Use of dopamine D

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Quick Facts

Patent No.: US 8,785,447
App. No.: 11/424,739
Granted: Jul 22, 2014
Kind: B2

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Abstract

The invention relates to the use of dopamine D 3 receptor ligands for the production of drugs for treating renal function disorders.

Claims (323)

1. A method for the treatment of a renal function disorder comprising administering an effective amount of dopamine D 3 receptor antagonists to a patient in need thereof, wherein the renal function disorder is selected from the group consisting of

renal function disorders with glomerular hyperfiltration,

renal function disorders caused by diabetes mellitus,

renal function disorders caused by nonrenal hypertension,

renal function disorders caused by glomerulonephritis,

renal function disorders caused by ascending urinary tract infections,

renal function disorders caused by sickle cell anemia,

renal function disorders caused by compensatory hypertrophy after unilateral nephrectomy, and

renal function disorders caused by mesangial dysfunction.

2. The method as claimed in claim 1 , wherein the receptor antagonist is 5-amino-3-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)-piperazin-1-yl)-2-methylbut-2-eny-1-ylmercapto)-4-methyl-1,2,4-(4H)-triazole or

2-(3-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)propylmercaptopyrimidin-4-ol fumarate.

3. The method of claim 1 , wherein the dopamine D 3 receptor antagonist is selected from the group consisting of

4′-acetylbiphenyl-4-carboxylic acid N-(4-(4-(2-methoxyphenyl)piperazin-1-yl)but-1-yl)amide,

thienyl-2-carboxylic acid N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)but-1-yl)amide,

3-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)but-2-ylmercapto)-4-methyl-5-methylamino-1,2,4-(4H)-triazole,

3-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)2-methyleneprop-1-yl-mercapto)-5-methylamino-1,2,4-(4H)-triazole,

5-amino-3-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)homo-piperazin-1-yl)2-methyl-but-2-en-1-ylmercapto)-4-methyl-1,2,4-(4H)-triazole,

3-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)prop-1-ylmercapto)-4-methyl-5-methylamino-1,2,4-(4H)-triazole,

5-amino-3-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)-piperazin-1-yl)2-methyl-but-2-en-1-ylmercapto)-4-methyl-1,2,4-(4H)-triazole,

5-amino-3-(4-(4-(2-t-butyl-6-n-propyl)pyrimidin-4-yl)piperazin-1-yl)2-methyl-prop-1-en-1-ylmercapto)-4-methyl-1,2,4-(4H)-triazole,

5-amino-3-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)-piperazin-1-yl)2-methyl-but-2-ylmercapto)-4-methyl-1,2,4-(4H)-triazole,

2-(3-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)propoxy-pyrimidin-4-ol,

2-(3-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)propylmercaptopyrimidin-4-ol fumarate,

2-naphthoic acid N-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)homopiperazin-1-yl)but-1-ylamide,

5-amino-3-(4-(4-(2-t-butyl-6-n-propyl)pyrimidin-4-yl)piperazin-1-yl)-2-methylen-prop-1-ylmercapto)-4-methyl-1,2,4-(4H)-triazole,

3-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)prop-1-ylmercapto-5-(2,5-dimethylfur-3-yl)4-methyl-1,2,4-(4H)-triazole,

(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl) homopiperazin-1-yl)prop-1-ylmercapto-4-methyl-5-(4-methylpyrazol-5-yl)1,2,4-(4H)-triazole,

4-methyl-5-phenyl-1,2,4-(4H)-triazole-3-carboxylic acid N-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl) homopiperazin-1-yl)-but-1-yl-amide,

5-amino-2-(8-(4-(3-cyanophenyl) piperazin-1-yl) octyl-1-yl-mercapto) 1,3,4-thiadiazole,

2-(3-(5-(3-(trifluoromethylphenyl)-1,5-diazocin-1-yl)-propyl-mercapto)pyrimidin-4-ol,

3-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)but-1-ylpyrimidin-4-ol,

4-methoxybenzoic acid N-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)homopiperazin-1-yl)but-1-ylamide,

1-benzothiophene-2-carboxylic acid N-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl) piperazin-1-yl)but-1-ylamide,

5-methoxybenzofuran-2-carboxylic acid N-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl) homopiperazin-1-yl)but-1-ylamide,

(E)-N-({2-[(7-cyano-3,4-dihydro-2(1H)-isoquinolinyl)methyl]cyclopropyl}methyl)-3-(1H-indol-5-yl)-2-propenamide and

2-(4-{[(E)-3-(1H-indol-5-yl)-2-propenoyl]amino}butyl)-1,2,3,4-tetrahydro-7-isoquinolinyl trifluoromethanesulfonate.

4. The method of claim 1 , wherein the dopamine D 3 receptor antagonist is selected from the group consisting of

3-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)but-2-ylmercapto)-4-methyl-5-methylamino-1,2,4-(4H)-triazole,

3-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)2-methyleneprop-1-yl-mercapto)5-methylamino-1,2,4-(4H)-triazole,

5-amino-3-(4-(4-(2-t-butyl-6-trifluoromethyl)pyrimidin-4-yl)homopiperazin-1-yl)2-methyl-but-2-en-1-ylmercapto)-4-methyl-1,2,4-(4H)-triazole,