Pyrazolyl-substituted heteroaryls and their use as medicaments

Patent metadata

Field	Value
Publication number	US-9845314-B2
Application number	US-201615255283-A
Country	US
Kind code	B2
Filing date	Sep 2, 2016
Priority date	Sep 11, 2015
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

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 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 (F), —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.

2. The compound of formula 1 or of formula 1′ of claim 1 , wherein
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 methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, —C 1-6 -fluoroalkyl, cyclopropyl, cyclobutyl, cyclopentyl, —C 1-2 -alkylene-C 3-6 -cyclopropyl, —C 1-2 -alkylene-C 3-6 -cyclobutyl, —C 1-2 -alkylene-C 3-6 -cyclopentyl, a five- or six-membered monocyclic heterocycle with 1 oxygen-atom, a 9- to 10-membered bicyclic heterocycle with 1 or 2 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 F, Cl, Br, methyl, ethyl, —CN
wherein R 2 is selected from the group consisting of methyl, ethyl, isopropyl, —CF 3 , F, Br, Cl,
and the pharmaceutically acceptable salts of the aforementioned compounds.

3. The compound of formula 1 or of formula 1′ of claim 1 , wherein
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 methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, —(CH 2 ) 2 —CF 3 , —CH 2 —CH 2 F, cyclopropyl, cyclobutyl, cyclopentyl, -methylene-C 3-6 -cyclopropyl, tetrahydrofuranyl, tetrahydropyranyl, hexahydrofuropyranyl,
wherein R 3 is optionally substituted by one, two, three or four substituents each independently from each other selected from the group consisting of F, Cl, Br, methyl, ethyl, —CN
wherein R 2 is selected from the group consisting of methyl and F,
and the pharmaceutically acceptable salts of the aforementioned compounds.

4. The compound of formula 1 or of formula 1′ of claim 1 , wherein R 2 is methyl,
and the pharmaceutically acceptable salts of the aforementioned compounds.

5. The compound of formula 1 or of formula 1′ of claim 1 , wherein R 2 is F,
and the pharmaceutically acceptable salts of the aforementioned compounds.

6. The compound of formula 1 or of formula 1′ of claim 1 , wherein R 3 is a substituent in meta-position of the pyrazolyl-ring of formula 1,
and the pharmaceutically acceptable salts of the aforementioned compounds.

7. The compound of formula 1 or of formula 1′ of claim 1 , wherein R 3 is a substituent in ortho-position of the pyrazolyl-ring of formula 1,
and the pharmaceutically acceptable salts of the aforementioned compounds.

8. The compound of formula 1 or of formula 1′ of claim 1 , wherein R 3 is substituted by one, two, three or four substituents each independently from each other selected from the group consisting of F, methyl and —CN,
and the pharmaceutically acceptable salts of the aforementioned compounds.

9. The compound of formula 1 or of formula 1′ of claim 1 ,
wherein A is either N or CH,
wherein Y is —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 methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, —(CH 2 ) 2 —CF 3 , —CH 2 —CH 2 F,
wherein R 3 is optionally substituted by one, two, three or four substituents each independently from each other selected from the group consisting of F, methyl and —CN
and the pharmaceutically acceptable salts of the aforementioned compounds.

10. The compound of formula 1 or of formula 1′ of claim 1 , which is selected from the group consisting of

and the pharmaceutically acceptable salts of the aforementioned compounds.

11. The compound of formula 1 or of formula 1′ of claim 1 ,
wherein A is either N or CH,
wherein Y is either —O— or CH 2 ,
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 isopropyl, isobutyl and t-butyl,
wherein R 3 is not further substituted,
and the pharmaceutically acceptable salts of the aforementioned compounds.

12. The compound of formula 1 or of formula 1′ of claim 11 , which is selected from the group consisting of

and the pharmaceutically acceptable salts of the aforementioned compounds.

13. The compound of formula 1 or of formula 1′ of claim 12 , which is

and the pharmaceutically acceptable salts of the aforementioned compound.

14. The compound of formula 1 or of formula 1′ of claim 12 , which is

and the pharmaceutically acceptable salts of the aforementioned compound.

15. The compound of formula 1 or of formula 1′ of claim 12 , which is

and the pharmaceutically acceptable salts of the aforementioned compound.

16. The compound of formula 1 or of formula 1′ of claim 12 , which is

and the pharmaceutically acceptable salts of the aforementioned compound.

17. The compound of formula 1 or of formula 1′ of claim 12 , which is

and the pharmaceutically acceptable salts of the aforementioned compound.

18. The compound of formula 1 or of formula 1′ of claim 12 , which is

and the pharmaceutically acceptable salts of the aforementioned compound.

19. The compound of formula 1 or of formula 1′ of claim 12 , which is

and the pharmaceutically acceptable salts of the aforementioned compound.

Assignees

• Boehringer Ingelheim Int
• Boehrnger Ingelheim Int Gmbh

Inventors

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

Classifications

• A61P37/08

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

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P7/06

  Antianaemics · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · 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