IP Library › Granted Patent US 12692261

Granted Patent B2

US 12692261 · App. 18/018,216 · Granted Jul 28, 2026

Substituted heterocyclic compounds and therapeutic uses thereof

Inventors: Volker Schulze (Hohen Neuendorf, DE); Anne Mengel (Berlin, DE); Clara Adelaide Faria Alvares De Lemos (Berlin, DE); Sven Christian (East Boston, MA); Ulf Bömer (Glienicke, DE); Roman Hillig (Berlin, DE); Christian Lechner (Berlin, DE); Jérémie Xavier Mortier (Berlin, DE); Stefan Kaulfuss (Berlin, DE); Steven Corsello (Boston, MA); Katarzyna Handing (Framingham, MA); Amael Madec (Boston, MA); Laura Furst (Somerville, MA); Mrinal Shekhar (Quincy, MA); Markus Berger (Berlin, DE); Rajesha Rupaimoole (North Billerica, MA); Philip Lienau (Berlin, DE); Douglas Orsi (Watertown, MA); David McKinney (Cambridge, MA); Krzysztof Brzezinka (Berlin, DE)

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

C07D471/04 A61P35/00 C07D401/06 C07D401/14 C07D405/14 C07D487/04 C07F7/0812

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Quick Facts

Patent No.: US 12692261
App. No.: 18/018,216
Granted: Jul 28, 2026
Kind: B2

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Abstract

Compounds of formula (I), process for their production and their use as pharmaceuticals.

Claims (230)

1 . A compound of formula (I)

wherein:

A represents a group selected from:

X represents N, C—H, C—F, C—Cl, or C-Me;

Y represents N, or C—R 4a ;

Z represents N, or C—R 4b ,

wherein none or one of X, Y, and Z represent N;

R 1b represents hydrogen or halogen;

R 1c represents hydrogen or fluoro;

R 1e represents hydrogen or fluoro;

R 1f represents hydrogen or fluoro;

R 1g represents hydrogen or fluoro;

R 2 represents C 1 -C 3 -haloalkyl, or C 1 -C 3 -hydroxyalkyl;

R 3 represents phenyl, wherein said phenyl is independently optionally substituted, one or more times, with halogen, methyl, methoxy, C 1 -C 2 -haloalkyl, or C 1 -C 2 -haloalkoxy;

R 4a represents hydrogen, halogen, C 1 -C 3 -alkyl, C 2 -alkenyl, methoxy, difluoromethoxy, C 3 -cycloalkyl, 4-membered heterocycloalkyl, cyclopropyloxy, 4-membered heterocycloalkyl-O— or R 5a R 6a N—;

R 4b represents hydrogen, halogen, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 1 -C 3 -haloalkyl-CH 2 —, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, C 3 -C 5 -cycloalkyl, C 3 -C 5 -cycloalkyl-C 1 -C 2 -alkyl, C 3 -C 5 -cycloalkyl-O—, C 3 -C 5 -cycloalkyl-CH 2 —O—, piperazin-1-yl, morpholin-4-yl, 3- to 6-membered heterocycloalkyl connected via a carbon atom thereof, pyrrolidin-2-one, piperidin-2-one, morpholin-3-one, 4-methylpiperazin-2-one, 3- to 6-membered heterocycloalkyl-O—, 3- to 6-membered heterocycloalkyl-CH 2 —O—, C 1 -C 3 -alkoxy-C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-C 2 -C 3 -alkoxy-, C 1 -C 4 -hydroxyalkyl, or C 1 -C 4 -hydroxyalkyl-O—;

wherein said C 3 -C 5 -cycloalkyl, C 3 -C 5 -cycloalkyl-C 1 -C 2 -alkyl, C 3 -C 5 -cycloalkyl-O—, C 3 -C 5 -cycloalkyl-CH 2 —O—, 3- to 6-membered heterocycloalkyl, pyrrolidin-2-one, piperidin-2-one, morpholin-3-one, 4-methylpiperazin-2-one, 3- to 6-membered heterocycloalkyl-O—, 3- to 6-membered heterocycloalkyl-CH 2 —O—, piperazin-1-yl, morpholin-4-yl, C 1 -C 3 -alkoxy-C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-C 2 -C 3 -alkoxy-, C 1 -C 4 -hydroxyalkyl, and C 1 -C 4 -hydroxyalkyl-O-groups are optionally substituted, one, two or three times, with halogen, methyl, or methoxy;

