Compounds containing s-n-valeryl-n-{[2'-(1h-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine and (2r,4s)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester moieties and cations

Patent metadata

Field	Value
Publication number	US-2020016109-A1
Application number	US-201916579581-A
Country	US
Kind code	A1
Filing date	Sep 23, 2019
Priority date	Nov 9, 2005
Publication date	Jan 16, 2020
Grant date	—

Abstract

A compound comprising of the angiotensin receptor antagonist (ARB) valsartan, the neutral endopeptidase inhibitor (NEPi) (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methylpentanoic acid ethyl ester and one or more monovalent cations such as Na + useful for the treatment of hypertension and/or heart failure.

First claim

What is claimed is:

1 . An amorphous solid form of a compound comprising anionic (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine, anionic (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester, and sodium cations in a 1:1:3 molar ratio.

2 . A pharmaceutical composition comprising the amorphous solid form according to claim 1 and at least one pharmaceutically acceptable excipient.

3 . A process for preparing the amorphous solid form according to claim 1 , the process comprising:
dissolving (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine or a pharmaceutically acceptable salt thereof, and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester or a pharmaceutically acceptable salt thereof, in a first solvent to form a first solution; dissolving a sodium-containing compound in a second solvent to form a second solution; combining the first and second solutions to form a combined solution; and drying the combined solution.

4 . The process according to claim 3 , wherein the first solvent is different from the second solvent.

5 . An amorphous solid form of a compound comprising anionic (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine, anionic (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester, and sodium cations in a 1:1:3 molar ratio, and water.

6 . A pharmaceutical composition comprising the amorphous solid form according to claim 5 and at least one pharmaceutically acceptable excipient.

7 . A process for preparing the amorphous solid form according to claim 5 , the process comprising:
dissolving (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine or a pharmaceutically acceptable salt thereof, and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester or a pharmaceutically acceptable salt thereof, in a first solvent to form a first solution; dissolving a sodium-containing compound in a second solvent to form a second solution; combining the first and second solutions to form a combined solution; and drying the combined solution.

8 . The process according to claim 7 , wherein the first solvent is different from the second solvent.

9 . An amorphous solid form of a compound comprising anionic (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine, anionic (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester, and sodium cations in a 1:1:3 molar ratio, prepared by a process comprising:
dissolving (S)—N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine or a pharmaceutically acceptable salt thereof, and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester, or a pharmaceutically acceptable salt thereof, in a first solvent to form a first solution;
dissolving a sodium-containing compound in a second solvent to form a second solution;
combining the first and second solutions to form a combined solution; and
drying the combined solution.

10 . The amorphous solid form according to claim 9 , wherein the first solvent is different from the second solvent.

11 . A pharmaceutical composition comprising the amorphous solid form according to claim 9 and at least one pharmaceutically acceptable excipient.

12 . An amorphous solid form of trisodium [3-((1S,3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-(S)-3′-methyl-2′-(pentanoyl{2″-(tetrazol-5-ylate)biphenyl-4′-ylmethyl}amino)butyrate] hemipentahydrate.

13 . A pharmaceutical composition comprising the amorphous solid form according to claim 12 and at least one pharmaceutically acceptable excipient.

Assignees

• Novartis Ag

Inventors

• Feng Lili
• Godtfredsen Sven Erik
• Sutton Paul Allen
• Prashad Mahavir
• Girgis Michael J
• Hu Bin
• Liu Yugang
• Blacklock Thomas J
• Karpinski Piotr Henryk

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P5/42

  for decreasing, blocking or antagonising the activity of mineralocorticosteroids · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P9/08

  Vasodilators for multiple indications · CPC title

• A61P43/00

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