Tertiary amines for use in the treatment of cardiac disorders

Patent metadata

Field	Value
Publication number	US-9951033-B2
Application number	US-201615380613-A
Country	US
Kind code	B2
Filing date	Dec 15, 2016
Priority date	May 18, 2012
Publication date	Apr 24, 2018
Grant date	Apr 24, 2018

Abstract

The present invention relates to tertiary amines of formula (I) for use in therapy, particularly for use in treating cardiovascular disorders. The compounds have been found to regulate phospholamban phosphorylation by interfering with the A-kinase anchor protein 18delta (AKAP18δ) binding to the PKA substrate phospholamban. The compounds share a tri(alkylaryl/alkylheteroaryl) amine structure.

First claim

The invention claimed is:

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:

wherein
L 1 , L 2 and L 3 independently denote C 1 -C 4 -alkylene optionally substituted with one phenyl;
Ar 1 denotes phenyl substituted with one or more R;
Ar 2 denotes phenyl substituted with one or two R;
Ar 3 denotes phenyl;
R denotes NR 2 R 3 ; and
R 2 and R 3 independently denote H or C 1 -C 4 -alkyl.

2. The compound of claim 1 , wherein L 1 , L 2 and L 3 independently denote C 1 -C 4 -alkylene.

3. The compound of claim 1 , wherein L 1 , L 2 and L 3 denote —CH 2 —.

4. The compound of claim 1 , wherein Ar 1 denotes phenyl substituted with one R.

5. The compound of claim 1 , wherein Ar 2 denotes phenyl substituted with one R.

6. The compound of claim 1 , wherein R 2 and R 3 independently denote C 1 -C 4 -alkyl.

7. The compound of claim 1 , wherein R 2 and R 3 denote methyl.

8. The compound of claim 1 , wherein L 1 , L 2 and L 3 denote —CH 2 —, Ar 1 denotes phenyl substituted with one R, Ar 2 denotes phenyl substituted with one R; and R 2 and R 3 independently denote C 1 -C 4 -alkyl.

9. The compound of claim 1 having the following structure:

10. The compound of claim 1 having the following structure:

11. The compound of claim 1 having the following structure:

Assignees

• Univ Oslo

Inventors

• Tasken Kjetil
• Lygren Birgitte
• Ostensen Ellen
• Klaveness Jo

Classifications

• A61P43/00

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• C07D307/79

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring · CPC title