(2r,4r)-5-(5'-chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-[(5-methyloxazole-2-carbonyl)amino]pentanoic acid

Patent metadata

Field	Value
Publication number	US-2017196841-A1
Application number	US-201615357269-A
Country	US
Kind code	A1
Filing date	Nov 21, 2016
Priority date	Feb 19, 2015
Publication date	Jul 13, 2017
Grant date	—

Abstract

In one aspect, the invention relates to a compound of the structure:

or a pharmaceutically acceptable salt thereof, and a crystalline form of this compound, having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising this compound; methods of using this compound; and processes for preparing this compound.

First claim

1 - 28 . (canceled)

29 . A pharmaceutical composition comprising a compound of the following structure:

or a pharmaceutically acceptable salt thereof, and an AT 1 receptor antagonist or a pharmaceutically acceptable salt thereof;
wherein the AT 1 receptor antagonist is selected from the group consisting of abitesartan, azilsartan, azilsartan medoxomil, benzyllosartan, candesartan, candesartan cilexetil, elisartan, embusartan, enoltasosartan, eprosartan, EXP3174, fonsartan, forasartan, glycyllosartan, irbesartan, isoteoline, losartan, medoxomil, milfasartan, olmesartan, olmesartan medoxomil, opomisartan, pratosartan, ripisartan, saprisartan, saralasin, sarmesin, TAK-591, tasosartan, telmisartan, valsartan, and zolasartan; and
wherein the compound is optionally in a crystalline form.

30 . The pharmaceutical composition of claim 29 , wherein the AT 1 receptor antagonist is selected from the group consisting of azilsartan medoxomil, candesartan cilexetil, eprosartan, irbesartan, losartan, olmesartan medoxomil, saprisartan, tasosartan, telmisartan, and valsartan.

31 . The pharmaceutical composition of claim 29 , wherein the pharmaceutically acceptable salt of the AT 1 receptor antagonist is selected from the group consisting of candesartan cilexetil, eprosartan mesylate, losartan potassium salt, and olmesartan medoxomil.

32 . The pharmaceutical composition of claim 29 , wherein the crystalline form is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 8.48±0.20, 14.19±0.20, 17.03±0.20, 21.15±0.20, and 25.41±0.20.

33 . The pharmaceutical composition of claim 32 , wherein the crystalline form is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 7.51±0.20, 8.48±0.20, 14.19±0.20, 17.03±0.20, 17.62±0.20, 17.87±0.20, 20.59±0.20, 21.15±0.20, 21.88±0.20, 24.45±0.20, 24.78±0.20, 25.41±0.20, 25.67±0.20, 27.67±0.20, and 28.22±0.20.

34 . The pharmaceutical composition of claim 33 , wherein the crystalline form is further characterized by having one or more additional diffraction peaks at 2θ values selected from 16.09±0.20, 18.70±0.20, 19.21±0.20, 19.40±0.20, 21.64±0.20, 22.25±0.20, 26.43±0.20, 28.55±0.20, 30.73±0.20, 31.10±0.20, 32.64±0.20, 33.14±0.20, and 34.46±0.20.

35 . The pharmaceutical composition of claim 29 , wherein the crystalline form is characterized by a powder x-ray diffraction pattern in which the peak positions are substantially in accordance with the peak positions of the pattern shown in FIG. 1 .

36 . The pharmaceutical composition of claim 29 , wherein the crystalline form is characterized by a differential scanning calorimetry trace recorded at a heating rate of 10° C. per minute which shows a maximum in endothermic heat flow at a temperature between about 165° C. and 169° C.

37 . The pharmaceutical composition of claim 29 , wherein the crystalline form is characterized by a differential scanning calorimetry trace substantially in accordance with that shown in FIG. 2 .

Assignees

• Theravance Biopharma R&D Ip Llc

Inventors

• Fleury Melissa
• Hughes Adam D
• Beausoleil Anne-Marie
• Fenster Erik
• Thalladi Venkat R
• Rapta Miroslav

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P43/00

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

• A61P9/12

  Antihypertensives · CPC title

• A61P13/12

  of the kidneys · CPC title