IP Library › Granted Patent US 9,624,175

Granted Patent B2

US 9,624,175 · App. 14/858,159 · Granted Apr 18, 2017

Fused-bicyclic aryl quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors

Inventors: Jian Lin (Acton, MA); Anna Ericsson (Acton, MA); Ann-Marie Campbell (Monroe, CT); Gary Gustafson (Ridgefield, CT); Zhongguo Wang (Lexington, MA); R. Bruce Diebold (Waltham, MA); Susan Ashwell (Carlisle, MA); David R. Lancia, Jr. (Boston, MA); Justin Andrew Caravella (Cambridge, MA); Wei Lu (Newton, MA)

Assignee: FORMA THERAPEUTICS, INC.

C07D215/227 C07D401/12 C07D403/12 C07D405/12 C07D413/12 C07D417/12 C07D471/04 C07D487/04 C07D498/04

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Quick Facts

Patent No.: US 9,624,175
App. No.: 14/858,159
Granted: Apr 18, 2017
Kind: B2

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Abstract

The invention relates to inhibitors of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula: where A, B, U, V, Z, W 1 , W 2 , W 3 , and R 1 -R 6 are described herein.

Claims (461)

1. A compound of formula I:

or a pharmaceutically acceptable salt, enantiomer, hydrate, solvate, prodrug, isomer, or tautomer thereof,

wherein:

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

W 3 is CF, CR 2 , or N;

U is N or CR 6 ;

V is N or CR 9 ;

Z is N or C;

indicates a single or double bond but never two double bonds adjacent to one another in the ring in which the occurs;

A and B, A and R 6 , or B and R 9 are taken together with the atoms to which they are attached and form an aryl or a 5 to 7-membered heterocyclyl or heteroaryl ring system which can be further substituted with one or more R 10 substituents;

A and B, when not part of the fused aryl, heteroaryl, or 5 to 7-membered heterocyclyl, are each independently H, R 6 , CN, C 1 -C 6 alkyl, or C 1 -C 6 alkoxy;

R 1 is independently H, OH, CN, halogen, 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, or heteroaryl, wherein each C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 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 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, NH 2 , —O(CH 2 ) n R 7 , —O(CH 2 ) n C(O)NHR 7 , —O(CH 2 ) n C(O)R 7 , 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(R 7 )(R 8 ), or —CH(R 7 )(R 8 ), 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, 3 to 8-membered heterocyclyl substituted with one or more halogen, 3 to 8-membered heterocyclyl, aryl, -heteroaryl-C(O)NH 2 , and heteroaryl;

R 3 is H or C 1 -C 6 alkyl;

R 4 and R 5 are independently H, halogen, CH 2 OH, C 1 -C 3 alkyl, or C 1 -C 3 haloalkyl, or R 4 and R 5 when combined can form a C 3 -C 6 cycloalkyl or 3 to 8-membered heterocyclyl;

R 6 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, 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; and

R 9 is independently selected from the group consisting of H, ═O, halogen, OH, CN, —CH 2 CN, C 1 -C 6 alkyl, R 7 S(O) 2 —, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkenyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkylalkyl, 3 to 8-membered heterocyclyl, aryl, and heteroaryl, wherein alkyl, alkoxy, alkenyl, cycloalkyl, cycloalkylalkyl, 3 to 8-membered heterocyclyl, aryl, and heteroaryl are optionally further 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)—;

each R 10 is independently H, OH, CN, ═O, —COOR 11 , —C(O)R 11 , —CH 2 CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl R 11 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, C 3 -C 8 heterocyclyl, aryl, or heteroaryl; and

each R 11 is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, 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, or heteroaryl;

provided that:

(1) when A and B or A and R 6 form a 1,4-dioxane ring, R 1 and R 2 are not both methyl;

(2) when A and B or A and R 6 form a 1,3-dioxolane ring, R 1 is not H or methyl;

(3) when A and B or A and R 6 form a pyridine ring, R 1 is not H or R 2 is not methyl;

(4) when A and B or A and R 6 form a pyrazole ring, R 1 is not H, ethyl, or ethoxy;

(5) when A and B or A and R 6 form a pyrazole ring and R 1 is methyl, R 2 is not H; or

(6) when A and B or A and R 6 form a phenyl ring, R 1 is not H.

