IP Library Patent Application 16628523
Patent Application
App. No. 16/628,523

NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF FIBROSIS

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Patent No.
US None
App. No.
16/628,523
Abstract

The present invention discloses compounds according to Formula I: Wherein R 1 , R 2 , L, A 1 , A 2 , A 3 , Cy and the subscript n are as defined herein. The present invention relates to antagonists compounds of sphingosine 1-phosphate (S1P) receptor, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, inflammatory diseases, respiratory diseases, autoimmune diseases, metabolic diseases, cardiovascular diseases, and/or proliferative diseases by administering the compound of the invention.

Claims (339)

1 ) A compound, or a pharmaceutically acceptable salt, or a solvate or the pharmaceutically acceptable salt of a solvate thereof, according to Formula I:

wherein

each A 1 , A 2 and A 3 is independently selected from C and N provided that A 1 , A 2 and A 3 are not simultaneously C or N;

each R 1 is independently selected from

C 1-4 alkyl,

C 1-4 alkoxy,

C 3-6 cycloalkyl,

4-7 membered monocyclic heteroaryl comprising 1, 2, or 3 heteroatoms independently selected from N, O, or S, optionally substituted with one or two ═O groups,

—S(O) 2 C 1-4 alkyl,

—CN,

—C(═O)NH 2 , and

halo;

the subscript n is 0, 1 or 2;

Cy is a 5-membered ring linked 9-membered fused 5-6 bicyclic heteroaryl, comprising 1, 2 or 3 N atoms, which heteroaryl is substituted with one R 3 group and one R 4 group, and optionally further substituted with one halo, or OH;

R 3 is C 1-6 alkoxy optionally substituted with one or more independently selected

halo,

C 1-4 alkoxy, or

C 3-7 cycloalkyl optionally substituted with one C 1-4 alkyl, halo, or —CN;

R 4a is

C 1-4 alkyl optionally substituted with one or more halo,

halo, or

—CN;

L is absent or is —CR 5a R 5b —;

R 2 is

—C(═O)OH,

—C(═O)NR 6a R 6b ,

—C(O)NHS(O) 2 —C 1-4 alkyl,

—C(O)NHS(O) 2 —C 3-7 cycloalkyl,

Cy 1 , or

—C(═O)Cy 2 ;

each R 5a and R 5b is independently selected from

H,

C 1-4 alkyl optionally substituted with one, two or three halo or —NR 8a R 8b , and

C 1-4 alkoxy;

each R 6a and R 6b is independently selected from

H,

C 1-6 alkyl optionally substituted from one more independently selected

OH,

—CN,

halo,

C 1-4 alkoxy,

monocyclic 4-6 membered heterocycloalkyl comprising one or two heteroatoms selected from N, O, and S, optionally substituted with one —CH 2 —OH

—S(O) 2 C 1-4 alkyl,

—S(O) 2 NH 2 ,

—C(O)NR 9a R 9b , or

C 3-7 cycloalkyl optionally substituted with OH, or halo;

C 1-4 alkoxy,

C 3-7 cycloalkyl optionally substituted with one or more OH, and

monocyclic 4-6 membered heterocycloalkyl comprising one or two heteroatoms selected from N, O, and S, optionally substituted with one or two oxo;

Cy 1 is

C 3-7 monocyclic cycloalkyl, optionally substituted with one —C(═O)OH,

monocyclic 4-6 membered heterocycloalkyl comprising one or two heteroatoms selected from N, O, and S, optionally substituted with one or two

C 1-4 alkyl optionally substituted with one —C(═O)OH,

Cy2 is

N-linked monocyclic 4-7 membered heterocycloalkyl comprising at least one N atom, and optionally one or two heteroatoms selected from N, O, and S, optionally substituted with one or more

