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-9388134-B2
Application number	US-201414311788-A
Country	US
Kind code	B2
Filing date	Jun 23, 2014
Priority date	Nov 9, 2005
Publication date	Jul 12, 2016
Grant date	Jul 12, 2016

Abstract

A method for treatment of a cardiovascular or renal condition or disease with a specific combination, linked pro-drug or a compound of an angiotensin receptor antagonist and a NEPi.

First claim

What is claimed is:

1. A method for treatment of a cardiovascular condition or disease, wherein the cardiovascular condition or disease is heart failure or hypertension, in a patient in need thereof comprising administering to the patient a therapeutically effective amount 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.

2. The method according to claim 1 , wherein the heart failure is chronic heart failure.

3. The method according to claim 1 , wherein the condition or disease is hypertension.

4. The method according to claim 1 , wherein the compound 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 is administered in the form of a pharmaceutical composition.

5. The method according to claim 1 , wherein the compound 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 is in the crystalline form.

6. The method according to claim 5 , wherein the compound 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 is characterized by an Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectrum having the following absorption bands expressed in reciprocal wave numbers (cm−1)(±2 cm−1): 1711 (st), 1637 (st), 1597 (st) and 1401 (st).

7. The method according to claim 5 , wherein the compound 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 is characterized by an Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectrum having the following absorption bands expressed in reciprocal wave numbers (cm−1)(±2 cm−1): 2956 (w), 1711 (st), 1637 (st), 1597 (st), 1488 (w), 1459 (m), 1401 (st), 1357 (w), 1295 (m), 1266 (m), 1176 (w), 1085 (m), 1010 (w), 942(w), 907 (w), 862 (w), 763 (st), 742 (m), 698 (m), 533 (st).

8. The method according to claim 5 , wherein the compound 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 is characterized by an X-ray powder diffraction pattern taken with a Scintag XDS2000 powder diffractometer comprising the following interlattice plane intervals:
d in [Å] (±0.1 Å): 21.2(s), 17.0(w), 7.1(s), 5.2(w), 4.7(w), 4.6(w), 4.2(w), 3.5(w), 3.3(w).

9. The method according to claim 5 , wherein the compound 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 is characterized by an X-ray powder diffraction pattern taken with a Scintag XDS2000 powder diffractometer comprising the following interlattice plane intervals, 2θ in [°]) (±0.2°) 4.5, 5.5, 5.6, 9.9, 12.8, 15.7, 17.0, 17.1, 17.2, 18.3, 18.5, 19.8, 21.5, 21.7, 23.2, 23.3, 24.9, 25.3, 27.4, 27.9, 28.0, 30.2.

10. The method according to claim 5 , wherein the compound 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 is in the form of a monoclinic unit cell, wherein its cell content comprises twelve formula units of C48H55N6O8Na3.2.5H2O.

11. The method according to claim 10 , wherein the compound 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 is in the form of a monoclinic unit cell, wherein the cell content of the monoclinic unit cell comprises two asymmetric units on two-fold positions.

12. The method according to claim 10 , wherein the monoclinic unit cell has a P2i space group.

13. The method according to claim 5 , wherein the compound 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 is characterized by
sum formula C48H55N6O8Na3.2.5H2O
molecular mass 957.99
crystal colour colourless
crystal shape tabular: hexagonal
crystal system monoclinic
space group P21
Cell parameters
a=20.344 Å
b=42.018 Å
c=20.374 Å
α=90 0
β=119.29
γ=90 o

volume of unit cell 15190.03 Å3
Z (the number of asymmetric units in the unit cell) 2
calculated density 1.26845 g/cm3.

14. The method according to claim 5 , wherein the compound 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 has the sum formula C48H55N6O8Na3.2.5H2O and is in the form of an asymmetric unit comprising six C48H55N6O8Na3.2.5H2O formula units.

15. The method according to claim 5 , wherein the compound 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 is characterized by an X-ray powder diffraction pattern taken with a Scintag XDS2000 powder diffractometer comprising the following interlattice plane intervals, 2e in [° ]) (±0.2°) 4.5, 5.6, 12.8, 17.0, 17.2, 19.8, 21.5, 27.4.

Assignees

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

• A61P7/12

  Antidiuretics, e.g. drugs for diabetes insipidus (ADH A61P5/10) · CPC title

• A61P9/08

  Vasodilators for multiple indications · CPC title

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P5/42

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

• A61P5/24

  of the sex hormones · CPC title