-1-(6-chloro-8-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyri din-4-yl)-N-(2-methylpropyl)methanesulfonamide;

6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydro-1, 88-naphthyridin-3-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile;

methyl N-(2-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)ethyl]amino}pyridin-4-yl)carbamate;

2-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydro-1, 8-naphthyridin-3-yl)ethyl]amino}pyridine-4-carboxamide;

6-chloro-3-[(1S)-1-{[3-fluoro-4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydro-1,8-naphthyridin-2-one;

6-chloro-3-[(1S)-1-{[4-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydro-1,8-naphthyridin-2-one;

N-(2-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)ethyl]amino}pyridin-4-yl)acetamide;

6-chloro-3-[(1S)-1-{[4-(1H-imidazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydro-1,8-naphthyridin-2-one;

6-chloro-3-[(1S)-1-{[4-(1,2-oxazol-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydro-1,8-naphthyridin-2-one;

6-chloro-3-[(1S)-1-{[4-(4-methylthiophen-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydro-1,8-naphthyridin-2-one;

3-[(1S)-1-{[4-(1-benzyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-6-chloro-1,2-dihydro-1,8-naphthyridin-2-one;

6-chloro-3-[(1S)-1-{[4-(1-methyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydro-1,8-naphthyridin-2-one;

6-chloro-3-[(1S)-1-{[4-(3-methylpyridin-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydro-1,8-naphthyridin-2-one;

N-(2-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)ethyl]amino}pyridin-4-yl)-N-(2-methylpropyl)methanesulfonamide;

6-{[(1S)-1-(7-chloro-3-oxo-3,4-dihydroquinoxalin-2-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile;

methyl N-(2-{[(1S)-1-(7-chloro-3-oxo-3,4-dihydroquinoxalin-2-yl)ethyl]amino}pyridin-4-yl)carbamate;

6-chloro-3-[(1S)-1-{[3-fluoro-4-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinoxalin-2-one;

6-chloro-3-[(1S)-1-{[4-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinoxalin-2-one;

N-(2-{[(1S)-1-(7-chloro-3-oxo-3,4-dihydroquinoxalin-2-yl)ethyl]amino}pyridin-4-yl)acetamide;

6-chloro-3-[(1S)-1-{[4-(1H-imidazol-1-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinoxalin-2-one;

6-chloro-3-[(1S)-1-{[4-(1,2-oxazol-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinoxalin-2-one

6-chloro-3-[(1S)-1-{[4-(4-methylthiophen-3-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinoxalin-2-one;

3-[(1S)-1-{[4-(1-benzyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-6-chloro-1,2-dihydroquinoxalin-2-one;

6-chloro-3-[(1S)-1-{[4-(1-methyl-1H-imidazol-5-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinoxalin-2-one;

6-chloro-3-[(1S)-1-{[4-(3-methylpyridin-4-yl)pyridin-2-yl]amino}ethyl]-1,2-dihydroquinoxalin-2-one;

N-(2-{[(1S)-1-(7-chloro-3-oxo-3,4-dihydroquinoxalin-2-yl)ethyl]amino}pyridin-4-yl)-N-(2-methylpropyl)methanesulfonamide; or

(S)-6-chloro-3-(1-((4-(5-methyl-1H-tetrazol-1-yl)pyridin-2-yl)amino)ethyl)-1,8-naphthyridin-2(1H)-one.

30. The compound of claim 2 having the Formula Ia:

31. The compound of claim 30 having the Formula Ia-1:

32. The compound of claim 30 having the Formula Ia-2:

33. The compound of claim 2 having the Formula Ib:

34. The compound of claim 33 having the Formula Ib-1:

35. The compound of claim 2 having the Formula Ic:

36. A pharmaceutical composition comprising the compound according to claim 2 and pharmaceutically acceptable carrier.

37. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 2 , wherein the disease is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

38. The method of claim 37 , wherein the disease is glioma, glioblastoma multiforme (GBM), acute myeloid leukemia (AML), chondrosarcoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS) or myeloproliferative disease (MPD).

39. The method of claim 37 , wherein administering is performed orally, parentally, subcutaneously, by injection, or by infusion.

40. A method of inhibiting mutant isocitrate dehydrogenase comprising administering to a patient in need thereof a compound of claim 2 .

41. A method of reducing alpha-ketoglutarate comprising administering to a patient in need thereof a compound of claim 2 .

42. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 30 , wherein the disease is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

43. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 31 , wherein the disease is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

44. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 32 , wherein the disease is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

45. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 33 , wherein the disease is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

46. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 34 , wherein the disease is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

47. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 35 , wherein the disease is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

48. A compound of claim 1 wherein the compound is:

6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methoxypyridine-3-carbonitrile;

6-{[(1S)-1-(6-chloro-1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methoxypyridine-3-carbonitrile;

6-{[(1R)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methoxypyridine-3-carbonitrile;

6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile; or

6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methylpyridine-3-carbonitrile.

49. A compound of claim 48 , wherein the compound is 6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methoxypyridine-3-carbonitrile.

50. A compound of claim 48 , wherein the compound is 6-{[(1S)-1-(6-chloro-1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methoxypyridine-3-carbonitrile.

51. A compound of claim 48 , wherein the compound is 6-{[(1R)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methoxypyridine-3-carbonitrile.

52. A compound of claim 48 , wherein the compound is 6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2-methylpyridine-3-carbonitrile.

53. A compound of claim 48 , wherein the compound is 6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-4-methylpyridine-3-carbonitrile.

54. A pharmaceutical composition comprising the compound according to claim 49 and pharmaceutically acceptable carrier.

55. A pharmaceutical composition comprising the compound according to claim 50 and pharmaceutically acceptable carrier.

56. A pharmaceutical composition comprising the compound according to claim 51 and pharmaceutically acceptable carrier.

57. A pharmaceutical composition comprising the compound according to claim 52 and pharmaceutically acceptable carrier.

58. A pharmaceutical composition comprising the compound according to claim 53 and pharmaceutically acceptable carrier.

59. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 49 , wherein the disease is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

60. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 50 , wherein the disease is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or 60 myeloproliferative disease (MPD).

61. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 51 , wherein the disease is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

62. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 52 , wherein the disease is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

63. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 53 , wherein the disease is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

64. A method of treating a cancer comprising administering to a patient in need thereof a compound of claim 49 , wherein the cancer is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

65. A method of treating a cancer comprising administering to a patient in need thereof a compound of claim 50 , wherein the cancer is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

66. A method of treating a cancer comprising administering to a patient in need thereof a compound of claim 51 , wherein the cancer is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

67. A method of treating a cancer comprising administering to a patient in need thereof a compound of claim 52 , wherein the cancer is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).

68. A method of treating a cancer comprising administering to a patient in need thereof a compound of claim 53 , wherein the cancer is glioma, glioblastoma multiforme, paraganglioma, acute myeloid leukemia (AML), prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, melanoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), or myeloproliferative disease (MPD).