OH,

Oxo,

—CN,

halo,

C 1-4 alkoxy,

C 1-4 alkyl optionally substituted with one or more independently selected

halo,

OH,

C 3-7 cycloalkyl,

—S(O) 2 C 1-4 alkyl, or

—NR 7a R 7b ; or

N-linked spirocyclic 7-9 membered heterocycloalkyl comprising at least one N atom, and optionally one or two heteroatoms selected from N, O, and S, optionally substituted with one or more halo;

each R 7a , R 7b , R 8a , R 8b , R 9a and R 9b is independently selected from H, and C 1-4 alkyl;

provided that

when L is absent, A 1 and A 2 are C, A 3 is N, and R 2 is COOH, R 3 is unsubstituted C 1-6 alkoxy or C 1-6 alkoxy substituted with halogen, then not COOH; and

when A 1 and A 2 are N, A 3 is C, and R 4a is —CH 3 then R 3 is not unsubstituted C 1-4 alkoxy.

2 ) The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein the subscript n is 0.

3 ) The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein Cy is Cy A , Cy B , Cy C , or Cy D :

4 ) The compound or pharmaceutically acceptable salt thereof according to claim 3 , wherein R 3 is —OCH 3 , —OCH 2 CH 3 , —OCF 3 , —OCH 2 CF 3 , —OCH 2 CHF 2 , —OCH 2 CH 2 OCH 3 ,

5 ) The compound or pharmaceutically acceptable salt thereof according to claim 3 , wherein R 4b is H, F, Cl or OH.

6 ) The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 4a is F, Cl, —CN, or —CF 3 .

7 ) The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is according to Formula Va, Vb, Vc, VIa, VIb, or VIc:

8 ) The compound or pharmaceutically acceptable salt thereof according to claim 3 , wherein each R 5a and R 5b is independently selected from H, —OCH 3 , —OCH 2 CH 3 , —CH 3 , —CH 2 CH 3 , —CH 3 , —CH 2 CHF 2 , —CH 2 CF 3 , and —CH 2 CH 2 —N(CH 3 ) 2 .

9 ) The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is according to Formula VIIa, VIIb, or VIIc:

10 ) The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 is —C(═O)OH, —C(O)NHS(O) 2 —CH 3 , —C(O)NHS(O) 2 —C 3-7 cycloalkyl,

11 ) The compound or pharmaceutically acceptable salt thereof, wherein the compound according to claim 1 is:

6-(2,2-difluoroethoxy)-2-[[4-oxo-3-(pyrrolidin-2-ylmethyl)phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

2-(azetidin-3-yl)-4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]phthalazin-1-one,

2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]propanoic acid,

2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-cinnolin-3-yl]propanoic acid,

1-[[6-chloro-5-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-4-oxo-cinnoline-3-carboxylic acid,

2-[4-[(5-chloro-6-ethoxy-1H-benzimidazol-2-yl)methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[6-cyano-5-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-chloro-6-(2,2-difluoroethoxy)-1H-indol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

6-(cyclopropylmethoxy)-2-[[3-[2-[(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]-2-oxo-ethyl]-4-oxo-cinnolin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

4-[[5-chloro-6-(2,2-difluoroethoxy)-1H-indol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-[[6-chloro-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)-1-oxo-phthalazine-6-carboxamide,

6-(2,2-difluoroethoxy)-2-[[3-[2-[(3S)-3-hydroxypyrrolidin-1-yl]-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

2-[(1-acetylpyrrolidin-2-yl)methyl]-4-[[5-chloro-6-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]phthalazin-1-one,

2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-cinnolin-3-yl]-N-methylsulfonyl-propanamide,

2-[1-[[5-chloro-6-(cyclopropylmethoxy)-1H-indol-2-yl]methyl]-4-oxo-cinnolin-3-yl]acetic acid,

((2R)-2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]propanoic acid),

(2S)-2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]propanoic acid,

(2S)-2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxocinnolin-3-yl]propanoic acid,

(2R)-2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxocinnolin-3-yl]propanoic acid,

(2-[1-[[5-cyano-6-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-4-oxocinnolin-3-yl]-3-(dimethylamino)propanoic acid),

2-[4-[(7-chloro-6-ethoxy-indazol-2-yl)methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-chloro-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-6-cyano-1-oxo-phthalazin-2-yl]acetic acid,