2. The compound of claim 1 having a Formula Ia:

wherein:

the C ring is pyrrolidinyl, piperidinyl, phenyl, thienyl, oxazolyl, dioxanyl, dioxolanyl, thiazolyl, isoxazolyl, isothiazolyl, pyrrolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, furyl, imidazolyl, pyridyl, pyrimidinyl, pyrrolyl, furyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, triazinyl, pyridinyl, pyrimidinyl, morpholinyl, thiomorpholinyl, oxazolonyl, oxazinonyl, dihydrooxazinonyl, imidazolonyl, pyrrolonyl, thiazolonyl, dihydropyridinonyl, dihydrothiazinedioxide, dihydrodioxinyl, dihydropyranonyl, dihydrothiophenedioxide, piperidinonyl, or dihydrooxazinony; and

R 10 is independently H, OH, CN, ═O, —COOR 11 , —C(O)R 11 , —CH 2 CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl R 11 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, C 3 -C 8 heterocyclyl, aryl, or heteroaryl; and

each R 11 is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, 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, C 3 -C 8 heterocyclyl, aryl, or heteroaryl.

3. The compound of claim 2 , wherein R 10 is methyl, ethyl, isopropyl, or isobutyl.

4. The compound of claim 1 having a Formula Ib:

wherein:

the C ring is pyrrolidinyl, piperidinyl, phenyl, thienyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, pyrrolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, furyl, imidazolyl, pyridyl, pyrimidinyl, pyrrolyl, furyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, dazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, triazinyl, pyridinyl, pyrimidinyl, morpholinyl, thiomorpholinyl, oxazolonyl, oxazinonyl, dihydrooxazinonyl, imidazolonyl, pyrrolonyl, thiazolonyl, dihydropyridinonyl, dihydrothiazinedioxide, dihydrodioxinyl, dihydropyranonyl, dihydrothiophenedioxide, piperidinonyl, or dihydrooxazinonyl;

each R 1 1 is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, 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, C 3 -C 8 heterocyclyl, aryl, or heteroaryl.

5. The compound of claim 4 , wherein R 10 is methyl, ethyl, isopropyl, or isobutyl.

6. The compound of claim 1 , wherein R 4 and R 5 are H.

7. The compound of claim 1 , wherein R 4 is H and R 5 is methyl.

8. The compound of claim 1 , wherein R 4 is H and R 5 is (S)-methyl.

9. The compound of claim 1 , wherein R 4 and R 5 are halogen.

10. The compound of claim 1 , wherein R 4 is F and R 5 is methyl.

11. The compound of claim 1 , wherein R 4 and R 5 can combine to form a C 3 -C 5 cycloalkyl.

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

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

14. The compound of claim 1 , wherein R 1 is halogen.

15. The compound of claim 14 , wherein R 1 is chloro.

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

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

18. The compound of claim 1 selected from:

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

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

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

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

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

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

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

6-chloro-3-{[(quinolin-8-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(2,3-dihydro-1-benzofuran-7-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

7-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;

7-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-3,4-dihydro-2H-1,4-benzoxazin-3-one;

3-({[2-(1H-1,3-benzodiazol-5-yl)-1H-1,3-benzodiazol-5-yl]amino}methyl)-6,7-dimethoxy-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(2-oxo-2,3-dihydro-1H-indol-6-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

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

6-chloro-3-{[(isoquinolin-8-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(3,4-dihydro-2H-1-benzopyran-8-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(6-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

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

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

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

6-chloro-3-{[(5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

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

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

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

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

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

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

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

3-{[(2,3-dihydro-1,4-benzodioxin-6-yl)amino]methyl}-6-methoxyl-1,2-dihydroquinolin-2-one;

3-{[(1H-indazol-6-yl)amino]methyl}-6,7-dimethyl-1,2-dihydroquinolin-2-one;

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

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

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

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

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

6,7-dimethyl-3-{[(2-methylquinolin-6-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

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

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

3-{[(1,3-benzothiazol-6-yl)amino]methyl}-6,7-dimethyl-1,2-dihydroquinolin-2-one;