R 5a represents hydrogen or methyl;

R 6a represents hydrogen or methyl, or

R 5a and R 6a , together with the nitrogen atom to which they are attached, represent a 4-membered heterocyclic ring, wherein said heterocyclic ring is optionally substituted with methyl;

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:

A represents a group selected from:

X represents N, C—H, C—F or C—Cl;

Y represents N or C—R 4a ;

Z represents N, or C—R 4b ,

wherein none or one of X, Y, and Z represent N;

R 1b represents hydrogen or fluoro;

R 1c represents hydrogen;

R 1e represents hydrogen;

R 1f represents hydrogen or fluoro;

R 1g represents hydrogen or fluoro;

R 2 represents C 1 -C 3 -haloalkyl, or C 1 -C 3 -hydroxyalkyl;

R 3 represents phenyl, wherein said phenyl is independently optionally substituted, one or more times, with halogen, methyl or C 1 -haloalkyl;

R 4a represents hydrogen, halogen, C 1 -alkyl, C 2 -alkenyl, C 3 -cycloalkyl, 4-membered heterocycloalkyl, or R 5a R 6a N—;

R 4b represents hydrogen, halogen, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 1 -C 3 -haloalkyl-CH 2 —, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, C 3 -C 4 -cycloalkyl, C 3 -C 4 -cycloalkyl-C 1 -C 2 -alkyl, C 3 -C 4 -cycloalkyl-O—, C 3 -C 4 -cycloalkyl-CH 2 —O—, piperazin-1-yl, morpholin-4-yl, 3- to 6-membered heterocycloalkyl connected via a carbon atom thereof, pyrrolidin-2-one, piperidin-2-one, morpholin-3-one, 4-methylpiperazin-2-one, 3- to 6-membered heterocycloalkyl-O—, 3- to 6-membered heterocycloalkyl-CH 2 —O—, C 1 -C 3 -alkoxy-C 2 -C 3 -alkoxy-, C 1 -C 4 -hydroxyalkyl, or C 1 -C 4 -hydroxyalkyl-O—,

wherein said C 3 -C 4 -cycloalkyl, C 3 -C 4 -cycloalkyl-C 1 -C 2 -alkyl, C 3 -C 4 -cycloalkyl-O—, C 3 -C 4 -cycloalkyl-CH 2 —O—, 3- to 6-membered heterocycloalkyl, pyrrolidin-2-one, piperidin-2-one, morpholin-3-one, 4-methylpiperazin-2-one, 3- to 6-membered heterocycloalkyl-O—, 3- to 6-membered heterocycloalkyl-CH 2 —O—, piperazin-1-yl, morpholin-4-yl, C 1 -C 3 -alkoxy-C 2 -C 3 -alkoxy-, C 1 -C 4 -hydroxyalkyl and C 1 -C 4 -hydroxyalkyl-O-groups are optionally substituted, one or two times, with halogen or methyl;

R 5a represents hydrogen or methyl;

R 6a represents hydrogen or methyl, or

R 5a and R 6a , together with the nitrogen atom to which they are attached, represent a 4-membered heterocyclic ring;

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 2 , wherein:

A represents:

X represents C—H, C—F;

Y represents N or C—R 4a ;

Z represents N or C—R 4b ;

wherein none or one of Y and Z represent N;

R 1b represents hydrogen or fluoro;

R 1e represents hydrogen;

R 1f represents hydrogen;

R 1g represents hydrogen or fluoro;

R 2 represents C 1 -C 2 -haloalkyl;

R 3 represents phenyl, wherein said phenyl is independently optionally substituted, one or more times, with halogen or methyl;

R 4a represents hydrogen, halogen, or methyl;

R 4b represents hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 3 -haloalkyl-CH 2 —, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, C 3 -cycloalkyl, C 3 -cycloalkyl-C 1 -C 2 -alkyl, C 3 -cycloalkyl-O—, C 3 -cycloalkyl-CH 2 —O—, piperazin-1-yl, morpholin-4-yl, 3- to 6-membered heterocycloalkyl connected via a carbon atom thereof, pyrrolidin-2-one, piperidin-2-one, morpholin-3-one, 4-methylpiperazin-2-one, 3- to 6-membered heterocycloalkyl-O— or 3- to 6-membered heterocycloalkyl-CH 2 —O—, C 1 -C 3 -alkoxy-C 2 -C 3 -alkoxy-, C 1 -C 4 -hydroxyalkyl, or C 1 -C 4 -hydroxyalkyl-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 . A compound of formula (I) according to claim 1 , which is a compound of formula (XXIII)

wherein:

