Granted Patent B2

US 12,227,501 · App. 17/428,730 · Granted Feb 18, 2025

Inventors: Volker Schulze (Hohen Neuendorf, DE); Anne Mengel (Berlin, DE); Jens Schröder (Berlin, DE); Adelaide Clara Faria Alvares De Lemos (Berlin, DE); Wilhelm Bone (Berlin, DE); Ulf Bömer (Berlin, DE); Detlev Sülzle (Berlin, DE); Clara Christ (Berlin, DE); Roman Hillig (Berlin, DE); Christian Lechner (Berlin, DE); Steven Corsello (Boston, MA); Katarzyna Handing (Framingham, MA); Alisha Caliman (Cambridge, MA); Ulrike Rauh (Berlin, DE); Stefan Kaulfuss (Berlin, DE); Jérémie Xavier G. Mortier (Berlin, DE)

Assignees: Bayer Aktiengesellschaft; Dana-Farber Cancer Institute, Inc.; The Broad Institute, Inc.

C07D471/04A61P35/00

Abstract

Claims (287)

1. A compound of formula (I)

wherein:

R 1 represents hydrogen or a group selected from C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl-, C 1 -C 3 -alkoxy-C 1 -C 3 -alkyl-, and C 1 -C 5 -hydroxyalkyl, wherein said groups are each independently optionally substituted, one or more times, with halogen;

R 2a represents hydrogen, hydroxy, halogen, cyano, —NH 2 , —NHMe, —NMe 2 , C 1 -C 2 -alkoxy, C 1 -C 2 -haloalkyl, or C 1 -C 2 -haloalkoxy;

R 2b represents hydrogen, hydroxy, halogen, cyano, —NH 2 , —NHR 9 , or —NMe 2 ;

R 2c represents hydrogen, halogen, cyano, —NMe 2 , C 1 -C 2 -alkoxy, or C 1 -C 2 -haloalkoxy;

X represents methylene or ethylene,

wherein said methylene and ethylene groups are each independently optionally substituted, one or more times, with R 3 ;

Y represents phenyl or a heteroaryl group,

wherein said phenyl and heteroaryl groups are each independently optionally substituted, one or more times, with R 4 ;

R 3 represents hydroxy, halogen, cyano, C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkyl, C 1 -C 2 -haloalkoxy, C 3 -C 4 -cycloalkyl, —NHR 6 , R 5 O—C 1 -C 3 -alkyl, R 6 R 7 N—C 1 -C 5 -alkyl, or R 6 R 7 N—X′—C(R 10 )(R 11 )—C 1 -C 2 -alkyl-;

X′ represents methylene or ethylene;

R 4 represents hydroxy, halogen, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy, —NMe 2 , —CO 2 R 14 , —CONR 15 R 16 , or —SO 2 Me;

R 5 represents hydrogen, C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, or C 3 -C 4 -cycloalkyl;

R 6 represents hydrogen, C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, or C 3 -C 4 -cycloalkyl and

R 7 represents hydrogen, C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, C 3 -C 4 -cycloalkyl, or —CO 2 -C 1 -C 4 -alkyl, or

R 6 and R 7 , together with the nitrogen atom to which they are attached, represent a 4- to 7-membered heterocyclic ring, wherein said heterocyclic ring optionally contains one or more further heteroatoms selected from N, O, S, C(═O), S(═O), and SO 2 , and is independently optionally substituted, one or more times, with halogen, C 1 -C 3 -alkyl, C 3 -cycloalkyl-C 1 -C 2 -alkyl-, —NH 2 , —NHR 9 , —NR 9 R 9a , or hydroxy;

A represents a group selected from:

wherein * indicates the point of attachment of said group to the —NH— of formula (I);

R 8a represents hydrogen, hydroxy, halogen, cyano, C 1 -C 2 -alkyl, or C 1 -C 2 -haloalkyl;

R 8b represents hydrogen, hydroxy, halogen, cyano, C 1 -C 2 -alkyl, or C 1 -C 2 -haloalkyl;

R 8c represents hydrogen, hydroxy, halogen, cyano, C 1 -C 2 -alkyl, or C 1 -C 2 -haloalkyl;

R 8d represents hydrogen, hydroxy, halogen, cyano, C 1 -C 2 -alkyl, or C 1 -C 2 -haloalkyl;

R 8e represents hydrogen, hydroxy, halogen, cyano, C 1 -C 2 -alkyl, or C 1 -C 2 -haloalkyl;