6-tert-butyl-3-{[(1H-indazol-5-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

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

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

3-[(1S)-1-({1-acetyl-1H,2H,3H-pyrido[3,4-b][1,4]oxazin-5-yl}amino)ethyl]-6-chloro-1,2-dihydroquinolin-2-one;

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

6-chloro-3-[(1S)-1-{[1-(2-methylpropyl)-2-oxo-1H,2H,4H-pyrimido[4,5-d][1,3]oxazin-7-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({1-methyl-2-oxo-1H,2H,4H-pyrimido[4,5-d][1,3]oxazin-7-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

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

6-chloro-3-[(1S)-1-({2-oxo-1H,2H,4H-pyrimido[4,5-d][1,3]oxazin-7-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-7-methoxy-3-[1-({1-methyl-2-oxo-1H,2H,4H-pyrimido[4,5-d][1,3]oxazin-7-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

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

6-chloro-7-methoxy-3-[(1R)-1-({1-methyl-2-oxo-1H,2H,4H-pyrimido[4,5-d][1,3]oxazin-7-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-7-fluoro-3-[(1R)-1-({1-methyl-2-oxo-1H,2H,4H-pyrimido[4,5-d][1,3]oxazin-7-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({1-methyl-2-oxo-1H,2H,4H-pyrimido[4,5-d][1,3]oxazin-7-yl}amino)ethyl]-1,2-dihydro-1,8-naphthyridin-2-one;

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

6-chloro-3-[(1S)-1-({2-oxo-2H,3H-[1,3]oxazolo[4,5-d]pyrimidin-5-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

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

6-chloro-3-[(1S)-1-[(9-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl)amino]ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-[(8-oxo-8,9-dihydro-7H-purin-2-yl)amino]ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({6-oxo-5H,6H,7H-pyrrolo[2,3-d]pyrimidin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({7-methyl-6-oxo-5H,6H,7H-pyrrolo[2,3-d]pyrimidin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one; or

6-chloro-3-[(1S)-1-({7-oxo-5H,6H,7H,8H-pyrido[2,3-d]pyrimidin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one.

19. The compound of claim 1 selected from:

6-chloro-3-[(1S)-1-({1-cyclopropyl-2-oxo-1H,2H,4H-pyrimido[4,5-d][1,3]oxazin-7-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-{[2-oxo-1-(propan-2-yl)-1H,2H,4H-pyrimido[4,5-d][1,3]oxazin-7-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({1-methyl-2-oxo-1H,2H,4H-pyrido[4,3-d][1,3]oxazin-7-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-1H,3H-2λ 6 ,1,5,7-[1λ 6 ,2]thiazolo[3,4-d]pyrimidine-2,2-dione;

6-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-1H,3H-2λ 6 ,1,5-[1λ 6 ,2]thiazolo[4,3-c]pyridine-2,2-dione;

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

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

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

4-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-2H,3H-1λ 6 ,2,5-[1λ 6 ,2]thiazolo[4,5-c]pyridine-1,1-dione;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1,2,3,4-tetrahydro-2,6-naphthyridin-1-one;

6-chloro-3-[(1S)-1-({3-oxo-1H,2H,3H,4H-pyrimido[4,5-c]pyridazin-7-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({6-oxo-6H-pyrano[3,2-d]pyrimidin-2-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({1-methyl-2-oxo-1H,2H-pyrido[3,4-b]pyrazin-7-yl}amino)ethyl]-1,2-dihydroquinolin-2-one;

6-chloro-3-[(1S)-1-({3-oxo-1H,2H,3H,4H-pyrido[4,3-c]pyridazin-7-yl}amino)ethyl]-1,2-dihydroquinolin-2-one

2-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-8-methyl-7,8-dihydropteridin-7-one;

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

6-chloro-3-[(1S)-1-{[6-(2-oxo-1,3-oxazolidin-3-yl)-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

4-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-[1,3]oxazolo[4,5-c]pyridine-7-carbonitrile;

N-(4-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-[1,3]oxazolo[4,5-c]pyridin-6-yl)acetamide;

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

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

4-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1H-imidazo[4,5-c]pyridine-7-carbonitrile;

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