Annelated phenoxyacetamides

Patent metadata

Field	Value
Publication number	US-10221202-B2
Application number	US-201715654301-A
Country	US
Kind code	B2
Filing date	Jul 19, 2017
Priority date	Aug 20, 2015
Publication date	Mar 5, 2019
Grant date	Mar 5, 2019

Abstract

The present invention relates to compounds of formula (I)

wherein R 1 , R 2 , R 3 , and Z − have one of the meanings as indicated in the specification or a pharmaceutically acceptable salt thereof, to the use of compounds of formula (I) as a medicament, to pharmaceutical compositions comprising at least one compound of formula (I), as well as to medicament combinations containing one or more compounds of formula (I).

First claim

The invention claimed is:

1. A compound of formula (I),

wherein
R 1 and R 2 are independently ethyl, 2-hydroxyethyl, 2-tetrahydrofuranylmethyl or 4-tetrahydropyranylmethyl;
R 3 is a moiety NR a R b , wherein R a and R b are independently hydrogen, C 1 -C 4 -alkyl or 1-(2-ethoxyethyl)piperidin-4-yl, wherein C 1 -C 4 -alkyl may carry 1 or 2 substituents selected from the group consisting of: hydroxyl, amino, C 1 -C 4 -alkylamino, di-C 1 -C 4 -alkylamino, (dimethylphosphinoyl)methoxy, 4-(dimethylphosphinoyl)phenyl, 6-methyl-3-hydroxy-pyridin-2-yl and the oxyanion of 6-methyl-3-hydroxy-pyridin-2-yl, provided that at least one of R a and R b is different from hydrogen,
or wherein R a and R b together with the nitrogen they are attached to form a heterocyclic moiety selected from the group consisting of: piperidine and 1-oxothiomorpholinyl, wherein the heterocyclic moiety may carry 1 or 2 NH 2 substituents; and
Z − is selected from the group consisting of: chloride, bromide, iodide, hydroxide, hydrogensulfate, sulfate, nitrate, phosphate, formate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate and p-toluenesulfonate,
or Z − may be absent if R a or R b is C 1 -C 4 -alkyl and carries the oxyanion of 6-methyl-3-hydroxy-pyridin-2-yl;
or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein at least one of R 1 and R 2 is ethyl; or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 2 , wherein both of R 1 and R 2 are ethyl; or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , wherein Z − is chloride, formate, or trifluoroacetate; or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 , wherein R 3 is

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 , selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition comprising at least one compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7 , wherein the composition further comprises as further active substances, one or more compounds selected from the group consisting of: ENaC inhibitors, betamimetics, anticholinergics, corticosteroids, PDE4-inhibitors, LTD4-antagonists, EGFR-inhibitors, dopamine agonists, H1-antihistamines, PAF-antagonists, MAP-kinase inhibitors, MPR4-Inhibitors, iNOS-Inhibitors, SYK-Inhibitors, correctors of the cystic fibrosis transmembrane regulator (CFTR) and CFTR potentiators.

9. The compound according to claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

15. The compound according to claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

17. The compound according to claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

18. The compound according to claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

19. A pharmaceutically acceptable salt of the following parent compound:

20. A pharmaceutically acceptable salt of the following parent compound:

21. A pharmaceutically acceptable salt of the following parent compound:

22. A pharmaceutically acceptable salt of the following parent compound:

23. A pharmaceutically acceptable salt of the following parent compound:

24. A pharmaceutically acceptable salt of the following parent compound:

25. A pharmaceutically acceptable salt of the following parent compound:

26. A pharmaceutically acceptable salt of the following parent compound:

27. A pharmaceutically acceptable salt of the following parent compound:

28. A pharmaceutically acceptable salt of the following parent compound:

Assignees

• Boehringer Ingelheim Int

Inventors

• Heckel Armin
• Hamprecht Dieter
• Kley Joerg
• Wiedenmayer Dieter

Classifications

• A61K31/541

  Non-condensed thiazines containing further heterocyclic rings · CPC title

• C07C53/18

  containing fluorine · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title