R 8f represents hydrogen, hydroxy, halogen, cyano, C 1 -C 2 -alkyl, or C 1 -C 2 -haloalkyl;

R 8g represents hydrogen or halogen;

R 9 represents C 1 -C 3 -alkyl or cyclopropyl;

R 9a represents C 1 -C 3 -alkyl or cyclopropyl;

R 10 represents methyl, halogen, or hydroxy;

R 11 represents methyl, halogen, or hydroxy;

R 13a represents hydrogen, or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 3 -C 4 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl-, and C 1 -C 3 -alkoxy-C 1 -C 3 -alkyl-, wherein said groups are each independently optionally substituted, one or more times, with halogen and

R 13b represents hydrogen, or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl-, and C 1 -C 3 -alkoxy-C 1 -C 3 -alkyl-, wherein said groups are each independently optionally substituted, one or more times, with halogen, or,

R 13a and R 13b , together with the carbon atom to which they are attached, form a C 3 -C 5 -cycloalkyl ring or a 4- to 5-membered heterocyclic ring;

R 14 represents hydrogen, methyl, or ethyl; and

R 15 represents hydrogen, methyl, or ethyl and

R 16 represents hydrogen, methyl, ethyl, methoxyethyl, or dimethylaminoethyl, or

R 15 and R 16 , together with the nitrogen atom to which they are attached, represent a 5- to 6-membered heterocyclic ring, wherein said heterocyclic ring optionally contains one or two further heteroatoms selected from N, O, S, C(═O), S(═O), and SO 2 ;

or an N-oxide, a salt, a tautomer, or a stereoisomer of said compound, or a salt of said N-oxide, tautomer, or stereoisomer.

2. The compound of formula (I) according to claim 1 , wherein:

R 1 represents hydrogen or a group selected from C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl-, and C 1 -C 5 -hydroxyalkyl, wherein said groups are each independently optionally substituted, one or more times with halogen;

R 2a represents hydrogen or halogen;

R 2b represents hydrogen, halogen, —NH 2 , or —NHR 9 ;

R 2 c represents hydrogen or halogen;

X represents methylene, wherein said methylene group is independently optionally substituted, one or more times, with R 3 ;

Y represents phenyl or a pyridyl group,

wherein said phenyl and pyridyl groups are each independently optionally substituted, one or more times, with R 4 ;

R 3 represents hydroxy, C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, —NHR 6 , R 5 O—C 1 -C 3 -alkyl, or R 6 R 7 N—C 1 -C 5 -alkyl;

R 4 represents halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, methoxy, —OCF 3 , —NMe 2 , —CO 2 R 14 , —CONR 15 R 16 , or —SO 2 Me;

R 5 represents hydrogen, methyl, or trifluoromethyl;

R 6 represents hydrogen, C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, or C 3 -C 4 -cycloalkyl and

R 7 represents hydrogen, C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, C 3 -C 4 -cycloalkyl, or —CO 2 -tert-butyl, or

R 6 and R 7 , together with the nitrogen atom to which they are attached, represent a 4- to 7-membered heterocyclic ring, wherein said heterocyclic ring optionally contains one or more further heteroatoms selected from N, O, and S, or a group C(═O), and is independently optionally substituted, one or more times, with halogen, C 1 -C 3 -alkyl, C 3 -cycloalkyl-C 1 -C 2 -alkyl-, —NH 2 , —NHR 9 , or —NR 9 R 9a ;

A represents a group selected from:

wherein * indicates the point of attachment of said group to the —NH— of formula (I);

R 8a represents hydrogen, hydroxy, halogen, or C 1 -C 2 -alkyl;

R 8b represents hydrogen, hydroxy, halogen, or C 1 -C 2 -alkyl;

R 8c represents hydrogen, hydroxy, halogen, or C 1 -C 2 -alkyl;

R 8d represents hydrogen, hydroxy, halogen, or C 1 -C 2 -alkyl;

R 8e represents hydrogen, hydroxy, halogen, or C 1 -C 2 -alkyl;

R 8f represents hydrogen, hydroxy, halogen, or C 1 -C 2 -alkyl;

R 8g represents hydrogen or halogen;

R 9 represents C 1 -C 3 -alkyl or cyclopropyl;

R 9a represents C 1 -C 3 -alkyl or cyclopropyl;

R 13a represents hydrogen or C 1 -C 2 -alkyl, wherein said C 1 -C 2 -alkyl is independently optionally substituted, one or more times, with halogen and

