Salts

Patent metadata

Field	Value
Publication number	US-9926305-B2
Application number	US-201415035165-A
Country	US
Kind code	B2
Filing date	Nov 5, 2014
Priority date	Nov 8, 2013
Publication date	Mar 27, 2018
Grant date	Mar 27, 2018

Abstract

Salts of 1-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl) -2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid of the formula (I), in particular amino acid salts such as the lysine salt and alkali metal salts such as the sodium salt and the potassium salt, processes for their preparation, medicaments comprising them and their use for controlling diseases.

First claim

The invention claimed is:

1. A salt of a compound of formula (I), wherein the compound is 1-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

2. The salt of claim 1 , wherein it is an amino acid salt or alkali metal salt.

3. The salt of claim 1 wherein it is a lysine salt.

4. The salt of claim 1 wherein it is the L-lysine salt.

5. The salt of claim 4 , wherein the X-ray diffractogram of the compound has a peak maximum of the 2 theta angle at 16.9.

6. The salt of claim 4 , wherein the X-ray diffractogram of the compound has peak maxima of the 2 theta angle at 16.9, 22.3 and 20.0.

7. The salt of claim 1 , wherein it is a sodium salt.

8. The salt of claim 7 , wherein the X-ray diffractogram of the compound has a peak maximum of the 2 theta angle at 17.6.

9. The salt of claim 7 , wherein the X-ray diffractogram of the compound has peak maxima of the 2 theta angle at 17.6, 17.9 and 19.1.

10. The salt of claim 1 , wherein it is a potassium salt.

11. The salt of claim 10 , wherein the X-ray diffractogram of the compound has a peak maximum of the 2 theta angle at 23.7.

12. The salt of claim 10 , wherein the X-ray diffractogram of the compound has peak maxima of the 2 theta angle at 23.7, 15.3 and 20.5.

13. A pharmaceutical formulation comprising the salt of claim 1 and no greater proportions of any other form of the compound of the formula (I).

14. A pharmaceutical formulation comprising the salt of claim 1 in more than 90 percent by weight based on the total amount of the compound of the formula (I) present.

15. A method of preparing the salt of claim 1 , which comprises dissolving the compound of the formula (I) in the form of the free acid in an inert solvent and stirring or shaking with a solution of the salt-forming base at a temperature of 10° C. to 60° C.

16. A method of treating a disorder in a human, wherein the disorder is responsive to chymase inhibition and wherein the disorder is selected from the group consisting of a cardiovascular disorder, a kidney disorder, an inflammatory disorder, an allergic disorder and a fibrotic disorder, comprising administering to the human an effective amount of the salt of claim 1 .

17. The method of claim 16 , wherein the disorder is a cardiovascular disorder.

18. The method of claim 17 , wherein the cardiovascular disorder is selected from the group consisting of atherosclerosis, peripheral vascular disorder, cardiac vascular disorder, micro- and macrovascular damage, vasculitis, restenosis, and endothelial dysfunction.

19. The method of claim 16 , wherein the disorder is a kidney disorder.

20. The method of claim 19 , wherein the kidney disorder is selected from the group consisting of acute renal insufficiency, chronic renal insufficiency, acute kidney failure, and chronic kidney failure.

21. The method of claim 16 , wherein the disorder is heart failure, pulmonary hypertension, chronic obstructive pulmonary disease, asthma, kidney failure, nephropathy, a fibrotic disorder of internal organs or dermatological fibroses.

Assignees

• Bayer Pharma AG

Inventors

• Olenik Britta
• Keil Birgit
• Hinz Martin-Holger
• Fürstner Chantal
• Jeske Mario
• Ackerstaff Jens

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title