US 8,835,689 B2Granted

Substituted 4-aminocyclohexane derivatives

AssigneeGrüNenthal GmbH

InventorsBert Nolte, Wolfgang Schröder, Klaus Linz, Werner Englberger, Hans Schick, Heinz Graubaum, Birgit Roloff, Sigrid Ozegowski, József Bálint, Helmut Sonnenschein

Life of this patent

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Abstract

The invention relates to compounds that have an affinity to the μ-opioid receptor and the ORL 1-receptor, methods for their production, medications containing these compounds and the use of these compounds for the treatment of pain and other conditions.

Claims6

Dependent claims

A compound selected from the group consisting of:

N-((-4-(dimethylamino)-1-methyl-4-phenylcyclohexyl)methyl)acetamide;
N-(4-(dimethylamino)-1-(3-methyl-1H-indol-2-yl)-4-phenylcyclohexyl)-N-methyl-cinnamamide;
N-(4-(dimethylamino)-1-(3-methyl-1H-indol-2-yl)-4-phenylcyclohexyl)-N-methylacetamide;
(E)-N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-3-phenyl-acrylamide (non-polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-acetamide (non-polar diastereomer);
(E)-N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-3-phenyl-acrylamide (polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-acetamide (polar diastereomer);
3-benzyl-1-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-1-methyl-urea (non-polar diastereomer);
3-benzyl-1-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-1-methyl-urea (polar diastereomer);
1-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-3-ethyl-1-methyl-urea (non-polar diastereomer);
1-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-3-ethyl-1-methyl-urea (polar diastereomer);
(E)-N-[[4-dimethylamino-4-(3-fluorophenyl)-1-methyl-cyclohexyl]-methyl]-3-phenyl-acrylamide (polar diastereomer);
(E)-N-[[4-dimethylamino-4-(3-fluorophenyl)-1-methyl-cyclohexyl]-methyl]-3-phenyl-acrylamide (non-polar diastereomer);
N-[4-(dimethylamino)-1,4-diphenyl-cyclohexyl]-N-methyl-2,2-diphenyl-acetamide (polar diastereomer);
(E)-N-[4-(cyclopentyl-methyl)-4-dimethylamino-1-phenyl-cyclohexyl]-N-methyl-3-phenyl-acrylamide (non-polar diastereomer);
(E)-N-[4-(cyclopentyl-methyl)-4-dimethylamino-1-phenyl-cyclohexyl]-N-methyl-3-phenyl-acrylamide (polar diastereomer);
(E)-N-[4-dimethylamino-1-(3-methyl-1H-indol-2-yl)-4-phenyl-cyclohexyl]-N-methyl-3-phenyl-acrylamide (polar diastereomer);
N-[4-(dimethylamino)-1,4-diphenyl-cyclohexyl]-N-methyl-pyridin-3-carboxylic acid amide (non-polar diastereomer);
N-[4-(dimethylamino)-1,4-diphenyl-cyclohexyl]-N,1-dimethyl-1H-pyrazol-3-carboxylic acid amide (polar diastereomer);
N-[4-(dimethylamino)-1,4-diphenyl-cyclohexyl]-N,1-dimethyl-1H-pyrazol-3-carboxylic acid amide (non-polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-3-(trifluoromethyl)-benzamide (non-polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-3-(trifluoromethyl)-benzamide (polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-4-methoxy-N-methyl-benzamide (non-polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-4-methoxy-N-methyl-benzamide (polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-3-fluoro-N-methyl-benzamide (non-polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-3-fluoro-N-methyl-benzamide (polar diastereomer);
3-[[4-(dimethylamino)-1,4-diphenyl-cyclohexyl]-methyl-carbamoyl]-propionic acid (polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-cyclohexane carboxylic acid amide (polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-tetrahydro-pyran-4-carboxylic acid amide (polar diastereomer);
and
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N,1-dimethyl-piperidin-4-carboxylic acid amide (polar diastereomer);
and physiologically compatible salts thereof.