X represents C—H, or C—F;

Y represents N or C—R 4a ;

Z represents N or C—R 4b ;

wherein none or one of Y and Z represent N;

R 1b represents hydrogen or fluoro;

R 1e represents hydrogen;

R 1f represents hydrogen;

R 1g represents hydrogen or fluoro;

R 4a represents hydrogen, halogen, or methyl;

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

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[5-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[5-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[5-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[6-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[6-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[6-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[6-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[6-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[6-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-[4-(6-fluoro-3-phenyl-1H-pyrrolo[3,2-b]pyridin-2-yl)pyridin-2-yl]butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-[4-(6-fluoro-3-phenyl-1H-pyrrolo[3,2-b]pyridin-2-yl)pyridin-2-yl]butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-[4-(6-fluoro-3-phenyl-1H-pyrrolo[3,2-b]pyridin-2-yl)pyridin-2-yl]butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-[4-(3-phenyl-1H-pyrrolo[3,2-b]pyridin-2-yl)pyridin-2-yl]butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-[4-(3-phenyl-1H-pyrrolo[3,2-b]pyridin-2-yl)pyridin-2-yl]butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-[4-(3-phenyl-1H-pyrrolo[3,2-b]pyridin-2-yl)pyridin-2-yl]butanamide; and

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-(6-fluoropyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-(6-fluoropyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-(6-fluoropyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

N-{4-[7-(2,2-difluoroethoxy)-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2R)—N-{4-[7-(2,2-difluoroethoxy)-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2S)—N-{4-[7-(2,2-difluoroethoxy)-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

4,4-difluoro-N-{4-[5-fluoro-6-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2R)-4,4-difluoro-N-{4-[5-fluoro-6-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2S)-4,4-difluoro-N-{4-[5-fluoro-6-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

4,4-difluoro-N-{4-[5-fluoro-7-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2R)-4,4-difluoro-N-{4-[5-fluoro-7-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2S)-4,4-difluoro-N-{4-[5-fluoro-7-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

4,4-difluoro-N-{4-[5-fluoro-7-methoxy-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2R)-4,4-difluoro-N-{4-[5-fluoro-7-methoxy-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2S)-4,4-difluoro-N-{4-[5-fluoro-7-methoxy-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

N-{4-[7-(cyclopropyloxy)-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2R)—N-{4-[7-(cyclopropyloxy)-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2S)—N-{4-[7-(cyclopropyloxy)-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

N-{4-[7-(cyclopropylmethyl)-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2R)—N-{4-[7-(cyclopropylmethyl)-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2S)—N-{4-[7-(cyclopropylmethyl)-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

N-{4-[7-chloro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

N-{4-[7-{[(2R)-1,4-dioxan-2-yl]methoxy}-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2R)—N-{4-[7-{[(2R)-1,4-dioxan-2-yl]methoxy}-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2S)—N-{4-[7-{[(2R)-1,4-dioxan-2-yl]methoxy}-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

4,4-difluoro-N-{4-[5-fluoro-7-{[(3S)-oxolan-3-yl]oxy}-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2R)-4,4-difluoro-N-{4-[5-fluoro-7-{[(3S)-oxolan-3-yl]oxy}-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2S)-4,4-difluoro-N-{4-[5-fluoro-7-{[(3S)-oxolan-3-yl]oxy}-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

4,4-difluoro-N-{4-[5-fluoro-7-(4-methylpiperazin-1-yl)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

N-(4-{7-[(2S)-1,4-dioxan-2-ylmethoxy]-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl}pyridin-2-yl)-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2R)—N-{4-[7-{[(2S)-1,4-dioxan-2-yl]methoxy}-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2S)—N-{4-[7-{[(2S)-1,4-dioxan-2-yl]methoxy}-5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-fluoro-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

4,4-difluoro-N-{4-[5-fluoro-7-{[oxolan-2-yl]methoxy}-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[2-fluoro-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[2-fluoro-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[2-fluoro-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-5H-pyrrolo[3,2-c]pyridazin-6-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-5H-pyrrolo[3,2-c]pyridazin-6-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-5H-pyrrolo[3,2-c]pyridazin-6-yl]pyridin-2-yl}butanamide;