R 13b represents hydrogen or C 1 -C 2 -alkyl, wherein said C 1 -C 2 -alkyl is independently optionally substituted, one or more times, with halogen, or

R 13a and R 13b , together with the carbon atom to which they are attached, form a C 3 -C 5 -cycloalkyl ring;

R 14 represents hydrogen, methyl or ethyl; and

R 15 represents hydrogen or methyl and

R 16 represents methyl, ethyl, methoxyethyl, or dimethylaminoethyl, or

R 15 and R 16 , together with the nitrogen atom to which they are attached, represent a 5- to 6-membered heterocyclic ring, wherein said heterocyclic ring optionally contains one or two further heteroatoms selected from N, O, and S;

or an N-oxide, a salt, a tautomer, or a stereoisomer of said compound, or a salt of said N-oxide, tautomer, or stereoisomer.

3. The compound of formula (I) according to claim 1 , wherein:

R 1 represents hydrogen or a group selected from C 1 -C 2 -alkyl, cyclopropyl, and cyclopropylmethyl, wherein said C 1 -C 2 -alkyl is independently optionally substituted, one or more times, with halogen;

R 2a represents hydrogen;

R 2b represents hydrogen;

R 2c represents hydrogen;

X represents methylene, wherein said methylene group is independently optionally substituted, one or two times, with R 3 ;

Y represents phenyl, wherein said phenyl is independently optionally substituted, one or two times, with R 4 ;

R 3 represents C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, R 5 O—C 1 -C 3 -alkyl, or R 6 R 7 N—C 1 -C 3 -alkyl;

R 4 represents halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, —NMe 2 , —CO 2 R 14 , —CONR 15 R 16 , or —SO 2 Me;

R 5 represents hydrogen;

R 6 represents hydrogen or C 1 -C 2 -alkyl and

R 7 represents hydrogen, C 1 -C 2 -alkyl, or —CO 2 -tert-butyl, or

R 6 and R 7 , together with the nitrogen atom to which they are attached, represent a 4- to 6-membered heterocyclic ring, wherein said heterocyclic ring optionally contains further heteroatoms selected from N, O, and S, and is independently optionally substituted, one or more times, with halogen, C 1 -C 3 -alkyl, —NH 2 , —NHR 9 , or —NR 9 R 9a ,

A represents a group selected from:

wherein * indicates the point of attachment of said group to the —NH— of formula (I);

R 8a represents hydrogen, hydroxy, halogen, or C 1 -C 2 -alkyl;

R 8b represents hydrogen, hydroxy, halogen, or C 1 -C 2 -alkyl;

R 8c represents hydrogen, hydroxy, halogen, or C 1 -C 2 -alkyl;

R 8f represents hydrogen or halogen;

R 8g represents hydrogen or halogen;

R 9 represents C 1 -C 3 -alkyl;

R 9a represents C 1 -C 3 -alkyl;

R 13a represents hydrogen or methyl, wherein said methyl is independently optionally substituted, one or more times, with halogen and

R 13b represents hydrogen or methyl, wherein said methyl is independently optionally substituted, one or more times, with halogen, or

R 13a and R 13b , together with the carbon atom to which they are attached, form a C 3 -C 4 -cycloalkyl ring;

R 14 represents methyl; and

R 15 represents hydrogen and

R 16 represents methoxyethyl or dimethylaminoethyl, or

R 15 and R 16 , together with the nitrogen atom to which they are attached, represent a 6-membered heterocyclic ring, wherein said heterocyclic ring optionally contains one or two further heteroatoms selected from N and O;

or an N-oxide, a salt, a tautomer, or a stereoisomer of said compound, or a salt of said N-oxide, tautomer, or stereoisomer.

4. The compound of formula (I) according to claim 1 , which is selected from:

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-phenylacetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluoro-3-methylphenyl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propanamide,

(2S)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propanamide,

(2R)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propanamide,

N-[4-(3-anilino-5-cyclopropyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-y1]-2-(4-fluorophenyl)acetamide,

(N-[4-(3-anilino-5-cyclopropyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propanamide,

N-[4-(3-anilino-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propanamide,

(2S)-N-[4-(3-anilino-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propanamide,

(2R)-N-[4-(3-anilino-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propanamide,

2-(4-fluorophenyl)-N-(4-{5-methyl-4-oxo-3-[(pyridin-2-yl)amino]-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl}pyridin-2-yl)acetamide,

N-{4-[3-(2-chloroanilino)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-{4-[3-(2-chloroanilino)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propanamide,

