IP Library Granted Patent US 8,921,555
Granted Patent B2
US 8,921,555 · App. 13/378,237 · Granted Dec 30, 2014

Substituted-1,3,8-triazaspiro[4.5]decane-2,4-diones

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Quick Facts
Patent No.
US 8,921,555
App. No.
13/378,237
Granted
Dec 30, 2014
Kind
B2
Abstract

The present invention relates to substituted 1,3,8-triazaspiro[4.5]decame-2,4-diones useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.

Claims (132)

1. A compound selected from:

3-biphenyl-4-yl-1-(4-hydroxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-1-pyridin-2-yl-1,3,8-triazaspiro[4.5]decane-2,4-dione;

1-(4-hydroxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-3-phenyl-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-1-phenyl-1,3,8-triazaspiro[4.5]decane-2,4-dione;

2-{3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-1-yl}isonicotinic acid;

3-biphenyl-4-yl-1-(6-fluoropyridin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

6-{3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-1-yl}nicotinonitrile;

3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-1-pyridin-4-yl-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-1-(6-hydroxypyridazin-3-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-1-(5-hydroxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-1-(6-methoxypyridin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-1-(6-hydroxypyridin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

methyl 6-{3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-1-yl}pyridine-2-carboxylate;

6-{3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-1-yl}pyridine-2-carboxylic acid;

1-(4-methoxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-3-[4-(1H-tetrazol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

1-(4-hydroxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-3-[4-(1H-tetrazol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

4-{1-(4-hydroxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}benzoic acid;

3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-1-pyridin-3-yl-1,3,8-triazaspiro[4.5]decane-2,4-dione;

tert-butyl (2-{[3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}-1H-imidazol-1-yl)acetate;

tert-butyl (2-{[3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}-1H-imidazol-1-yl)acetate;

(2-{[3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}-1H-imidazol-1-yl)acetic acid;

3-(2-{[3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}-1H-imidazol-1-yl)propanoic acid;

(2-{[3-biphenyl-4-yl-1-(4-hydroxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}-1H-imidazol-1-yl)acetic acid;

3-(2-{[3-biphenyl-4-yl-1-(4-hydroxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}-1H-imidazol-1-yl)propanoic acid;

4-{1-(4-methoxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}benzonitrile;

ethyl 4-{1-(4-methoxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}benzoate;

3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-1-(2-thienyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-8-[(3-bromopyridin-2-yl)methyl]-1-(4-methoxypyrimidin-2-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

1-(4-methoxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-3-phenyl-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-8-[(3-bromopyridin-2-yl)methyl]-1-(4-hydroxypyrimidin-2-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione;

4-[8-[(3-bromopyridin-2-yl)methyl]-1-(4-hydroxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl]-N-phenylbenzamide;

3-biphenyl-4-yl-1-(4-hydroxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

4-[8-[(3-bromopyridin-2-yl)methyl]-1-(4-hydroxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl]-N-cyclopropylbenzamide;

3-biphenyl-4-yl-8-[(3-bromopyridin-2-yl)methyl]-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-8-[(3-bromopyridin-2-yl)methyl]-1-(4-hydroxypyridin-2-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione;

tert-butyl 2-{[3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}nicotinate;

2-{[3-biphenyl-4-yl-1-(4-hydroxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}nicotinic acid;

3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-8-(1H-tetrazol-5-ylmethyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione;

2-{[3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}nicotinonitrile;

3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-8-{[3-(1H-tetrazol-5-yl)pyridin-2-yl]methyl}-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-1-(2-hydroxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-1-(3-hydroxypyridin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

4′-{1-(6-hydroxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylic acid;

3-biphenyl-4-yl-1-(5-hydroxypyrazin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

Butyl 4-{[3-biphenyl-4-yl-1-(4-hydroxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}-1-H-imidazole-5-carboxylate;

Butyl 4-{[3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}-1-H-imidazole-5-carboxylate;

Butyl 4-{[3-biphenyl-4-yl-1-(6-methoxypyrimidin-4-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}-1-H-imidazole-5-carboxylate;

3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-8-[(5-methyl-1-H-imidazol-4-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

4-{([3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}-1-H-imidazole-5-carboxylic acid;