4-[[5-chloro-6-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-cyclopentyl-phthalazin-1-one,

4-[[5-chloro-6-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-cyclopropyl-phthalazin-1-one,

4-[[5-chloro-6-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-cyclobutyl-phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(cyclopropylmethyl)phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(cyclobutylmethyl)phthalazin-1-one,

4-[[5-chloro-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-6-methoxy-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-[[5-chloro-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-7-methoxy-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-[[5-chloro-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-2-cyclopropyl-phthalazin-1-one,

4-[[5-chloro-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-7-morpholino-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(THF-2-ylmethyl)phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(tetrahydropyran-2-ylmethyl)phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-[(3-methyloxetan-3-yl)methyl]phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-[(1-methyl-3-piperidyl)methyl]phthalazin-1-one,

1-[[5-chloro-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazine-6-carbonitrile,

4-[[5-chloro-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-6-methylsulfonyl-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

6-(cyclopropylmethoxy)-2-[(3-cyclopropyl-4-oxo-phthalazin-1-yl)methyl]-1H-benzimidazole-5-carbonitrile,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-[(2,2-difluorocyclopropyl)methyl]phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(3,3-dimethyl-2-oxo-butyl)phthalazin-1-one,

1-[[4-[[5-chloro-6-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]methyl]cyclopropanecarboxylic acid,

4-[[6-chloro-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-5-cyclopropyl-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

6-(2,2-Difluoro-ethoxy)-2-[3-(2-morpholin-4-yl-2-oxo-ethyl)-4-oxo-4H-cinnolin-1-ylmethyl]-3H-enzoimidazole-5-carbonitrile,

1-[5-(2,2-Difluoro-ethoxy)-6-fluoro, -1H-benzoimidazol-2-ylmethyl]-3-(2-morpholin-4-yl-2-oxo-ethyl)-1H-cinnolin-4-one,

6-(2-methoxyethoxy)-2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

6-(2,2-difluoropropoxy)-2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

7-chloro-6-(2,2-difluoroethoxy)-2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

2-[[8-cyclopropyl-3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]-6-(2,2-difluoroethoxy)-3H-benzimidazole-5-carbonitrile,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(pyrrolidin-2-ylmethyl)phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(4-piperidylmethyl)phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(pyrrolidin-3-ylmethyl)phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(3-piperidylmethyl)phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-pyrrolidin-3-yl-phthalazin-1-one,

2-(azetidin-3-ylmethyl)-4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]phthalazin-1-one,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(4-piperidyl)phthalazin-1-one,

4-[[5-chloro-6-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(morpholin-2-ylmethyl)phthalazin-1-one,

6-(2,2-difluoroethoxy)-2-[(4-oxo-3-pyrrolidin-3-yl-phthalazin-1-yl)methyl]-3H-benzimidazole-5-carbonitrile,

6-(2-methoxyethoxy)-2-[(4-oxo-3-pyrrolidin-3-yl-phthalazin-1-yl)methyl]-3H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[8-methyl-3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

4-[[6-chloro-5-(2-methoxyethoxy)-1H-benzimidazol-2-yl]methyl]-2-pyrrolidin-3-yl-phthalazin-1-one,

2-[[3-(azetidin-3-yl)-4-oxo-phthalazin-1-yl]methyl]-6-(2,2-difluoroethoxy)-3H-benzimidazole-5-carbonitrile,

2-[3-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]azetidin-1-yl]acetic acid,

2-[2-[[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]methyl]pyrrolidin-1-yl]acetic acid,

2-[3-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]pyrrolidin-1-yl]acetic acid,

6-(2,2-difluoroethoxy)-2-[[3-(1-methylpyrrolidin-3-yl)-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

2-[3-[4-[[7-cyano-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-1-oxo-phthalazin-2-yl]azetidin-1-yl]acetic acid,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-3-(dimethylamino)propanoic acid,

3-(azetidin-1-yl)-2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]propanoic acid,

2-[4-[[6-chloro-5-(2,2-difluoroethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]propanoic acid,