(2R)-N-{4-[3-(2-chloroanilino)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propanamide,

(2S)-N-{4-[3-(2-chloroanilino)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propanamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)-3-hydroxypropanamide,

(2R)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)-3-hydroxypropanamide,

(2S)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)-3-hydroxypropanamide,

N-{4-[3-anilino-5-(cyclopropylmethyl)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-[4-(3-anilino-5-ethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propanamide,

N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-y1]-2-(4-fluorophenyl)acetamide,

N-{4-[3-anilino-5-(2-hydroxy-2-methylpropyl)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-{4-[3-anilino-5-(2-hydroxy-2-methylpropyl)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propanamide,

(2R)-N-[4-(3-anilino-5-ethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-y1]-2-(4-fluorophenyl)propanamide,

(2S)-N-[4-(3-anilino-5-ethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-y1]-2-(4-fluorophenyl)propanamide,

N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propanamide,

N-[4-(3-anilino-5-ethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)acetamide,

N-{4-[3-(2-fluoroanilino)-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propanamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4-(morpholin-4-yl)-2-phenylbutanamide,

(2R)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4-(morpholin-4-yl)-2-phenylbutanamide,

(2S)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4-(morpholin-4-yl)-2-phenylbutanamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4,4-difluoro-2-phenylbutanamide,

(2R)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4,4-difluoro-2-phenylbutanamide,

(2S)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4,4-difluoro-2-phenylbutanamide,

N-{4-[3-anilino-4-oxo-5-(2,2,2-trifluoroethyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-{4-[3-anilino-4-oxo-5-(2,2,2-trifluoroethyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propanamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4-(dimethylamino)-2-phenylbutanamide,

(2R)-N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propenamide,

(2S)-N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propenamide,

(2R)-N-{4-[3-(2-fluoroanilino)-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propenamide,

(2S)-N-{4-[3-(2-fluoroanilino)-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propenamide,

N-{4-[3-anilino-4-oxo-6-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-[4-(3-anilino-5,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)acetamide,

4,4-difluoro-N-{4-[3-(2-fluoroanilino)-5,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide,

(2R)-4,4-difluoro-N-{4-[3-(2-fluoroanilino)-5,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide,

(2S)-4,4-difluoro-N-{4-[3-(2-fluoroanilino)-5,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide,

N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-y1]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2S)-N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2R)-N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(pyridin-4-yl)acetamide,

N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(pyridin-3-yl)acetamide,

N-{4-[3-anilino-5-(2-methoxyethyl)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-[4-(3′-anilino-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2S)-N-[4-(3′-anilino-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(−)-N-[4-(3′-anilino-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide (Enantiomer 2),

N-[4-(3′-anilino-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-2-(4-fluorophenyl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-5-(dimethylamino)-2-phenylpentanamide,

(2R)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-5-(dimethylamino)-2-phenylpentanamide,

(2S)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-5-(dimethylamino)-2-phenylpentanamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2R)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2S)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(pyridin-4-yl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-[4-(methanesulfonyl)phenyl]acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-[4-(trifluoromethyl)phenyl]acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(pyridin-3-yl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-methylphenyl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-[3-(methanesulfonyl)phenyl]acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(3-methylphenyl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(2-methylphenyl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(pyridin-4-yl)propenamide,

(2S)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(pyridin-4-yl)propenamide,

(2R)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(pyridin-4-yl)propenamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)butanamide,

(2R)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)butanamide,

(2S)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)butanamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-[4-(difluoromethyl)phenyl]acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-chlorophenyl)propenamide,

(2R)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-chlorophenyl)propenamide,

(2S)-N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-chlorophenyl)propenamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(2,4-difluorophenyl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(3,4-difluorophenyl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-[4-(dimethylamino)phenyl]acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(2-methylpyridin-4-yl)acetamide,

N-{4-[3-(2-fluoroanilino)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-{4-[3-(2-chloro-3-fluoroanilino)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-{4-[3-anilino-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-y1}-2-(4-fluorophenyl)acetamide,

N-{4-[(6R)-3-anilino-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-{4-[(6S)-3-anilino-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

(2RS)-N-{4-[(6S)-3-anilino-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propenamide,

(2R)-N-{4-[(6S)-3-anilino-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propenamide,

(2S)-N-{4-[(6S)-3-anilino-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propenamide,

(2RS)-N-{4-[(6R)-3-anilino-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propenamide,