4-[(3-biphenyl-4-yl-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl)methyl]-1-H-imidazole-5-carboxylic acid;

4-{[3-biphenyl-4-yl-1-(6-hydroxypyrimidin-4-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}-1-H-imidazole-5-carboxylic acid;

3-biphenyl-4-yl-1-(6-hydroxypyrimidin-4-yl)-8-[(5-methyl-1-H-imidazol-4-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

2-{[3-biphenyl-4-yl-1-(6-hydroxypyrimidin-4-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]methyl}nicotinic acid;

3-biphenyl-4-yl-1-(4,6-dihydroxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-1-(4-hydroxy-6-methoxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-1-(4,6-dimethoxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-1-(2-hydroxypyridin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

2-{3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-1-yl}pyrimidine-4-carboxylic acid;

6-{3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-1-yl}nicotinic acid;

Methyl 4′-{8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylate;

Methyl 4-[(3-biphenyl-4-yl-2,4-dioxo-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]dec-8-yl)methyl]-1-H-imidazole-5-carboxylate;

4′-{8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylic acid;

4-[(3-biphenyl-4-yl-2,4-dioxo-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]dec-8-yl)methyl]-1-H-imidazole-5-carboxylic acid;

5-(4-{8-[(3-carboxypyridin-2-yl)methyl]-2,4-dioxo-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]dec-3-yl}phenyl)pyridine-2-carboxylic acid;

4′-{8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-3-carboxylic acid;

(4′-{8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-yl)acetic acid;

3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-1-pyrimidin-4-yl-1,3,8-triazaspiro[4.5]decane-2,4-dione;

2-(4-{8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]dec-3-yl}phenyl)cyclopropanecarboxylic acid;

8-[(3-methylpyridin-2-yl)methyl]-1-(6-methoxypyrimidin-4-yl)-3-(4′-propionylbiphenyl-4-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione;

1-(6-hydroxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-3-(4′-propionylbiphenyl-4-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione;

3-biphenyl-4-yl-1-methyl-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

tert-butyl (3-biphenyl-4-yl-2,4-dioxo-1-pyrazin-2-yl-1,3,8-triazaspiro[4.5]dec-8-yl)acetate;

(3-biphenyl-4-yl-2,4-dioxo-1-pyrazin-2-yl-1,3,8-triazaspiro[4.5]dec-8-yl)acetic acid;

(3-biphenyl-4-yl-2,4-dioxo-1-pyrimidin-5-yl-1,3,8-triazaspiro[4.5]dec-8-yl)acetic acid(3-biphenyl-4-yl-2,4-dioxo-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]dec-8-yl)acetic acid;

[3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]acetic acid;

2,2′-(3-biphenyl-4-yl-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-1,8-diyl)diacetic acid;

[3-biphenyl-4-yl-1-(2-ethoxy-2-oxoethyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl]acetic acid;

3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

(3-biphenyl-4-yl-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl)acetic acid;

ethyl 3-biphenyl-4-yl-1-(4-methoxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-6-carboxylate;

ethyl 3-biphenyl-4-yl-1-(4-hydroxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-6-carboxylate;

3-biphenyl-4-yl-1-(4-hydroxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-6-carboxylic acid;

3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-6-carboxylic acid;

Ethyl 3-biphenyl-4-yl-1-(6-hydroxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-6-carboxylate;

3-biphenyl-4-yl-1-(6-hydroxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-6-carboxylic acid;

3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]decane-6-carboxylic acid;

Ethyl 3-biphenyl-4-yl-1-(6-methoxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-6-carboxylate;

Ethyl 3-biphenyl-4-yl-1-(6-hydroxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-6-carboxylate;

3-biphenyl-4-yl-1-(6-hydroxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-6-carboxylic acid;

3-biphenyl-4-yl-1-(6-hydroxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-6-carboxylic acid;

ethyl [({3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-6-yl}carbonyl)amino]acetate;

tert-butyl [({3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-6-yl}carbonyl)amino]acetate;

[({3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-6-yl}carbonyl)amino]acetic acid;

2-[({3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-1-yl}carbonyl)amino]-2-methylpropanoic acid;

(2R)-2-[({3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-1-yl}carbonyl)amino]propanoic acid;