N-{4-[3-chloro-7-(pyridin-2-yl)-5H-pyrrolo[3,2-c]pyridazin-6-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

4,4-difluoro-N-{4-[5-fluoro-7-(morpholin-4-yl)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

N-{4-[5-chloro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

N-(4-(6-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)pyridin-2-yl)-2-(4-fluorophenyl)-3-hydroxypropanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[4-{[(3S)-oxolan-3-yl]oxy}-7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[4-{[(3S)-oxolan-3-yl]oxy}-7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[4-{[(3S)-oxolan-3-yl]oxy}-7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

N-{4-[7-(2,2-difluoroethoxy)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2R)—N-{4-[7-(2,2-difluoroethoxy)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2S)—N-{4-[7-(2,2-difluoroethoxy)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

N-{4-[4-(2,2-difluoroethoxy)-7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2R)—N-{4-[4-(2,2-difluoroethoxy)-7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2S)—N-{4-[4-(2,2-difluoroethoxy)-7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[6-methoxy-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[6-methoxy-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[6-methoxy-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-methyl-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-methyl-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-methyl-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-methyl-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

N-{4-[6-chloro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2R)—N-{4-[6-chloro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2S)—N-{4-[6-chloro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

4,4-difluoro-N-{4-[5-fluoro-7-(2-methoxyethoxy)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2R)-4,4-difluoro-N-{4-[5-fluoro-7-(2-methoxyethoxy)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2S)-4,4-difluoro-N-{4-[5-fluoro-7-(2-methoxyethoxy)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(piperazin-1-yl)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(piperazin-1-yl)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(piperazin-1-yl)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}butanamide;

4,4-difluoro-N-{4-[5-fluoro-3-(4-fluoropyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2R)-4,4-difluoro-N-{4-[5-fluoro-3-(4-fluoropyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2S)-4,4-difluoro-N-{4-[5-fluoro-3-(4-fluoropyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

4,4-difluoro-N-{4-[5-fluoro-7-(2-hydroxypropan-2-yl)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2R)-4,4-difluoro-N-{4-[5-fluoro-7-(2-hydroxypropan-2-yl)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2S)-4,4-difluoro-N-{4-[5-fluoro-7-(2-hydroxypropan-2-yl)-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-methoxy-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-methoxy-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[3-methoxy-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

2-(4-fluorophenyl)-4-hydroxy-N-(4-(3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl)pyridin-2-yl)-butanamide;

N-{4-[3-(difluoromethoxy)-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2S)—N-{4-[3-(difluoromethoxy)-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2R)—N-{4-[3-(difluoromethoxy)-7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

4,4-difluoro-N-{4-[5-fluoro-3-(5-fluoropyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2R)-4,4-difluoro-N-{4-[5-fluoro-3-(5-fluoropyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

(2S)-4,4-difluoro-N-{4-[5-fluoro-3-(5-fluoropyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}-2-(4-fluorophenyl)butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-[4-(3-pyrimidin-2-yl-1H-pyrrolo[3,2-b]pyridin-2-yl)-2-pyridyl]butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[4-methoxy-7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-(4-{5-fluoro-3-(pyridin-2-yl)-7-[tetrahydrofuran-2-yl]-1H-pyrrolo[3,2-b]pyridin-2-yl}pyridin-2-yl) butanamide;

(2R)-4,4-difluoro-N-(4-{5-fluoro-7-[(2R)-oxolan-2-yl]-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl}pyridin-2-yl)-2-(4-fluorophenyl)butanamide;

(2R)-4,4-difluoro-N-(4-{5-fluoro-7-[(2S)-oxolan-2-yl]-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl}pyridin-2-yl)-2-(4-fluorophenyl)butanamide;

(2S)-4,4-difluoro-N-(4-{5-fluoro-7-[(2R)-oxolan-2-yl]-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl}pyridin-2-yl)-2-(4-fluorophenyl)butanamide;

(2S)-4,4-difluoro-N-(4-{5-fluoro-7-[(2S)-oxolan-2-yl]-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl}pyridin-2-yl)-2-(4-fluorophenyl)butanamide;

