US 8,008,503 B2Granted

Methyl-benzimidazole derivatives

AssigneeHoffmann-La Roche Inc.

InventorsGregory Martin Benson, Konrad Bleicher, Uwe Grether, Rainer E Martin, Jean-Marc Plancher, Hans Richter, Sven Taylor, Minmin Yang

Life of this patent

Estimating the term…

Abstract

The invention is concerned with novel substituted benzimidazole derivatives of formula (I) wherein R1 to R10 are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds can be used as medicaments.

Claims20

Dependent claims

A compound selected from the group consisting of:

2,N-Dicyclohexyl-2-[5,6-difluoro-2-(hydroxy-pyridin-2-yl-methyl)-benzoimidazol-1-yl]-acetamide,
2,N-Dicyclohexyl-2-[5,6-difluoro-2-(hydroxy-pyridin-3-yl-methyl)-benzoimidazol-1-yl]-acetamide,
2,N-Dicyclohexyl-2-[5,6-difluoro-2-(1-hydroxy-1-pyridin-2-yl-ethyl)-benzoimidazol-1-yl]-acetamide,
2-[2-(Benzo[1,3]dioxol-5-yl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-2,N -dicyclohexyl-acetamide,
(−)-2-[2-(Benzo[1,3]dioxol-5-yl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-2,N -dicyclohexyl-acetamide,
(+)-2-[2-(Benzo[1,3]dioxol-5-yl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-2,N -dicyclohexyl-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide,
2-Benzo[1,3]dioxol-5-yl-N-cyclohexyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl) -benzoimidazol-1-yl]-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-(3-Chloro-phenyl)-N-cyclohexyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl) -benzoimidazol-1-yl]-acetamide,
N-Cyclohexyl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide,
2-Benzo[1,3]dioxol-5-yl-N-cyclohexyl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro -benzoimidazol-1-yl]-acetamide,
N-Cyclohexyl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-(3-Chloro-phenyl)-N-cyclohexyl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro -benzoimidazol-1-yl]-acetamide,
N-Cyclopentyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide,
2-Benzo[1,3]dioxol-5-yl-N-cyclopentyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl) -benzoimidazol-1-yl]-acetamide,
N-Cyclopentyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-(3-Chloro-phenyl)-N-cyclopentyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl) -benzoimidazol-1-yl]-acetamide,
2-[2-(Cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N-cyclopentyl-2-(4-methoxy-phenyl)-acetamide,
2-Benzo[1,3]dioxol-5-yl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N-cyclopentyl-acetamide,
2-[2-(Cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N-cyclopentyl-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-(3-Chloro-phenyl)-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N-cyclopentyl-acetamide,
2-[6-Chloro-5-fluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-N-cyclohexyl-2-(4-methoxy-phenyl)-acetamide,
2-(6-Chloro-benzo[1,3]dioxol-5-yl)-2-[6-chloro-5-fluoro-2-(methoxy-phenyl-methyl) -benzoimidazol-1-yl]-N-cyclohexyl-acetamide,
2-[6-Chloro-5-fluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-N-cyclohexyl-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-[6-Chloro-5-fluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(3-chloro-phenyl) -N-cyclohexyl-acetamide,
2-[6-Chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro-benzoimidazol-1-yl]-N -cyclohexyl-2-(4-methoxy-phenyl)-acetamide,
2-Benzo[1,3]dioxol-5-yl-2-[6-chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro -benzoimidazol-1-yl]-N-cyclohexyl-acetamide,
2-(6-Chloro-benzo[1,3]dioxol-5-yl)-2-[6-chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro-benzoimidazol-1-yl]-N-cyclohexyl-acetamide,
2-[6-Chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro-benzoimidazol-1-yl]-2-(3-chloro-phenyl) -N-cyclohexyl-acetamide,
2-[6-Chloro-5-fluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-N-cyclopentyl-2-(4-methoxy-phenyl)-acetamide,
2-(6-Chloro-benzo[1,3]dioxol-5-yl)-2-[6-chloro-5-fluoro-2-(methoxy-phenyl-methyl) -benzoimidazol-1-yl]-N-cyclopentyl-acetamide,
2-[6-Chloro-5-fluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-N-cyclopentyl-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-[6-Chloro-5-fluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(3-chloro -phenyl)-N-cyclopentyl-acetamide,
2-[6-Chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro-benzoimidazol-1-yl]-N -cyclopentyl-2-(4-methoxy-phenyl)-acetamide,
2-Benzo[1,3]dioxol-5-yl-2-[6-chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro -benzoimidazol-1-yl]-N-cyclopentyl-acetamide,
2-[6-Chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro-benzoimidazol-1-yl]-N -cyclopentyl-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-[6-Chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro-benzoimidazol-1-yl]-2-(3-chloro -phenyl)-N-cyclopentyl-acetamide,
2,N-Dicyclohexyl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((R)-2,2,2-trifluoro-1-methoxy-1-phenyl-ethyl) -benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((S)-2,2,2-trifluoro-1-methoxy-1-phenyl-ethyl) -benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide,
2-[2-(Benzo[1,3]dioxol-5-yl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N -cyclohexyl-2-(4-methoxy-phenyl)-acetamide,
2-Cyclohexyl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N -cyclopentyl-acetamide,
N-Cyclopentyl-2-[5,6-difluoro-2-((S)-2,2,2-trifluoro-1-methoxy-1-phenyl-ethyl) -benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide,
2-[2-(Benzo[1,3]dioxol-5-yl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N -cyclopentyl-2-(4-methoxy-phenyl)-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(tetrahydro-thiopyran-4-yl)-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-3-(tetrahydro-thiopyran-4-yl)-propionamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(tetrahydro-thiopyran-4-yl)-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-3-(tetrahydro-thiopyran-4-yl)-propionamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(1,1-dioxo-hexahydro-1-thiopyran-4-yl)-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(1,1-dioxo-hexahydro-1-thiopyran-4-yl)-acetamide, and
N-Cyclohexyl-2-[5,6-difluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-3-(1,1-dioxo-hexahydro-1-thiopyran-4-yl)-propionamide,
or a pharmaceutically acceptable salt or ester thereof.