(2R)-N-{4-[(6R)-3-anilino-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propenamide,

(2S)-N-{4-[(6R)-3-anilino-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propenamide,

N-{4-[3-anilino-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-y1}-2-(pyridin-4-yl)acetamide,

N-{4-[(6R)-3-anilino-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(pyridin-4-yl)acetamide,

N-{4-[(6S)-3-anilino-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(pyridin-4-yl)acetamide,

N-{4-[3-(2-fluoroanilino)-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-{4-[(6R)-3-(2-fluoroanilino)-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-{4-[(6S)-3-(2-fluoroanilino)-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

(2RS)-4,4-difluoro-N-{4-[(6R)-3-(2-fluoroanilino)-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide,

(2S)-4,4-difluoro-N-{4-[(6R)-3-(2-fluoroanilino)-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide,

(2R)-4,4-difluoro-N-{4-[(6R)-3-(2-fluoroanilino)-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide,

(2RS)-4,4-difluoro-N-{4-[(6S)-3-(2-fluoroanilino)-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide,

(2S)-4,4-difluoro-N-{4-[(6S)-3-(2-fluoroanilino)-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide,

(2R)-4,4-difluoro-N-{4-[(6S)-3-(2-fluoroanilino)-5,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide,

N-{4-[3-(2-chloro-3-fluoroanilino)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2R)-N-{4-[3-(2-chloro-3-fluoroanilino)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2S)-N-{4-[3-(2-chloro-3-fluoroanilino)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide,

N-{4-[3-(2-chloro-3-fluoroanilino)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-{4-[6,6-dimethyl-3-(2-methylanilino)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(pyrazin-2-yl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(pyridin-2-yl)acetamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-[3-(trifluoromethyl)phenyl]acetamide,

methyl 4-(2-{[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]amino}-2-oxoethyl)benzoate,

N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-4,4-difluoro-2-[4-(methanesulfonyl)phenyl]butanamide,

N-{4-[3-(3-fluoroanilino)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

(2S)-4,4-difluoro-N-{4-[3-(3-fluoroanilino)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide,

(2R)-4,4-difluoro-N-{4-[3-(3-fluoroanilino)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide,

N-{4-[3′-(2-chloro-3-fluoroanilino)-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-{4-[3′-(2-chloro-3-fluoroanilino)-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2R)-N-{4-[3′-(2-chloro-3-fluoroanilino)-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2S)-N-{4-[3′-(2-chloro-3-fluoroanilino)-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide,

2-(4-fluorophenyl)-N-(4-{3-[(6-fluoropyridin-2-yl)amino]-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl}pyridin-2-yl)acetamide,

2-(4-fluorophenyl)-N-(4-{3-[(6-fluoropyridin-2-yl)amino]-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl}pyridin-2-yl)acetamide-1,1′,1″-phosphoryltripyrrolidine complex,

4,4-difluoro-2-(4-fluorophenyl)-N-(4-{3-[(6-fluoropyridin-2-yl)amino]-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl}pyridin-2-yl)butanamide,

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-(4-{3-[(6-fluoropyridin-2-yl)amino]-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl}pyridin-2-yl)butanamide,

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-(4-{3-[(6-fluoropyridin-2-yl)amino]-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl}pyridin-2-yl)butanamide,

N-{4-[3-(3-fluoro-2-methylanilino)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

N-{4-[6,6-dimethyl-3-(2-methylanilino)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propenamide,

(2R)-N-{4-[6,6-dimethyl-3-(2-methylanilino)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propenamide,

(2S)-N-{4-[6,6-dimethyl-3-(2-methylanilino)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)propenamide,

N-{4-[6,6-dimethyl-3-(2-methylanilino)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2R)-N-{4-[6,6-dimethyl-3-(2-methylanilino)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2S)-N-{4-[6,6-dimethyl-3-(2-methylanilino)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide,

tert-butyl [3-{[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]amino}-2-(4-fluorophenyl)-3-oxopropyl]carbamate,

3-amino-N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propanamide-hydrogen chloride salt,

(2R)-3-amino-N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propenamide,

(2S)-3-amino-N-[4-(3-anilino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(4-fluorophenyl)propenamide,

2-(4-fluorophenyl)-N-{4-[3′-(2-methylanilino)-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl]pyridin-2-yl}acetamide,

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3′-(2-methylanilino)-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl]pyridin-2-yl}butanamide,

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3′-(2-methylanilino)-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl]pyridin-2-yl}butanamide,