2-[4-[(6-chloro-5-ethoxy-1H-benzimidazol-2-yl)methyl]-8-methyl-1-oxo-phthalazin-2-yl]acetic acid,

{1-[6-Chloro-5-(2,2-difluoro-ethoxy)-1H-benzoimidazol-2-ylmethyl]-4-oxo-1,4-dihydro-cinnolin-3-yl}-acetic acid,

2-[4-[[7-cyano-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

1-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-4-oxo-quinoline-3-carboxylic acid,

2-[4-[[7-cyano-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-1-oxo-phthalazin-2-yl]propanoic acid,

2-[4-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-1-oxo-phthalazin-2-yl]propanoic acid,

1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-quinoline-3-carboxylic acid,

1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-cinnoline-3-carboxylic acid,

2-[4-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-6-fluoro-1-oxo-phthalazin-2-yl]propanoic acid,

2-[3-[4-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-1-oxo-phthalazin-2-yl]pyrrolidin-1-yl]acetic acid,

2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-cinnolin-3-yl]-2-methyl-propanoic acid,

2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-cinnolin-3-yl]acetic acid,

1-[[6-chloro-5-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-4-oxo-quinoline-3-carboxylic acid,

2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]cyclobutanecarboxylic acid,

2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-6-cyano-1-oxo-phthalazin-2-yl]propanoic acid,

2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-5,6,7,8-tetrahydrophthalazin-2-yl]propanoic acid,

2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-cinnolin-3-yl]-2-methoxy-acetic acid,

1-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]cyclopropanecarboxylic acid,

1-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-cinnolin-3-yl]cyclopropanecarboxylic acid,

2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-7-methoxy-1-oxo-phthalazin-2-yl]propanoic acid,

2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-cinnolin-3-yl]butanoic acid,

2-[1-[[6-(cyclopropylmethoxy)-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-cinnolin-3-yl]acetic acid,

2-[1-[[6-(cyclopropylmethoxy)-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-cinnolin-3-yl]propanoic acid,

2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-7-fluoro-4-oxo-cinnolin-3-yl]acetic acid,

2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-5-methyl-4-oxo-cinnolin-3-yl]acetic acid,

2-[1-[[6-(cyclopropylmethoxy)-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-cinnolin-3-yl]butanoic acid,

(1-[[5-(cyclopropylmethoxy)-6-(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]-4-oxocinnoline-3-carboxylic acid),

2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxo-5,6,7,8-tetrahydrocinnolin-3-yl]acetic acid,

(1-[[5-(cyclopropylmethoxy)-6-(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]-4-oxoquinoline-3-carboxylic acid),

2-[1-[[6-cyano-5-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-4-oxo-cinnolin-3-yl]propanoic acid,

2-[1-[[6-cyano-5-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-4-oxo-cinnolin-3-yl]acetic acid,

2-[1-[[6-bromo-5-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-4-oxo-cinnolin-3-yl]acetic acid,

1-[[5-cyano-6-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-4-oxo-cinnoline-3-carboxylic acid,

2-[4-[[6-bromo-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-chloro-6-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-5,6,7,8-tetrahydrophthalazin-2-yl]acetic acid,

2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-chloro-6-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-chloro-6-(cyclopropylmethoxy)-7-fluoro-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-chloro-6-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-5,6,7,8-tetrahydrophthalazin-2-yl]acetic acid,

2-[4-[[5-chloro-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-chloro-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-5,6,7,8-tetrahydrophthalazin-2-yl]acetic acid,

2-[4-[(5-chloro-6-methoxy-1H-benzimidazol-2-yl)methyl]-1-oxo-5,6,7,8-tetrahydrophthalazin-2-yl]acetic acid,

2-[4-[(5-chloro-6-ethoxy-1H-benzimidazol-2-yl)methyl]-1-oxo-5,6,7,8-tetrahydrophthalazin-2-yl]acetic acid,

2-[4-(6-Chloro-5-cyclopropylmethoxy-1H-benzoimidazol-2-ylmethyl)-1-oxo-1H-phthalazin-2-yl]-propionic acid,

2-[4-[[5-(cyclopropylmethoxy)-6-(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-(cyclopropylmethoxy)-6-fluoro-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

{4-[5-Chloro-6-(2,2-difluoro-ethoxy)-1H-benzoimidazol-2-ylmethyl]-1-oxo-1H-isoquinolin-2-yl}-acetic acid,

2-[4-[[6-chloro-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-5,8-difluoro-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-ethoxy-6-(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[(5-chloro-6-ethoxy-3-oxo-1H-indazol-2-yl)methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[(5-ethoxy-6-fluoro-1H-benzimidazol-2-yl)methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-(2,2-difluoroethoxy)-6-fluoro-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-chloro-6-[(1-methylcyclopropyl)methoxy]-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-chloro-6-(2,2-dimethylpropoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-chloro-6-[(1-cyanocyclopropyl)methoxy]-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-chloro-6-(cyclopropylmethoxy)-3-oxo-1H-indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[6-cyano-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[(6-chloro-5-methoxy-1H-benzimidazol-2-yl)methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[(6-bromo-5-ethoxy-indazol-2-yl)methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[(5-cyano-6-ethoxy-1H-benzimidazol-2-yl)methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[5-cyano-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-[(1S,2R)-2-hydroxycyclopentyl]acetamide,

2-[4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(1,1-dioxothian-4-yl)acetamide,

4-[[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-[(1S,2S)-2-hydroxycyclopentyl]acetamide,

N-tert-butyl-2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetamide,

4-[[5-chloro-6-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)-5,6,7,8-tetrahydrophthalazin-1-one,

2-[4-[[5-chloro-6-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-5,6,7,8-tetrahydrophthalazin-2-yl]-N-[(1S,2S)-2-hydroxycyclopentyl]acetamide,

2-[4-[[5-chloro-6-(trifluoromethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-5,6,7,8-tetrahydrophthalazin-2-yl]-N-[(1S,2S)-2-hydroxycyclopentyl]acetamide,

4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-[[5-chloro-6-(cyclopropylmethoxy)-7-fluoro-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

2-[4-[[5-chloro-6-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-cyclopentyl-acetamide,

4-[[5-chloro-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-[[6-chloro-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-5,8-difluoro-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-[[6-chloro-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)-1-oxo-phthalazine-6-carbonitrile,

4-[(5-chloro-6-ethoxy-3-oxo-1H-indazol-2-yl)methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-(6-Chloro-5-cyclopropylmethoxy-1H-benzoimidazol-2-ylmethyl)-2-(1-methyl-2-morpholin-4-yl-2-oxo-ethyl)-2H-phthalazin-1-one,

4-[[5-(2,2-difluoroethoxy)-6-fluoro-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-[(5-ethoxy-6-fluoro-1H-benzimidazol-2-yl)methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

6-(cyclopropylmethoxy)-2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

1-[6-Chloro-5-(2,2-difluoro-ethoxy)-1H-benzoimidazol-2-ylmethyl]-3-(2-morpholin-4-yl-2-oxo-ethyl)-1H-cinnolin-4-one,

4-[[5-chloro-6-(2,2-dimethylpropoxy)-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

1-[[6-chloro-2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazol-5-yl]oxymethyl]cyclopropanecarbonitrile,

1-[[6-chloro-2-[[3-[2-[(2S,6R)-2,6-dimethylmorpholin-4-yl]-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazol-5-yl]oxymethyl]cyclopropanecarbonitrile,

4-[[5-chloro-6-[(1-methylcyclopropyl)methoxy]-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

6-(2,2-difluoroethoxy)-2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-5,6,7,8-tetrahydrophthalazin-1-yl]methyl]-1H-benzimidazole-5-carbonitrile,

4-[(5-chloro-6-ethoxy-1H-benzimidazol-2-yl)methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-[[5-chloro-6-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

6-ethoxy-2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-5,6,7,8-tetrahydrophthalazin-1-yl]methyl]-1H-benzimidazole-5-carbonitrile,