4,4,4-trifluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

(2R)-4,4,4-trifluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

(2S)-4,4,4-trifluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]pyridin-2-yl}butanamide;

4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-4-(2,2,2-trifluoroethoxy)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-4-(2,2,2-trifluoroethoxy)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

(2S)-4,4-difluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-4-(2,2,2-trifluoroethoxy)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

4,4,4-trifluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-4-(2,2,2-trifluoroethoxy)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

(2R)-4,4,4-trifluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-4-(2,2,2-trifluoroethoxy)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

(2S)-4,4,4-trifluoro-2-(4-fluorophenyl)-N-{4-[7-(pyridin-2-yl)-4-(2,2,2-trifluoroethoxy)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}butanamide;

N-{4-[4-(cyclopropylmethoxy)-7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2R)—N-{4-[4-(cyclopropylmethoxy)-7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

(2S)—N-{4-[4-(cyclopropylmethoxy)-7-(pyridin-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]pyridin-2-yl}-4,4-difluoro-2-(4-fluorophenyl)butanamide;

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

6 . A method of preparing a compound of general formula (I) according to claim 1 , said method comprising reacting an intermediate compound of general formula (VII-A):

wherein A, X, Y and Z 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 Ha1 represents F, C 1 or Br, or

c) an anhydride of formula

wherein R 2 and R 3 are as defined for the compound of general formula (I) according to claim 1 ,

to give a compound of general formula (I):

wherein R 2 , R 3 , A, X, Y and Z are as defined for the compound of general formula (I) according to claim 1 .

7 . A method of treating or preventing a hyperproliferative disease and/or a disorder responsive to induction of cell death in a subject, comprising administering a compound of general formula (I) according to claim 1 to the subject.

8 . The method according to claim 7 , wherein the hyperproliferative disease and/or disorder responsive to induction of cell death are a haematological tumour, solid tumour and/or metastases thereof.

9 . The method according to claim 8 , wherein the haematological tumour is a lymphoma and/or metastases thereof.

10 . The method according to claim 9 , wherein the lymphoma is diffuse large B-cell lymphoma and/or metastases thereof.

11 . The method according to claim 8 , wherein the solid tumour is a cervical tumour, a lung tumour, a colon tumour and/or metastases thereof.

12 . The method according to claim 11 , wherein the lung tumour is a lung carcinoma and/or metastases thereof.

13 . The method according to claim 11 , wherein the colon tumour is a colorectal carcinoma and/or metastases thereof.

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

15 . A method of treating haematological tumours, solid tumours and/or metastases thereof in a subject, comprising administering a composition according to claim 14 to the subject.

16 . 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.

17 . An intermediate compound of general formula (IX-Q), (IX-A), (XIV-Q), or (XVII), or a salt thereof:

wherein R 2 , R 3 , A, X, Y and Z are as defined for the compound of general formula (I) according to claim 1 , T represents CF 3 —C(O)—, mesylate, tosylate or Ph-SO 2 —, wherein Ph can be substituted one, two or three times with halogen or a methyl-group or a nitro-group, Q represents a chloro, a bromo or an iodo, and PG represents a protecting group.

18 . A method of preparing a compound of general formula (I) according to claim 1 , said method comprising reacting an intermediate compound of general formula (XIV-Q):

wherein R 2 , R 3 , X, Y and Z are as defined for the compound of general formula (I) according to claim 1 , and Q represents a chloro, a bromo or an iodo,

with a stannane, such as, for example, A-Sn (Bu) 3, a boronic acid A-B (OH) 2 or a boronic acid ester thereof, wherein A is as defined for the compound of general formula (I), in the presence of a palladium catalyst,

to prepare compounds of general formula (I).

19 . A method of preparing a compound of general formula (I) according to claim 1 , said method comprising reacting an intermediate compound of general formula (XVII):

wherein R 2 , R 3 , X, Y and Z are as defined for the compound of general formula (I) according to claim 1 , and T represents CF 3 —C(O)—, mesylate, tosylate or Ph-SO 2 —, wherein Ph can be substituted one, two or three times with halogen, methyl or a nitro, with a suitable bromide A-Br or iodide A-I wherein A is as defined for the compound of general formula (I) in the presence of a palladium catalyst, in a Cacchi reaction, to prepare compounds of general formula (I) or, optionally, to prepare compounds of general formula (I) after removal of the group T.