29 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/454,256Filed 24 Apr 2012 · continuation
Priority: EP 0800574827 Mar 2008
Published: US 2012/0202810 A19 Aug 2012
Granted: 16 Sep 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification82 codes

C07D 209/20
Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals:…
A61K 31/135
Amines: having aromatic rings , e.g. ketamine, nortriptyline
A61K 31/136
Having aromatic rings , e.g. ketamine, nortriptyline: having the amino group directly attached to the aromatic ring, e.g. benzeneamine
A61K 31/165
Amides, e.g. hydroxamic acids: having aromatic rings, e.g. colchicine, atenolol, progabide

Family

Application12/410,801Parent of this continuation · filed 25 Mar 2009
US 2012/0202810 A1Pre-grant publication · published 9 Aug 2012
US 2009/0247530 A1Published application
US 8,835,689 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound selected from the group consisting of:

N-((-4-(dimethylamino)-1-methyl-4-phenylcyclohexyl)methyl)acetamide;
N-(4-(dimethylamino)-1-(3-methyl-1H-indol-2-yl)-4-phenylcyclohexyl)-N-methyl-cinnamamide;
N-(4-(dimethylamino)-1-(3-methyl-1H-indol-2-yl)-4-phenylcyclohexyl)-N-methylacetamide;
(E)-N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-3-phenyl-acrylamide (non-polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-acetamide (non-polar diastereomer);
(E)-N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-3-phenyl-acrylamide (polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-acetamide (polar diastereomer);
3-benzyl-1-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-1-methyl-urea (non-polar diastereomer);
3-benzyl-1-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-1-methyl-urea (polar diastereomer);
1-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-3-ethyl-1-methyl-urea (non-polar diastereomer);
1-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-3-ethyl-1-methyl-urea (polar diastereomer);
(E)-N-[[4-dimethylamino-4-(3-fluorophenyl)-1-methyl-cyclohexyl]-methyl]-3-phenyl-acrylamide (polar diastereomer);
(E)-N-[[4-dimethylamino-4-(3-fluorophenyl)-1-methyl-cyclohexyl]-methyl]-3-phenyl-acrylamide (non-polar diastereomer);
N-[4-(dimethylamino)-1,4-diphenyl-cyclohexyl]-N-methyl-2,2-diphenyl-acetamide (polar diastereomer);
(E)-N-[4-(cyclopentyl-methyl)-4-dimethylamino-1-phenyl-cyclohexyl]-N-methyl-3-phenyl-acrylamide (non-polar diastereomer);
(E)-N-[4-(cyclopentyl-methyl)-4-dimethylamino-1-phenyl-cyclohexyl]-N-methyl-3-phenyl-acrylamide (polar diastereomer);
(E)-N-[4-dimethylamino-1-(3-methyl-1H-indol-2-yl)-4-phenyl-cyclohexyl]-N-methyl-3-phenyl-acrylamide (polar diastereomer);
N-[4-(dimethylamino)-1,4-diphenyl-cyclohexyl]-N-methyl-pyridin-3-carboxylic acid amide (non-polar diastereomer);
N-[4-(dimethylamino)-1,4-diphenyl-cyclohexyl]-N,1-dimethyl-1H-pyrazol-3-carboxylic acid amide (polar diastereomer);
N-[4-(dimethylamino)-1,4-diphenyl-cyclohexyl]-N,1-dimethyl-1H-pyrazol-3-carboxylic acid amide (non-polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-3-(trifluoromethyl)-benzamide (non-polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-3-(trifluoromethyl)-benzamide (polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-4-methoxy-N-methyl-benzamide (non-polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-4-methoxy-N-methyl-benzamide (polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-3-fluoro-N-methyl-benzamide (non-polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-3-fluoro-N-methyl-benzamide (polar diastereomer);
3-[[4-(dimethylamino)-1,4-diphenyl-cyclohexyl]-methyl-carbamoyl]-propionic acid (polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-cyclohexane carboxylic acid amide (polar diastereomer);
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N-methyl-tetrahydro-pyran-4-carboxylic acid amide (polar diastereomer);
and
N-(4-dimethylamino-1,4-diphenyl-cyclohexyl)-N,1-dimethyl-piperidin-4-carboxylic acid amide (polar diastereomer);
and physiologically compatible salts thereof.

29 more elements

Facts

Application

13/454,256Filed 24 Apr 2012 · continuation

Priority

EP 0800574827 Mar 2008

Published

US 2012/0202810 A19 Aug 2012

Granted

16 Sep 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification82 codes

C07D 209/20
Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals:…
A61K 31/135
Amines: having aromatic rings , e.g. ketamine, nortriptyline
A61K 31/136
Having aromatic rings , e.g. ketamine, nortriptyline: having the amino group directly attached to the aromatic ring, e.g. benzeneamine
A61K 31/165
Amides, e.g. hydroxamic acids: having aromatic rings, e.g. colchicine, atenolol, progabide