4-[[6-ethoxy-5-(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-[6-Chloro-5-(2,2-difluoro-ethoxy)-1H-benzoimidazol-2-ylmethyl]-2-(2-morpholin-4-yl-2-oxo-ethyl)-2H-isoquinolin-1-one,

6-ethoxy-2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]-1H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]-1H-benzimidazole-5-carbonitrile,

4-[[5-chloro-6-(2,2-difluoropropoxy)-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-[(5-chloro-6-isobutoxy-1H-benzimidazol-2-yl)methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

4-[[5-chloro-6-(2-methoxyethoxy)-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)phthalazin-1-one,

2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]-6-(2,2,2-trifluoroethoxy)-3H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-[2-[3-(dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-[2-[(2S,6R)-2,6-dimethylmorpholin-4-yl]-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-THF-3-yl-acetamide,

4-[[5-(2,2-difluoroethoxy)-6-fluoro-1H-benzimidazol-2-yl]methyl]-2-(2-morpholino-2-oxo-ethyl)-5,6,7,8-tetrahydrophthalazin-1-one,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-methyl-N-(THF-2-ylmethyl)acetamide,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2-cyanoethyl)-N-cyclopropyl-acetamide,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2-methoxy-2-methyl-propyl)acetamide,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2-methoxyethyl)-N-methyl-acetamide,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-tetrahydropyran-3-yl-acetamide,

6-(2,2-difluoroethoxy)-2-[[3-[2-(4,4-difluoro-1-piperidyl)-2-oxo-ethyl]-4-oxo-5,6,7,8-tetrahydrophthalazin-1-yl]methyl]-1H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-[2-(3-methoxypyrrolidin-1-yl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-1H-benzimidazole-5-carbonitrile,

2-[4-[[5-cyano-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2-methoxyethyl)acetamide,

6-(2,2-difluoroethoxy)-2-[[3-[2-(4,4-difluoro-1-piperidyl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-1H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-[2-(6-oxa-9-azaspiro[3.5]nonan-9-yl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-1H-benzimidazole-5-carbonitrile,

2-[4-[[5-cyano-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)acetamide,

2-[4-[[5-cyano-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-[(2S)-3,3,3-trifluoro-2-hydroxy-propyl]acetamide,

2-[4-[[5-cyano-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2-hydroxy-3-methoxy-propyl)acetamide,

6-(2,2-difluoroethoxy)-2-[[3-[2-(4-hydroxy-1-piperidyl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-1H-benzimidazole-5-carbonitrile,

2-[4-[[5-cyano-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2,2-difluoroethyl)-N-(2-hydroxyethyl)acetamide,

2-[4-[[5-cyano-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2-cyanopropyl)-N-methyl-acetamide,

2-[4-[[5-cyano-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(cyclopropylmethyl)-N-methyl-acetamide,

2-[4-[[5-cyano-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2,2-difluoroethyl)-N-methyl-acetamide,

6-(2,2-difluoroethoxy)-2-[[3-[2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-1H-benzimidazole-5-carbonitrile,

2-[4-[[5-cyano-6-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-[[3-(hydroxymethyl)oxetan-3-yl]methyl]acetamide,

2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-5,6,7,8-tetrahydrophthalazin-1-yl]methyl]-6-(2,2,2-trifluoroethoxy)-1H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-[2-(3-hydroxy-3-methyl-pyrrolidin-1-yl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2,2-dimethylpropyl)acetamide,

N-tert-butyl-2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-5,6,7,8-tetrahydrophthalazin-2-yl]acetamide,

6-(2,2-difluoroethoxy)-2-[[3-[2-[3-(dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-4-oxo-5,6,7,8-tetrahydrophthalazin-1-yl]methyl]-1H-benzimidazole-5-carbonitrile,

5-(2,2-difluoroethoxy)-2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]indazole-6-carbonitrile,

5-(2,2-difluoroethoxy)-2-[[3-[2-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]indazole-6-carbonitrile,

5-(2,2-difluoroethoxy)-2-[[3-[2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]indazole-6-carbonitrile,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-cyclopentyl-acetamide,

