IP Library › Granted Patent US 9,006,433

Granted Patent B2

US 9,006,433 · App. 13/635,275 · Granted Apr 14, 2015

Substituted pyrimidines

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Quick Facts

Patent No.: US 9,006,433
App. No.: 13/635,275
Granted: Apr 14, 2015
Kind: B2

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Abstract

The present invention relates to substituted pyrimidines useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.

Claims (132)

1. A compound selected from:

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2,2-diphenylacetamide;

2-chloro-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)benzamide;

3-chloro-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)benzamide;

4-chloro-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)benzamide;

3-(trifluoromethyl)-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)benzamide;

4-(trifluoromethyl)-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)benzamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-(naphthalen-3-yl)acetamide;

2-cyano-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)benzamide;

3-cyano-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)benzamide;

4-cyano-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)benzamide;

2-(trifluoromethyl)-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)benzamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-methoxybenzamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-3-methoxybenzamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-4-methoxybenzamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-(methylsulfonyl)benzamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-3-(methylsulfonyl)benzamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-4-(methylsulfonyl)benzamide;

N-[4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl]biphenyl-2-carboxamide;

N-[4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl]biphenyl-3-carboxamide;

N-[4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl]biphenyl-4-carboxamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-phenoxybenzamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-3-phenoxybenzamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-4-phenoxybenzamide;

2-(2-chlorophenyl)-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)acetamide;

2-(3-chlorophenyl)-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)acetamide;

2-(4-chlorophenyl)-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)acetamide;

2-(3-cyanophenyl)-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)acetamide;

2-(2-(trifluoromethyl)phenyl)-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)acetamide;

2-(3-(trifluoromethyl)phenyl)-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)acetamide;

2-(4-(trifluoromethyl)phenyl)-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)acetamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-(2-methoxyphenyl)acetamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-(3-methoxyphenyl)acetamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-(4-methoxyphenyl)acetamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-phenylpropanamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-phenylbutanamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-3-methyl-2-phenylbutanamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-3-methyl-2-phenylpentanamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-methyl-2-phenylpropanamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-1-phenylcyclopropanecarboxamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-(naphthalen-1-yl)acetamide;

2-(benzo[d][1,3]dioxol-5-yl)-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)acetamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-(pyridin-4-yl)acetamide;

2-(biphenyl-4-yl)-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)acetamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)heptanamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-3-phenylpropanamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-4-phenylbutanamide;

N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)cyclohexanecarboxamide;

tert-butyl4-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-ylcarbamoyl)piperidine-1-carboxylate;

2-cyclohexyl-N-(4-hydroxy-2-(1H-pyrazo101.01-1-yl)pyrimidin-5-yl)acetamide;

tert-butyl 3-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-ylcarbamoyl)piperidine-1-carboxylate;

tert-butyl4-((4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-ylcarbamoyl)methyl)piperidine-1-carboxylate;

tert-butyl 3-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-ylcarbamoyl)pyrrolidine-1-carboxylate;

1,2,3,4-tetrahydro-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)naphthalene-1-carboxamide;

2,3-dihydro-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-1H-indene-1-carboxamide;

1,2,3,4-tetrahydro-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)naphthalene-2-carboxamide;

2,3-dihydro-N-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-1H-indene-2-carboxamide;

4-chloro-N-[4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl]benzenesulfonamide;

1-(4-chlorophenyl)-N-[4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl]methanesulfonamide;

3-chloro-N-[4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl]benzenesulfonamide;

N-[4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl]-1-[4-(trifluoromethyl)phenyl]methanesulfonamide;

1-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-3-phenylurea;

1-benzyl-3-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)urea;

1-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-3-(1-phenylethyl)urea;

1-cyclohexyl-3-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)urea;

1-cyclopentyl-3-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)urea;

tert-butyl-3-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)urea;

3-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-1,1-diphenylurea;

3-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-1-isopropyl-1-phenylurea;

phenyl 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl carbamate;

cyclohexyl 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl carbamate;

cyclopentyl 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl carbamate;

tert-butyl 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl carbamate;

butyl 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl carbamate;

4-methoxyphenyl 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl carbamate;

3,3-dimethylbutyl 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl carbamate;

phenethyl 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl carbamate;

biphenyl-4-yl 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl carbamate;

naphthalen-2-yl 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl carbamate;

1-benzhydryl-3-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)thiourea;

1-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-3-(1-phenylethyl)thiourea;

1-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-3-(2-phenylpropan-2-yl)thiourea;

benzhydryl 4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxylate;

N-(4-hydroxy-2-(pyridin-2-yl)pyrimidin-5-yl)-2,2-diphenylacetamide;

5-(1-phenyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-1-yl)pyrimidin-4-ol;

5-(1-benzyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-1-yl)pyrimidin-4-ol;

5-phenyl-2-(1H-pyrazol-1-yl)pyrimidin-4-ol;

N-(4-chlorophenyl)-2-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)acetamide;

N-cyclohexyl-2-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)acetamide;

2-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)-N-isopropylacetamide;

4-hydroxy-2-(pyridazin-3-yl)-N-tosylpyrimidine-5-carboxamide;

and pharmaceutically acceptable salts and solvates thereof.

2. A compound selected from: