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Claims for Patent: 5,238,924

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Claims for Patent: 5,238,924

Title: Treatment of renal diseases with ace inhibitors
Abstract:There is disclosed the use of angiotensin converting enzyme (ACE) inhibitors to alter the progression of renal diseases by affecting intraglomerular hemodynamics and proteinuria; i.e., affecting blood pressure within the functioning, filtering tissue of the kidney and the quantity of albumin in the urine.
Inventor(s): Smith; Ronald D. (Worchester, PA)
Assignee: Merck & Co., Inc. (Rahway, NJ) Brigham & Women's Hospital (Boston, MA)
Application Number:07/721,790
Patent Claims: 1. A method of treating progressive renal failure which is manifested by such deficiences as intraglomerular hypertension, progressive glomerular sclerosis, progressive proteinuria, azotemia, regardless of the etiology of the initial renal insult which method comprises administering to a patient in need of such treatment a renal failure inhibiting amount of an angiotensin converting enzyme inhibitor carboxyalkyl dipeptide compound.

2. The method of claim 1 wherein said angiotensin converting enzyme inhibitor compound is a member selected from the group consisting of carboxyalkyl dipeptide derivatives;

1-(3-mercapto-2-methyl-1-oxopropyl)-L-proline;

2-[N-(S)-1-ethoxy-carbonyl-3-phenylpropyl)-S-alanyl]-cis,endo-2-aza-bicyclo [3,3,0]octane-3(S)-carboxylic acid;

N-((S)-1-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-N-(2-indanyl)-glycine;

1-(N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-cis,syn-octahydro-(H-in dole-2-S)-carboxylic acid;

2-(N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl)-1,2,3,4-tetrahydroiso- isoquinoline-3(S)-carboxylic acid; and,

1-carboxymethyl-3(S)-(1(S)-ethoxycarbonyl-3-phenylpropylamino)-2,3,4,5-tetr ahydro-1H[1]-benzazepine-2-one.

3. The method of claim 2 wherein said carboxyalkyl dipeptide derivatives are selected from the group consisting of:

N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-L-proline;

N-[1(S)-carboxy-3-phenylpropyl]-L-alanyl-L-proline; or,

N-.alpha.-[1(S)-carboxy-3-phenylpropyl]-L-lysyl-L-proline.

4. A method of treating progressive renal failure which is manifested by such deficiencies as intraglomerular hypertension, progressive glomerular sclerosis, progressive proteinuria, azotemia, regardless of the etiology of the initial renal insult which method comprises administering to a person in need of such treatment a renal failure inhibiting amount of an angiotensin converting enzyme inhibitor compound which is a member selected from the group consisting of:

N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-L-proline;

N-[1(S)-carboxy-3-phenylpropyl]-L-alanyl-L-proline; or,

N.alpha.-[1(S)-carboxy-3-phenylpropyl]-L-lysyl-L-proline.

5. A method of treating progressive renal failure that comprises administering to a patient in need of such treatment a renal failure inhibiting amount of an angiotensin converting enzyme inhibitor compound.

6. The method of claim 5 wherein said angiotensin converting enzyme inhibitor compound is a member selected from the group consisting of carboxyalkyl dipeptide derivatives;

1-(3-mercapto-2-methyl-1-oxopropyl)-L-proline;

2-[N-(S)-1-ethoxy-carbonyl-3-phenylpropyl)-S-alanyl]-cis,endo-2-aza-bicyclo [3,3,0]octane-3(S)-carboxylic acid; N-((S)-1-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-N-(2-indanyl)-glycine;

1-(N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-cis,syn-octahydro-(H-in dole-2-S)-carboxylic acid;

2-(N-[(S)-1-ethoxy- carbonyl-3-phenylpropyl]-L-alanyl)1,2,3,4-tetrahydroiso-isoquinoline-3(S)- carboxylic acid; and,

1-carboxymethyl-3(S)- (1(S)-ethoxycarbonyl-3-phenylpropylamino)-2,3,4,5-tetrahydro-1H [1]-benzazepine-2-one.

7. The method of claim 6 wherein said carboxyalkyl dipeptide derivatives are selected from the group consisting of:

N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-L-proline;

N-[1(S)-carboxy-3-phenylpropyl]-L-alanyl-L-proline; or,

N-.alpha.-[1(S)-carboxy-3-phenylpropyl]-L-lysyl-L-proline.

8. A method of treating progressive renal failure that comprises administering to a person in need of such treatment a renal failure inhibiting amount of an angiotensin converting enzyme inhibitor compound which is a member selected from the group consisting of:

N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-L-proline;

N-[1(S)-carboxy-3-phenylpropyl]-L-alanyl-L-proline; or,

N-.alpha.-[1(S)-carboxy-3-phenylpropyl]-L-lysyl-L-proline.

9. The method of claim 1 wherein the progressive renal failure is caused by glomerulonephritis.

10. The method of claim 1 wherein the progressive renal failure is caused by diabetic nephropathy.

11. The method of claim 1 wherein the progressive renal failure is caused by normotensive diabetes.

12. The method of claim 4 wherein the progressive renal failure is caused by glomerulonephritis.

13. The method of claim 4 wherein the progressive renal failure is caused by diabetic nephropathy.

14. The method of claim 4 wherein the progressive renal failure is caused by normotensive diabetes.

15. The method of claim 5 wherein the progressive renal failure is caused by glomerulonephritis.

16. The method of claim 5 wherein the progressive renal failure is caused by diabetic nephropathy.

17. The method of claim 5 wherein the progressive renal failure is caused by normotensive diabetes.

18. The method of claim 8 wherein the progressive renal failure is caused by glomerulonephritis.

19. The method of claim 8 wherein the progressive renal failure is caused by diabetic nephropathy.

20. The method of claim 8 wherein the progressive renal failure is caused by normotensive diabetes.
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