Bromodomain inhibitors

Patent metadata

Field	Value
Publication number	US-12503446-B2
Application number	US-202017772604-A
Country	US
Kind code	B2
Filing date	Oct 27, 2020
Priority date	Oct 31, 2019
Publication date	Dec 23, 2025
Grant date	Dec 23, 2025

Abstract

The invention relates to compounds according to the general formula (1), and to the use thereof for production of a medicament, especially for treatment of a disorder associated with bromodomains, such as cancer.

First claim

The invention claimed is:

1 . A compound according to formula (1) or a pharmaceutically acceptable salt thereof:

wherein:
X is selected from O or N—R 1 where R 1 is selected from the group consisting of hydrogen, cyano, C 1-6 -alkyl or in each case optionally mono- or poly-C 1-6 -alkyl-substituted C 3-7 -cycloalkyl, aryl, a monocyclic C 5-6 -heteroaryl group comprising a heteroatom selected from N, O or S, or pyrimidyl;
Y is selected from the group consisting of C 1-6 -alkyl, in each case optionally mono- or poly-C 1-6 -alkyl-substituted C 3-7 -cycloalkyl, aryl, a monocyclic C 5-6 -heteroaryl group comprising a heteroatom selected from N, O or S, or pyrimidyl, NH 2 , NHR 2 and/or NR 2 R 3 , where R 2 and R 3 are selected from the group consisting of C 1-6 -alkyl or in each case optionally mono- or poly-C 1-2 -alkyl-substituted C 3-7 -cycloalkyl, aryl, a monocyclic C 5-6 -heteroaryl group comprising a heteroatom selected from N, O or S, or pyrimidyl, or NR 2 R 3 is piperidyl;
Z is selected from cyclohexyl, aryl, a monocyclic C 5-6 -heteroaryl group comprising a heteroatom selected from N, O or S, or pyrimidyl, each unsubstituted or mono- or polysubstituted by C 1-6 -alkyl, C 1-5 -alkoxy or mono- or poly-halogen-substituted C 1-6 -alkyl; and
Me is methyl.

2 . The compound according to claim 1 , wherein:
X is oxygen; Y is selected from the group consisting of C 1-6 -alkyl or in each case optionally mono- or poly-C 1-2 -alkyl-substituted C 3-7 -cycloalkyl, aryl, a monocyclic C 5-6 -heteroaryl group comprising a heteroatom selected from N, O or S, or pyrimidyl; and Z is selected from cyclohexyl, aryl, a monocyclic C 5-6 -heteroaryl group comprising a heteroatom selected from N, O or S, or pyrimidyl, each unsubstituted or mono- or polysubstituted by C 1-6 -alkyl, C 1-5 -alkoxy or mono- or poly-halogen-substituted C 1-6 -alkyl.

3 . The compound according to claim 1 , wherein the compound is selected from the group consisting of the compounds of the following formulae (MF1), (MF2), (MF3) or (MF4):

4 . The compound according to claim 3 , wherein the compound is the(S) enantiomer of the compounds of the formulae (MF1) or (MF2).

5 . The compound according to claim 1 , wherein:
X is N—R 1 where R 1 is selected from the group consisting of hydrogen, cyano, C 1-6 -alkyl and/or in each case optionally mono- or poly-C 1-2 -alkyl-substituted C 3-7 -cycloalkyl, aryl, a monocyclic C 5-6 -heteroaryl group comprising a heteroatom selected from N, O or S, or pyrimidyl; Y is selected from the group consisting of C 1-6 -alkyl and/or in each case optionally mono- or poly-C 1-2 -alkyl-substituted C 3-7 -cycloalkyl, aryl, a monocyclic C 5-6 -heteroaryl group comprising a heteroatom selected from N, O or S, or pyrimidyl; and Z is selected from cyclohexyl, aryl, a monocyclic C 5-6 -heteroaryl group comprising a heteroatom selected from N, O or S, or pyrimidyl, each unsubstituted or mono- or polysubstituted by C 1-6 -alkyl, C 1-5 -alkoxy or mono- or poly-halogen-substituted C 1-6 -alkyl.

6 . The compound according to claim 5 , wherein the compound is selected from the group consisting of the compounds of the following formulae (JHS1), (JHS2) or (JHS3):

7 . The compound according to claim 1 , wherein:
X is oxygen; Y is selected from the group consisting of NH 2 , NHR 2 and NR 2 R 3 , where R 2 and R 3 are selected from the group consisting of C 1-6 -alkyl or in each case optionally mono- or poly-C 1-2 -alkyl-substituted C 3-7 -cycloalkyl, aryl, a monocyclic C 5-6- heteroaryl group comprising a heteroatom selected from N, O or S, or pyrimidyl, or NR 2 R 3 is piperidyl; and Z is selected from cyclohexyl, aryl, a monocyclic C 5-6- heteroaryl group comprising a heteroatom selected from N, O or S, or pyrimidyl, each unsubstituted or mono- or polysubstituted by C 1-6 -alkyl, C 1-5 -alkoxy or mono- or poly-halogen-substituted C 1-6 -alkyl.

8 . The compound according to claim 7 , wherein the compound is selected from the group consisting of the compound of the following formula (JHS4) or one of the enantiomers thereof:

9 . A method of producing a pharmaceutical composition, comprising combining the compound according claim 1 with one or more excipients or vehicles.

10 . A pharmaceutical composition comprising an effective amount of a compound according to claim 1 and one or more pharmaceutically acceptable excipient or vehicle.

11 . A method of treating acute myeloid leukaemia, the method comprising the step of administering to a subject a therapeutically effective amount of a compound according to claim 1 .

12 . A method of treating myeloproliferative neoplasia, the method comprising the step of administering to a subject a therapeutically effective amount of a compound according to claim 1 .

Assignees

• Forschungszentrum Juelich Gmbh

Inventors

• Bolm Carsten
• Frings Marcus
• Schöbel Jan-Hendrik
• Chatain Nicolas
• Altenburg Bianca
• Rossetti Giulia
• Gossen Jonas
• Koschmieder Steffen

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D239/78 Primary

  with hetero atoms directly attached in position 2 · CPC title