Pyrazolyl-substituted heteroaryls and their use as medicaments

Patent metadata

Field	Value
Publication number	US-10155751-B2
Application number	US-201715809163-A
Country	US
Kind code	B2
Filing date	Nov 10, 2017
Priority date	Sep 11, 2015
Publication date	Dec 18, 2018
Grant date	Dec 18, 2018

Abstract

The invention relates to new substituted heteroaryls of formula 1

or of formula 1′

wherein A is either N or CH,

wherein R 2 is selected from the group consisting of —C 1-3 -alkyl, —C 1-3 -haloalkyl, F, Br, Cl,

wherein Y is selected from —O— or —CH 2 —,

and wherein R 3 is defined as in claim 1 , and the pharmaceutically acceptable salts thereof,

and the use of these aforementioned compounds for the treatment of diseases such as asthma, COPD, allergic rhinitis, allergic dermatitis, lupus erythematodes, lupus nephritis and rheumatoid arthritis.

First claim

The invention claimed is:

1. A method for the treatment of a disease which can be treated by inhibition of the SYK enzyme comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula 1 or 1′,

wherein A is either N or CH,
wherein Y is either —O— or CH 2 ,
wherein R 3 is a substituent in ortho- or in meta-position of the pyrazolyl-ring of formula 1 and is selected from the group consisting of linear or branched —C 1-6 -alkyl, —C 1-6 -haloalkyl, —C 3-6 -cycloalkyl, —C 1-4 -alkylene-C 3-6 -cycloalkyl, a five- or six-membered monocyclic heterocycle with 1, 2 or three heteroatoms each independently selected from O, S or N, a nine- to 10-membered bicyclic heterocycle with 1, 2 or 3 heteroatoms each independently selected from O, S or N,
wherein R 3 is optionally substituted by one, two, three or four substituents each independently from each other selected from the group consisting of halogen, —C 1-3 -alkyl, oxo, —CN
wherein R 2 is selected from the group consisting of —C 1-3 -alkyl, —C 1-3 -haloalkyl, F, Br, Cl, and the pharmaceutically acceptable salts of the aforementioned compounds
and wherein the disease is selected from the group consisting of allergic rhinitis, asthma, COPD, B-cell lymphoma, dermatitis, rheumatoid arthritis, ulcerative colitis, lupus erythematodes, lupus nephritis, Crohn's disease, multiple sclerosis, psoriasis, sclerodermy, T-cell lymphoma, systemic sclerosis (SSc), and malaria.

2. The method of claim 1 , wherein R 2 is methyl or a pharmaceutically acceptable salt of one of the aforementioned compounds.

3. The method of claim 1 , wherein R 2 is F or a pharmaceutically acceptable salt of one of the aforementioned compounds.

4. The method of claim 1 , wherein A is N or a pharmaceutically acceptable salt of one of the aforementioned compounds.

5. The method of claim 1 , wherein A is CH or a pharmaceutically acceptable salt of one of the aforementioned compounds.

6. The method of claim 1 , wherein the compound of formula 1 is selected from the group consisting of

and a pharmaceutically acceptable salt of one of the aforementioned compounds.

7. The method of claim 1 , wherein the compound of formula 1 is selected from the group consisting of

and a pharmaceutically acceptable salt of one of the aforementioned compounds.

8. The method of claim 1 , wherein the compound of formula 1 is selected from the group consisting of

and a pharmaceutically acceptable salt of one of the aforementioned compounds.

9. The method of claim 1 , wherein the disease is selected from the group consisting of asthma, COPD, rheumatoid arthritis, systemic sclerosis, ulcerative colitis, Crohn's disease, lupus erythematodes, lupus nephritis, multiple sclerosis and psoriasis.

10. The method of claim 1 , wherein the disease is COPD.

11. The method of claim 1 , wherein the disease is asthma.

Assignees

• Boehringer Ingelheim Int

Inventors

• Hoffmann Matthias
• Dahmann Georg
• Gnamm Christian
• Fandrick Daniel Robert
• Scott John
• Mccarthy Clive

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P7/06

  Antianaemics · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title