Crystalline forms of an alkoxyimidazol-1-ylmethyl biphenyl carboxylic acid

Patent metadata

Field	Value
Publication number	US-9249105-B2
Application number	US-201414317060-A
Country	US
Kind code	B2
Filing date	Jun 27, 2014
Priority date	Nov 10, 2010
Publication date	Feb 2, 2016
Grant date	Feb 2, 2016

Abstract

The invention provides crystalline salt forms of 4′-{2-ethoxy-4-ethyl-5-[((S)-2-mercapto-4-methylpentanoylamino)methyl]-imidazol-1-ylmethyl}-3′-fluorobiphenyl-2-carboxylic acid. This invention also provides pharmaceutical compositions comprising the crystalline compounds, processes and intermediates for preparing the crystalline compounds, and methods of using the crystalline compounds to treat diseases such as hypertension.

First claim

What is claimed is:

1. A solid pharmaceutical composition comprising a blended mixture of a pharmaceutically acceptable carrier and a crystalline heminapadisylate salt of 4′-{2-ethoxy-4-ethyl-5-[((S)-2-mercapto-4-methylpentanoylamino)methyl]imidazol-1-ylmethyl}-3′-fluorobiphenyl-2-carboxylic acid, characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 4.84±0.20, 9.41±0.20, 10.82±0.20, 17.39±0.20, 24.17±0.20, and 24.65±0.20; wherein said composition is shaped or loaded into tablets or capsules.

2. The pharmaceutical composition of claim 1 , wherein the crystalline heminapadisylate salt is further characterized by having one or more additional diffraction peaks at 2θ values selected from 14.05±0.20, 18.65±0.20, 19.55±0.20, 20.21±0.20, 21.44±0.20, 23.48±0.20, 25.69±0.20, 26.65±0.20, 28.79±0.20, 29.63±0.20, and 30.52±0.20.

3. The pharmaceutical composition of claim 1 , wherein the crystalline heminapadisylate salt 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. 11 .

4. The pharmaceutical composition of claim 1 , wherein the crystalline heminapadisylate salt is characterized by a differential scanning calorimetry thermogram which has a melting point of about 181° C.

5. The pharmaceutical composition of claim 1 , wherein the crystalline heminapadisylate salt is characterized by a differential scanning calorimetry thermogram substantially in accordance with that shown in FIG. 12 .

6. The pharmaceutical composition of claim 1 , further comprising a secondary therapeutic agent selected from diuretics, β 1 adrenergic receptor blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, AT 1 receptor antagonists, neprilysin inhibitors, non-steroidal anti-inflammatory agents, prostaglandins, anti-lipid agents, anti-diabetic agents, anti-thrombotic agents, renin inhibitors, endothelin receptor antagonists, endothelin converting enzyme inhibitors, aldosterone antagonists, angiotensin-converting enzyme/neprilysin inhibitors, and combinations thereof.

7. A method for treating hypertension or heart failure, comprising administering the pharmaceutical composition of claim 1 to a patient in need of treatment.

Assignees

• Fatheree Paul R
• Thalladi Venkat R
• Theravance Biopharma R&D Ip Llc

Inventors

• Fatheree Paul R
• Thalladi Venkat R

Classifications

• C07D233/70 Primary

  One oxygen atom · CPC title

• A61P9/04

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

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P43/00

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

• A61K31/4164

  1,3-Diazoles · CPC title