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3′-(2-methylanilino)-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl]pyridin-2-yl}butanamide,

N-[4-(3′-anilino-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclopropane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-2-(4-fluorophenyl)acetamide,

N-[4-(3′-anilino-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclopropane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2R)-N-[4-(3′-anilino-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclopropane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2S)-N-[4-(3′-anilino-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclopropane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

N-{4-[3-(2,5-difluoroanilino)-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide,

4-(2-{[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]amino}-2-oxoethyl)benzoic acid,

4-(2-{[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]amino}-2-oxoethyl)-N-(2-methoxyethyl)benzamide,

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-[4-(piperazine-1-carbonyl)phenyl]acetamide,

N-{4-[3-(2,3-difluoroanilino)-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)acetamide formamide salt,

4-(2-{[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]amino}-2-oxoethyl)-N-[2-(dimethylamino)ethyl]benzamide,

N-[4-(3′-anilino-5′-methyl-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-2-(4-fluorophenyl)acetamide,

N-[4-(3′-anilino-5′-methyl-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-2-(4-fluorophenyl)propenamide,

(2R)-N-[4-(3′-anilino-5′-methyl-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-2-(4-fluorophenyl)propenamide,

(2S)-N-[4-(3′-anilino-5′-methyl-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-2-(4-fluorophenyl)propenamide,

N-[4-(3′-anilino-5′-methyl-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2R)-N-[4-(3′-anilino-5′-methyl-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

(2S)-N-[4-(3′-anilino-5′-methyl-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclobutane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide,

N-[4-(3′-anilino-5′-methyl-4′-oxo-1′,4′,5′,7′-tetrahydrospiro [cyclopropane-1,6′-pyrrolo[3,2-c]pyridin]-2′-yl)pyridin-2-yl]-4,4-difluoro-2-(4-fluorophenyl)butanamide, and

N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-(2,4,6-trifluorophenyl)acetamide;

or an N-oxide, a salt, a tautomer, or a stereoisomer of said compound, or a salt of said N-oxide, tautomer, or stereoisomer.

5. A method of preparing a compound of general formula (I) according to claim 1 , said method comprising reacting an intermediate compound of general formula (1-3), or a salt thereof:

wherein R 1 , R 2 ª, R 2b , R 2c , R 13a , R 13b , and A are as defined for the compound of general formula (I) according to claim 1 ,

with an acylating reagent selected from:

a) a carboxylic acid of formula

b) an acyl halide of formula

wherein Hal represents F, C 1 , or Br, and

c) an anhydride of formula

wherein X and Y are as defined for the compound of general formula (I) according to claim 1 , to give a compound of general formula (I), or a salt thereof:

wherein R 1 , R 2a , R 2b , R 2c , R 13a , R 13b , A, X, and Y are as defined for the compound of general formula (I) according to claim 1 .

6. A method of treating a hyperproliferative disease selected from lymphoma, lung cancer, a colon tumor, and metastases thereof in a subject, comprising administering a compound according to claim 1 to the subject.

7. The method according to claim 6 , wherein the hyperproliferative disease is selected from a lymphoma and metastases thereof.

8. The method according to claim 7 , wherein the lymphoma is selected from diffuse large B-cell lymphoma and metastases thereof.

9. The method according to claim 6 , wherein the hyperproliferative disease is selected from a lung tumour, a colon tumour, and metastases thereof.

10. The method according to claim 9 , wherein the lung tumour is selected from a lung carcinoma and metastases thereof.

11. The method according to claim 9 , wherein the colon tumour is selected from a colorectal carcinoma and metastases thereof.

12. A pharmaceutical composition comprising at least one compound of general formula (I) according to claim 1 , together with at least one pharmaceutically acceptable auxiliary.

13. A method of treating a hyperproliferative disease selected from lymphoma, lung cancer, a colon tumor and metastases thereof in a subject, comprising administering a composition according to claim 12 .

14. A combination comprising one or more first active ingredients selected from a compound of general formula (I) according to claim 1 , and one or more second active ingredients selected from chemotherapeutic anti-cancer agents and target-specific anti-cancer agents.

15. An intermediate compound of general formula (1-3), or a salt thereof:

wherein R 1 , R 2a , R 2b , R 2c , R 13a , R 13b , and A are as defined for the compound of general formula (I) according to claim 1 , with the proviso that R 1 is not hydrogen or methyl.

Assignments (3)

Continuity (2)

References Cited (43)

Cited By (2)

US 12,565,496 US 12,692,261