Sodium-hydrogen exchanger 3 inhibitor compounds

Patent metadata

Field	Value
Publication number	US-2022213042-A1
Application number	US-202017611456-A
Country	US
Kind code	A1
Filing date	May 8, 2020
Priority date	May 16, 2019
Publication date	Jul 7, 2022
Grant date	—

Abstract

The present invention relates to sodium-hydrogen exchanger 3 (NHE3) inhibitor compounds of the Formula:

to pharmaceutical compositions comprising the compound and to the use of the compound for the treatment of certain diseases associated with elevated sodium and/or phosphate levels.

First claim

1 . A compound of the formula:

wherein both R are CN or both R are C(O)NH 2 , or a pharmaceutically acceptable salt thereof.

2 . The compound according to claim 1 , wherein both R are C(O)NH 2 , or a pharmaceutically acceptable salt thereof.

3 . The compound according to claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

4 . The compound of claim 1 , wherein the compound is:

5 . The compound of claim 1 , wherein the compound is the dihydrochloride salt of:

6 . A compound which is:

7 . A compound which is the dihydrochloride salt of:

8 . A method of treating a disease selected from the group consisting of chronic kidney disease, hyperphosphatemia, secondary hyperparathyroidism, heart failure, hypertension and cardiovascular disease comprising administering to a mammal in need thereof a therapeutically effective amount of a compound according to claim 7 , or a pharmaceutically acceptable salt thereof.

9 . A method of treating a disease selected from the group consisting of chronic kidney disease, hyperphosphatemia, secondary hyperparathyroidism, heart failure, and cardiovascular disease comprising administering to a mammal in need thereof a therapeutically effective combination of a compound according to claim 7 , or a pharmaceutically acceptable salt thereof, in combination with a compound of the formula:

or a pharmaceutically acceptable salt thereof.

10 . The method of claim 8 wherein the mammal is a human.

11 . The method of claim 8 wherein the mammal is a dog.

12 . The method of claim 8 wherein the mammal is a cat.

13 . A compound according to claim 7 , or a pharmaceutically acceptable salt thereof, for use in therapy.

14 . A compound according to claim 7 , or a pharmaceutically acceptable salt thereof, for use in the treatment of chronic kidney disease, hyperphosphatemia, secondary hyperparathyroidism, heart failure, hypertension or cardiovascular disease.

15 . A compound according to claim 7 , or a pharmaceutically acceptable salt thereof, for use in simultaneous, separate or sequential combination with a compound of the formula:

or a pharmaceutically acceptable salt thereof, in the treatment of chronic kidney disease, hyperphosphatemia, secondary hyperparathyroidism, heart failure or cardiovascular disease.

16 . A compound of the formula:

or a pharmaceutically acceptable salt thereof, for use in simultaneous, separate or sequential combination with the compound according to claim 7 , or a pharmaceutically acceptable salt thereof, in the treatment of chronic kidney disease, hyperphosphatemia, secondary hyperparathyroidism, heart failure or cardiovascular disease.

17 . A pharmaceutical composition comprising a compound according to claim 7 , or a pharmaceutically acceptable salt thereof, with a pharmaceutically acceptable excipient, carrier, or diluent.

18 . The pharmaceutical composition according to claim 17 additionally comprising a compound of the formula:

or a pharmaceutically acceptable salt thereof.

Assignees

• Lilly Co Eli

Inventors

• Gavardinas Kostas
• Jadhav Prabhakar
• Wang Xiaojun
• Wetterau John Rowley

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61K31/472 Primary

  Non-condensed isoquinolines, e.g. papaverine · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61P9/12

  Antihypertensives · CPC title

• C07D217/14 Primary

  other than aralkyl radicals · CPC title