Substituted 1H-pyrrolo[3,2-b]pyridine compounds and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12565496-B2
Application number	US-202118018221-A
Country	US
Kind code	B2
Filing date	Jul 27, 2021
Priority date	Jul 29, 2020
Publication date	Mar 3, 2026
Grant date	Mar 3, 2026

Abstract

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

First claim

The invention claimed is:

1 . A compound of formula (I)

wherein:
A represents a group selected from:

X represents N, C—H, C—F, C 1 -C 1 , 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 represents 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 hydrogen, halogen, methoxy, cyano, C 1 -C 2 -alkyl, or C 1 -C 3 -alkoxy-C 1 -C 3 -alkyl-;
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 represents 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 hydrogen, C 1 -C 2 -alkyl, or C 1 -C 2 -alkoxy-C 1 -C 2 -alkyl-;
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 represents N;
R 1b represents hydrogen or fluoro;
R 1e represents hydrogen;
R 1f represents hydrogen;
R 1g represents hydrogen or fluoro;
R 2 represents hydrogen, methyl, or C 1 -alkoxy-C 1 -C 2 -alkyl-;
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—, 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 selected from:
2-(4-fluorophenyl)-N-{4-[5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}propanamide; (2R)-2-(4-fluorophenyl)-N-{4-[5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}propanamide; (2S)-2-(4-fluorophenyl)-N-{4-[5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}propanamide; 2-(4-fluorophenyl)-N-{4-[5-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide; 2-(4-fluorophenyl)-N-{4-[3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide 2-(4-fluorophenyl)-N-{4-[3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}propanamide; (2R)-2-(4-fluorophenyl)-N-{4-[3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}propanamide; (2S)-2-(4-fluorophenyl)-N-{4-[3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}propanamide; 2-(4-fluorophenyl)-N-{4-[6-fluoro-3-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide; 2-(4-fluorophenyl)-N-[4-(6-flu

Assignees

• Bayer Ag
• Broad Inst Inc
• Dana Farber Cancer Inst Inc

Inventors

• Schulze Volker
• Mengel Anne
• Faria Alvares De Lemos Adelaide Clara
• Christian Sven
• Bömer Ulf
• Hillig Roman
• Lechner Christian
• Mortier Jérémie Xavier
• Kaulfuss Stefan
• Corsello Steven
• Handing Katarzyna
• Madec Amael
• Furst Laura
• Shekhar Mrinal
• Berger Markus
• Rupaimoole Rajesha
• Lienau Philip
• Orsi Douglas
• Mckinney David
• Brzezinka Krzysztof

Classifications

• C07D487/04

  Ortho-condensed systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title