US 6,958,340 B2Granted

Tyrosine kinase inhibitors

AssigneeMerck & Co., Inc.

InventorsMark T. Bilodeau, Peter J. Manley, Adrienne Balitza, George D. Hartman, Leonard Rodman

Life of this patent

Estimating the term…

Abstract

The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.

Claims12

Dependent claims

A compound selected from

4-(2-Phenyl-1H-imidazol-1-yl)-N-pyridin-4-ylpyrimidin-2-amine;
4-(2-Phenyl-1H-imidazol-1-yl)-N-pyrimidin-4-ylpyrimidin-2-amine;
4-(2-Phenyl-1H-imidazol-1-yl)-N-pyrimidin-2-ylpyrimidin-2-amine;
4-(2-Phenyl-1H-imidazol-1-yl)-N-pyrazin-2-ylpyrimidin-2-amine;
4-(2-Phenyl-1H-imidazol-1-yl)-N-(1,3,4-thiadiazol-2-yl)pyrimidin-2-amine;
N-(5-Methyl-1,3,4-thiadiazol-2-yl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-Isoxazol-3-yl-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3-Methylisoxazol-5-yl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(4-Methyl-1,3-thiazol-2-yl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(2-Methylpyridin-4-yl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(2,6-Dimethylpyridin-4-yl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
4-(2-Phenyl-1H-imidazol-1-yl)-N-pyridin-3-ylpyrimidin-2-amine;
N-(1-Oxidopyndin-3-yl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-[3-Methoxy-5-(trifluoromethyl)phenyl]-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
(3-Methyl-5-{[4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-yl]amino}phenyl)methanol;
N-{3-[(4-Acetylpiperazin-1-yl)methyl]-5-methylphenyl}-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3,5-Dimethylphenyl)-4-(2-pyridin-2-yl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3,5-Dimethylphenyl)-4-(2-pyrimidin-5-yl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3,5-Dimethylphenyl)-4-(2-pyridin-3-yl-1H-imidazol-1-yl)pyrimidin-2-amine;
4-(2-Cyclopropyl-1H-imidazol-1-yl)-N-(3,5-dimethylphenyl)pyrimidin-2-amine;
N-(3,5-Dimethylphenyl)-4-(4-methyl-2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
1-{2-[(3,5-Dimethylphenyl)amino]pyrimidin-4-yl}-1H-imidazole-2-carbonitrile;
N-(3,5-Dimethylphenyl)-4-(2-methyl-1H-imidazol-1-yl)pyrimidin-2-amine;
4-(2-Amino-1H-imidazol-1-yl)-N-(3,5-dimethylphenyl)pyrimidin-2-amine;
N-(2-methylphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(2-methoxyphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(2-fluorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3-chlorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3,5-dichlorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3-fluorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3-methoxyphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3-methylphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3,5-dimethoxyphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(4-chlorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(4-fluorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(4-methoxyphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(4-methylphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-[3,5-bis(trifluoromethyl)phenyl]-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-[3-methyl-5-(trifluoromethyl)phenyl]-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3,5-difluorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
4-(2-phenyl-1H-imidazol-1-yl)-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;
N-(3,5-dimethylphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
4-(2-Phenyl-1H-imidazol-1-yl)-N-pyridin-2-ylpyrimidin-2-amine;
N-{3-[(4-acetylpiperazin-1-yl)methyl]phenyl}-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
4-(2-Chloro-1H-imidazol-1-yl)-N-(3,5-dimethylphenyl)pyrimidin-2-amine;
N-(3,5-Dimethylphenyl)-4-[2-(3-fluorophenyl)-1H-imidazol-1-yl]pyrimidin-2-amine;
or a pharmaceutically acceptable salts thereof.