5-(cyclopropylmethoxy)-2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]indazole-6-carbonitrile,

6-(cyclopropylmethoxy)-2-[[3-[2-(3-hydroxy-3-methyl-pyrrolidin-1-yl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]imidazo[1,2-a]pyridine-7-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-[2-[(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-[2-(3,3-difluoro-4-hydroxy-1-piperidyl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

2-[[3-[2-(4-cyclopropyl-4-hydroxy-1-piperidyl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-6-(2,2-difluoroethoxy)-3H-benzimidazole-5-carbonitrile,

2-[[3-[2-(3-cyclopropyl-3-hydroxy-pyrrolidin-1-yl)-2-oxo-ethyl], -4-oxo-phthalazin-1-yl]methyl]-6-(2,2-difluoroethoxy)-3H-benzimidazole-5-carbonitrile,

2-[[3-[2-(3-cyclopropyl-3-hydroxy-azetidin-1-yl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-6-(2,2-difluoroethoxy)-3H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-[2-[3-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

1-[[6-bromo-5-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-3-[2-[(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]-2-oxo-ethyl]cinnolin-4-one,

2-[[3-[2-[4-(cyclopropylmethyl)piperazin-1-yl]-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-6-(2,2-difluoroethoxy)-3H-benzimidazole-5-carbonitrile,

2-[[3-[2-(4-cyano-1-piperidyl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-6-(2,2-difluoroethoxy)-3H-benzimidazole-5-carbonitrile,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-methyl-N-(2-methylsulfonylethyl)acetamide,

6-(2,2-difluoroethoxy)-2-[[3-[2-(3-methylsulfonylpyrrolidin-1-yl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2-hydroxy-3,3-dimethyl-butyl)acetamide,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2,2-difluoroethyl)acetamide,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(3,3,3-trifluoropropyl)acetamide,

6-(2,2-difluoroethoxy)-2-[[3-[2-[4-(2-hydroxyethyl)piperazin-1-yl]-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

N-[cyano(cyclopropyl)methyl]-2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetamide,

6-(2,2-difluoroethoxy)-2-[[3-[2-(2,2-dimethylmorpholin-4-yl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2,2-difluoro-3-hydroxy-propyl)acetamide,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2-sulfamoylethyl)acetamide,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-(2,2,2-trifluoroethyl)acetamide,

6-(2,2-difluoroethoxy)-2-[[3-[2-(3-hydroxy-1-piperidyl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-[(3,3-difluorocyclobutyl)methyl]acetamide,

6-(2,2-difluoroethoxy)-2-[[3-[2-(3,3-dimethylpyrrolidin-1-yl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-[2-(4,4-dimethyl-1-piperidyl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

2-[[3-[2-(2,2-difluoro-5-azaspiro[2.4]heptan-5-yl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-6-(2,2-difluoroethoxy)-3H-benzimidazole-5-carbonitrile,

1-[2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetyl]-N,N-dimethyl-piperidine-4-carboxamide,

6-(2,2-difluoroethoxy)-2-[[3-[2-[3-(1-hydroxy-1-methyl-ethyl)-1-piperidyl]-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-[2-(4-morpholino-1-piperidyl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-[2-(7-oxa-2-azaspiro[3.5]nonan-2-yl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

6-(2,2-difluoroethoxy)-2-[[3-[2-(4-ethylsulfonyl-1-piperidyl)-2-oxo-ethyl]-4-oxo-phthalazin-1-yl]methyl]-3H-benzimidazole-5-carbonitrile,

2-[4-[[6-cyano-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-[2-(dimethylamino)-2-oxo-ethyl]-N-methyl-acetamide,

2-[4-[[6-chloro-5-(cyclopropylmethoxy)-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-methylsulfonyl-acetamide,

2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-methylsulfonyl-acetamide,

2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-cyclopropylsulfonyl-acetamide,

2-[4-[[6-chloro-5-(2,2-difluoroethoxy)-1H-benzimidazol-2-yl]methyl]-6-cyano-1-oxo-phthalazin-2-yl]-N-methylsulfonyl-acetamide,