(2S)-2-[({3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-1-yl}carbonyl)amino]propanoic acid;

N-({3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-1-yl}carbonyl)-L-serine;

4-{3-biphenyl-4-yl-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-1-yl}-4-oxobutanoic acid;

4′-{1-(6-methoxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylic acid;

4′-{1-(6-methoxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}-2-methybiphenyl-4-carboxylic acid;

4′-{1-(6-methoxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}-3-methylbiphenyl-4-carboxylic acid;

2-fluoro-4′-{1-(6-methoxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylic acid;

2-methyl-4′-{8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-pyrazin-2-yl-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylic acid;

2-methyl-4′-{1-(6-methylpyrazin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylic acid;

4′-{1-(6-methylpyrazin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylic acid;

2-methyl-4′-[8-[(3-methylpyridin-2-yl)methyl]-1-(6-methylpyrimidin-4-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl]biphenyl-4-carboxylic acid;

4′-[8-[(3-methylpyridin-2-yl)methyl]-1-(6-methylpyrimidin-4-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl]biphenyl-4-carboxylic acid;

2-methyl-4′-{8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-[6-(trifluoromethyl)pyrimidin-4-yl]-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylic acid;

1-(6-methoxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-3-[4′-(1H-pyrazol-5-yl) biphenyl-4-yl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

1-(6-hydroxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-3-[4′-(1H-pyrazol-5-yl) biphenyl-4-yl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

1-(6-methoxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-3-[4′-(5-oxopyrazolidin-3-yl)biphenyl-4-yl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

1-(6-hydroxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-3-[4′-(1 morpholin-4-yl) biphenyl-4-yl]-1,3,8-triazaspiro[4.5]decane-2,4-dione;

4-(6-{3-(4-bromophenyl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-1-yl}pyrimidin-4-yl)benzoic acid;

4′-{8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-pyrimidin-4-yl-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylic acid;

methyl 2-methyl-4′-{8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-pyrimidin-4-yl-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylate;

2-methyl-4′-{8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-pyrimidin-4-yl-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylic acid;

2-methyl-4′-[8-[(3-methylpyridin-2-yl)methyl]-1-(2-methylpyrimidin-4-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl]biphenyl-4-carboxylic acid;

2-methyl-4′-{8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-pyridazin-3-yl-1,3,8-triazaspiro[4.5]dec-3-yl}biphenyl-4-carboxylic acid;

4-(5-{1-(6-methoxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}-pyridin-2-yl)benzoic acid;

4-(5-{1-(4-methoxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}-pyridin-2-yl)benzoic acid;

4-(5-{8-[(4-methoxypyridin-2-yl)methyl]-1-(6-methoxypyrimidin-4-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}-pyridin-2-yl)benzoic acid;

4-(5-{8-[(4-hydroxypyridin-2-yl)methyl]-1-(6-methoxypyrimidin-4-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}-pyridin-2-yl)benzoic acid;

4-(5-{1-(6-methoxypyrimidin-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}-pyridin-2-yl)-3-methylbenzoic acid;

4-(5-{1-(4-methoxypyrimidin-2-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}-pyridin-2-yl)-3-methylbenzoic acid;

3-methyl-4-(5-{8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-(2,2,2-trifluoroethyl)-1,3,8-triazaspiro[4.5]dec-3-yl}-pyridin-2-yl)benzoic acid;

3-fluoro-4-(5-{1-(6-methoxypyrimidine-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl}pyridin-2-yl)-3-benzoic acid;

or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of the stereoisomer thereof.

2. A pharmaceutical composition comprising a compound of claim 1 and pharmaceutically acceptable carrier.

3. A method of enhancing endogenous production of erythropoietin in a mammal which comprises administering to the mammal an amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, that is effective for enhancing endogenous production of erythropoietin.

4. A method for the prevention or treatment of anemia in a mammal which comprises administering to the mammal an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignments (2)
MERGER Recorded Aug 8, 2022
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 061102/0145 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 27, 2014
From: PIERCE, JOAN M.; HALE, JEFFREY J.; MIAO, SHOUWU; VACHAL, PETR
To: MERCK SHARP & DOHME CORP.
Reel/Frame 032541/0464 →