50 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/862,823Filed 25 Aug 2010 · division
Priority: EP 0712073715 Nov 2007
Published: US 2010/0331371 A130 Dec 2010
Granted: 30 Aug 2011
Term ends: Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07D 235/06
Benzimidazoles; Hydrogenated benzimidazoles: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 3/00
Drugs for disorders of the metabolism
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents

Family

Application12/265,049Parent of this division · filed 5 Nov 2008
US 2010/0331371 A1Pre-grant publication · published 30 Dec 2010
US 7,825,258 B2Parent of this division
US 2009/0131482 A1Published application
US 8,008,503 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:

2,N-Dicyclohexyl-2-[5,6-difluoro-2-(hydroxy-pyridin-2-yl-methyl)-benzoimidazol-1-yl]-acetamide,
2,N-Dicyclohexyl-2-[5,6-difluoro-2-(hydroxy-pyridin-3-yl-methyl)-benzoimidazol-1-yl]-acetamide,
2,N-Dicyclohexyl-2-[5,6-difluoro-2-(1-hydroxy-1-pyridin-2-yl-ethyl)-benzoimidazol-1-yl]-acetamide,
2-[2-(Benzo[1,3]dioxol-5-yl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-2,N -dicyclohexyl-acetamide,
(−)-2-[2-(Benzo[1,3]dioxol-5-yl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-2,N -dicyclohexyl-acetamide,
(+)-2-[2-(Benzo[1,3]dioxol-5-yl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-2,N -dicyclohexyl-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide,
2-Benzo[1,3]dioxol-5-yl-N-cyclohexyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl) -benzoimidazol-1-yl]-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-(3-Chloro-phenyl)-N-cyclohexyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl) -benzoimidazol-1-yl]-acetamide,
N-Cyclohexyl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide,
2-Benzo[1,3]dioxol-5-yl-N-cyclohexyl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro -benzoimidazol-1-yl]-acetamide,
N-Cyclohexyl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-(3-Chloro-phenyl)-N-cyclohexyl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro -benzoimidazol-1-yl]-acetamide,
N-Cyclopentyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide,
2-Benzo[1,3]dioxol-5-yl-N-cyclopentyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl) -benzoimidazol-1-yl]-acetamide,
N-Cyclopentyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-(3-Chloro-phenyl)-N-cyclopentyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl) -benzoimidazol-1-yl]-acetamide,
2-[2-(Cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N-cyclopentyl-2-(4-methoxy-phenyl)-acetamide,
2-Benzo[1,3]dioxol-5-yl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N-cyclopentyl-acetamide,
2-[2-(Cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N-cyclopentyl-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-(3-Chloro-phenyl)-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N-cyclopentyl-acetamide,
2-[6-Chloro-5-fluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-N-cyclohexyl-2-(4-methoxy-phenyl)-acetamide,
2-(6-Chloro-benzo[1,3]dioxol-5-yl)-2-[6-chloro-5-fluoro-2-(methoxy-phenyl-methyl) -benzoimidazol-1-yl]-N-cyclohexyl-acetamide,
2-[6-Chloro-5-fluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-N-cyclohexyl-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-[6-Chloro-5-fluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(3-chloro-phenyl) -N-cyclohexyl-acetamide,
2-[6-Chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro-benzoimidazol-1-yl]-N -cyclohexyl-2-(4-methoxy-phenyl)-acetamide,
2-Benzo[1,3]dioxol-5-yl-2-[6-chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro -benzoimidazol-1-yl]-N-cyclohexyl-acetamide,
2-(6-Chloro-benzo[1,3]dioxol-5-yl)-2-[6-chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro-benzoimidazol-1-yl]-N-cyclohexyl-acetamide,
2-[6-Chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro-benzoimidazol-1-yl]-2-(3-chloro-phenyl) -N-cyclohexyl-acetamide,
2-[6-Chloro-5-fluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-N-cyclopentyl-2-(4-methoxy-phenyl)-acetamide,
2-(6-Chloro-benzo[1,3]dioxol-5-yl)-2-[6-chloro-5-fluoro-2-(methoxy-phenyl-methyl) -benzoimidazol-1-yl]-N-cyclopentyl-acetamide,
2-[6-Chloro-5-fluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-N-cyclopentyl-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-[6-Chloro-5-fluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(3-chloro -phenyl)-N-cyclopentyl-acetamide,
2-[6-Chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro-benzoimidazol-1-yl]-N -cyclopentyl-2-(4-methoxy-phenyl)-acetamide,
2-Benzo[1,3]dioxol-5-yl-2-[6-chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro -benzoimidazol-1-yl]-N-cyclopentyl-acetamide,
2-[6-Chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro-benzoimidazol-1-yl]-N -cyclopentyl-3-(tetrahydro-thiopyran-4-yl)-propionamide,
2-[6-Chloro-2-(cyclohexyl-methoxy-methyl)-5-fluoro-benzoimidazol-1-yl]-2-(3-chloro -phenyl)-N-cyclopentyl-acetamide,
2,N-Dicyclohexyl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((R)-2,2,2-trifluoro-1-methoxy-1-phenyl-ethyl) -benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((S)-2,2,2-trifluoro-1-methoxy-1-phenyl-ethyl) -benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide,
2-[2-(Benzo[1,3]dioxol-5-yl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N -cyclohexyl-2-(4-methoxy-phenyl)-acetamide,
2-Cyclohexyl-2-[2-(cyclohexyl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N -cyclopentyl-acetamide,
N-Cyclopentyl-2-[5,6-difluoro-2-((S)-2,2,2-trifluoro-1-methoxy-1-phenyl-ethyl) -benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide,
2-[2-(Benzo[1,3]dioxol-5-yl-methoxy-methyl)-5,6-difluoro-benzoimidazol-1-yl]-N -cyclopentyl-2-(4-methoxy-phenyl)-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(tetrahydro-thiopyran-4-yl)-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-3-(tetrahydro-thiopyran-4-yl)-propionamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(tetrahydro-thiopyran-4-yl)-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-3-(tetrahydro-thiopyran-4-yl)-propionamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(1,1-dioxo-hexahydro-1-thiopyran-4-yl)-acetamide,
N-Cyclohexyl-2-[5,6-difluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(1,1-dioxo-hexahydro-1-thiopyran-4-yl)-acetamide, and
N-Cyclohexyl-2-[5,6-difluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-3-(1,1-dioxo-hexahydro-1-thiopyran-4-yl)-propionamide,
or a pharmaceutically acceptable salt or ester thereof.

50 more elements

Facts

Application

12/862,823Filed 25 Aug 2010 · division

Priority

EP 0712073715 Nov 2007

Published

US 2010/0331371 A130 Dec 2010

Granted

30 Aug 2011

Term ends

Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07D 235/06
Benzimidazoles; Hydrogenated benzimidazoles: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 3/00
Drugs for disorders of the metabolism
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents