NHE3-binding compounds and methods for inhibiting phosphate transport

Patent metadata

Field	Value
Publication number	US-10940146-B2
Application number	US-201916351225-A
Country	US
Kind code	B2
Filing date	Mar 12, 2019
Priority date	Apr 12, 2013
Publication date	Mar 9, 2021
Grant date	Mar 9, 2021

Abstract

Provided are NHE3-binding and/or NHE3-modulating agents having activity as phosphate transport inhibitors, including inhibitors of phosphate transport in the gastrointestinal tract and the kidneys, and methods for their use as therapeutic or prophylactic agent.

First claim

The invention claimed is:

1. A method for inhibiting phosphate uptake in the gastrointestinal tract of a patient in need of phosphate lowering, comprising enterally administering to the patient an effective amount of a compound having the structure of Formula (X):

wherein
NHE is

L is a polyalkylene glycol linker;
n is 2; and
Core is selected from:

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the polyalkylene glycol linker is polyethylene glycol.

3. A method for treating hyperphosphatemia in a subject in need thereof, comprising enterally administering to the patient an effective amount of a compound having the structure of Formula (X):

wherein NHE is

L is a polyalkylene glycol linker;
n is 2; and
Core is selected from:

or a pharmaceutically acceptable salt thereof.

4. The method of claim 3 , wherein the polyalkylene glycol linker is polyethylene glycol.

Assignees

• Ardelyx Inc

Inventors

• Carreras Christopher
• Charmot Dominique
• Jacobs Jeffrey W
• Labonte Eric
• Lewis Jason G

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/4453

  only substituted in position 1, e.g. propipocaine, diperodon · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• A61K31/517

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title