3,5-dichloro,4-(3,4-(cyclo-)alkoxyphenyl)--2-carbonyloxy)ethyl)pyridine derivatives as PDE-4 inhibitors

Patent metadata

Field	Value
Publication number	US-10087176-B2
Application number	US-201415316401-A
Country	US
Kind code	B2
Filing date	Jun 4, 2014
Priority date	Jun 4, 2014
Publication date	Oct 2, 2018
Grant date	Oct 2, 2018

Abstract

The invention relates to novel 3,5-dichloro,4-(3,4-(cyclo-) alkoxyphenyl)-2-carbonyloxy)ethyl)pyridine compounds which are inhibitors of the phosphodiesterase 4 (PDE4) enzyme and muscarinic M3 receptor antagonists, methods of preparing such compounds, compositions containing them and therapeutic use thereof.

First claim

The invention claimed is:

1. A compound, which is selected from the group consisting of:
[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 4-[(3-cyano-5-hydroxy-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;
[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 4-[(3-hydroxy-5-methyl-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;
[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 4-[(2,6-dihydroxy-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;
[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 4-[(2-fluoro-3-hydroxy-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;
[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 4-[3-(N-[(3R)-quinuclidin-3-yl]oxycarbonylanilino)propyl]benzoate;
[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[(2-hydroxy-5-methoxy-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)-methyl]benzoate;
[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[2-(difluoromethyl)-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino]methyl]benzoate;
[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl) ethyl]-4-[[2-(dimethylaminomethyl)-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino]methyl]benzoate; and
[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 4-[3-(2-fluoro-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)propyl]benzoate, or a pharmaceutically acceptable salt of said compound.

2. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt according to claim 1 , either alone or in combination with another active ingredient, in admixture with one or more pharmaceutically acceptable carrier.

3. A method of treating a disease of the respiratory tract characterized by airway obstruction, comprising administering a compound or pharmaceutically acceptable salt according to claim 1 to a subject in need thereof.

4. A method according to claim 3 wherein the disease of the respiratory tract is selected from asthma and COPD.

5. An inhalation device comprising a pharmaceutical composition according to claim 2 .

6. A kit comprising the pharmaceutical composition of claim 2 and a device which may be a single- or multi-dose dry powder inhaler, a metered dose inhaler or a nebulizer.

Assignees

• Chiesi Farm Spa

Inventors

• Amari Gabriele
• Armani Elisabetta
• Riccaboni Mauro
• Rizzi Andrea
• Baker-Glenn Charles
• Blackaby Wesley
• Van De Poel Herve
• Whittaker Ben

Classifications

• A61P11/06

  Antiasthmatics · CPC title

• C07D453/00

  Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids · CPC title

• C07D453/02 Primary

  containing not further condensed quinuclidine ring systems · CPC title