N-{2-[4-(6-Chloro-5-cyclopropylmethoxy-1H-benzoimidazol-2-ylmethyl)-1-oxo-1H-phthalazin-2-yl]-propionyl}-methanesulfonamide,

2-[4-[(5-ethoxy-6-fluoro-1H-benzimidazol-2-yl)methyl]-1-oxo-phthalazin-2-yl]-N-methylsulfonyl-acetamide,

2-[4-[[5-(2,2-difluoroethoxy)-6-fluoro-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-methylsulfonyl-acetamide,

2-[4-[[6-chloro-5-[(1-cyanocyclopropyl)methoxy]-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-methylsulfonyl-acetamide,

2-[4-[[6-chloro-5-[(1-methylcyclopropyl)methoxy]-1H-benzimidazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]-N-methylsulfonyl-acetamide,

2-[4-[(6-chloro-5-ethoxy-indazol-2-yl)methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[6-chloro-5-(2,2,2-trifluoroethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[[6-chloro-5-(2,2-difluoroethoxy)indazol-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[(4-chloro-5-ethoxy-indazol-2-yl)methyl]-1-oxo-phthalazin-2-yl]acetic acid,

2-[4-[(5-chloro-6-ethoxy-indazol-2-yl)methyl]-1-oxo-phthalazin-2-yl]acetic acid,

6-(2,2-difluoroethoxy)-2-[[3-(2-morpholino-2-oxo-ethyl)-4-oxo-phthalazin-1-yl]methyl]imidazo[1,2-a]pyridine-7-carbonitrile, aid or

2-[4-[[6-chloro-5-(cyclopropylmethoxy)-1H-imidazo[4,5-b]pyridin-2-yl]methyl]-1-oxo-phthalazin-2-yl]acetic acid.

12 ) A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to claim 1 , and a pharmaceutically acceptable carrier.

13 ) A pharmaceutical composition according to claim 12 comprising a further therapeutic agent.

14 ) (canceled)

15 ) A method of prophylaxis and/or treatment of fibrotic diseases, inflammatory diseases, respiratory diseases, autoimmune diseases, metabolic diseases, cardiovascular diseases, and/or proliferative diseases comprising administering to a subject in need thereof, a compound or a pharmaceutically acceptable salt thereof according to claim 1 .

16 ) A pharmaceutical composition according to claim 13 , wherein the further therapeutic agent is an agent for the prophylaxis and/or treatment of fibrotic diseases, inflammatory diseases, respiratory diseases, autoimmune diseases, metabolic diseases, cardiovascular diseases, and/or proliferative diseases.

17 ) A method of prophylaxis and/or treatment of fibrotic diseases, inflammatory diseases, respiratory diseases, autoimmune diseases, metabolic diseases, cardiovascular diseases, and/or proliferative diseases comprising administering to a subject in need thereof, a pharmaceutical composition according to claim 12 .

Assignments (5)
RELEASE OF SECURITY INTEREST Recorded May 15, 2026
From: GILEAD SCIENCES, INC.
To: GALAPAGOS NV
Reel/Frame 075755/0189 →
SECURITY INTEREST Recorded Nov 23, 2020
From: GALAPAGOS NV
To: GILEAD SCIENCES, INC.
Reel/Frame 054503/0967 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 3, 2020
From: BREBION, FRANCK LAURENT; DUTHION, BÉRANGER
To: GALAPAGOS SASU
Reel/Frame 051412/0368 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 3, 2020
From: MAMMOLITI, OSCAR; JANSEN, KOEN KAREL; MENET, CHRISTEL JEANNE MARIE; PALISSE, ADELINE MARIE ELISE; TRICARICO, GIOVANNI ALESSANDRO; EL BKASSINY, SANDY; JAUNET, ALEXIS PATRICK CLAUDE; ALLART, BRIGITTE
To: GALAPAGOS NV
Reel/Frame 051412/0571 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 3, 2020
From: GALAPAGOS SASU
To: GALAPAGOS NV
Reel/Frame 051412/0635 →