44 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/485,170Filed 26 Jul 2002 · us provisional application
Priority: 1 Aug 2001
Published: US 2004/0220201 A14 Nov 2004
Granted: 25 Oct 2005
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61P 35/00
Antineoplastic agents
C07D 403/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
C07D 403/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group…

Family

Application60/309,400Us provisional application · filed 1 Aug 2001
US 2004/0220201 A1Pre-grant publication · published 4 Nov 2004
US 6,958,340 B2This patent

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

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Abstract

A compound selected from

4-(2-Phenyl-1H-imidazol-1-yl)-N-pyridin-4-ylpyrimidin-2-amine;
4-(2-Phenyl-1H-imidazol-1-yl)-N-pyrimidin-4-ylpyrimidin-2-amine;
4-(2-Phenyl-1H-imidazol-1-yl)-N-pyrimidin-2-ylpyrimidin-2-amine;
4-(2-Phenyl-1H-imidazol-1-yl)-N-pyrazin-2-ylpyrimidin-2-amine;
4-(2-Phenyl-1H-imidazol-1-yl)-N-(1,3,4-thiadiazol-2-yl)pyrimidin-2-amine;
N-(5-Methyl-1,3,4-thiadiazol-2-yl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-Isoxazol-3-yl-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3-Methylisoxazol-5-yl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(4-Methyl-1,3-thiazol-2-yl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(2-Methylpyridin-4-yl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(2,6-Dimethylpyridin-4-yl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
4-(2-Phenyl-1H-imidazol-1-yl)-N-pyridin-3-ylpyrimidin-2-amine;
N-(1-Oxidopyndin-3-yl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-[3-Methoxy-5-(trifluoromethyl)phenyl]-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
(3-Methyl-5-{[4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-yl]amino}phenyl)methanol;
N-{3-[(4-Acetylpiperazin-1-yl)methyl]-5-methylphenyl}-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3,5-Dimethylphenyl)-4-(2-pyridin-2-yl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3,5-Dimethylphenyl)-4-(2-pyrimidin-5-yl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3,5-Dimethylphenyl)-4-(2-pyridin-3-yl-1H-imidazol-1-yl)pyrimidin-2-amine;
4-(2-Cyclopropyl-1H-imidazol-1-yl)-N-(3,5-dimethylphenyl)pyrimidin-2-amine;
N-(3,5-Dimethylphenyl)-4-(4-methyl-2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
1-{2-[(3,5-Dimethylphenyl)amino]pyrimidin-4-yl}-1H-imidazole-2-carbonitrile;
N-(3,5-Dimethylphenyl)-4-(2-methyl-1H-imidazol-1-yl)pyrimidin-2-amine;
4-(2-Amino-1H-imidazol-1-yl)-N-(3,5-dimethylphenyl)pyrimidin-2-amine;
N-(2-methylphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(2-methoxyphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(2-fluorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3-chlorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3,5-dichlorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3-fluorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3-methoxyphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3-methylphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3,5-dimethoxyphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(4-chlorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(4-fluorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(4-methoxyphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(4-methylphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-[3,5-bis(trifluoromethyl)phenyl]-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-[3-methyl-5-(trifluoromethyl)phenyl]-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
N-(3,5-difluorophenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
4-(2-phenyl-1H-imidazol-1-yl)-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;
N-(3,5-dimethylphenyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
4-(2-Phenyl-1H-imidazol-1-yl)-N-pyridin-2-ylpyrimidin-2-amine;
N-{3-[(4-acetylpiperazin-1-yl)methyl]phenyl}-4-(2-phenyl-1H-imidazol-1-yl)pyrimidin-2-amine;
4-(2-Chloro-1H-imidazol-1-yl)-N-(3,5-dimethylphenyl)pyrimidin-2-amine;
N-(3,5-Dimethylphenyl)-4-[2-(3-fluorophenyl)-1H-imidazol-1-yl]pyrimidin-2-amine;
or a pharmaceutically acceptable salts thereof.

44 more elements

Facts

Application

10/485,170Filed 26 Jul 2002 · us provisional application

Priority

1 Aug 2001

Published

US 2004/0220201 A14 Nov 2004

Granted

25 Oct 2005

Term ends

Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61P 35/00
Antineoplastic agents
C07D 403/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
C07D 403/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group…