Granted Patent B2

US 12,485,125 · App. 17/461,988 · Granted Dec 2, 2025

Inventors: Antonios Matzouranis (Laval, CA); Denis Garceau (Laval, CA); Roberto Bellini (Laval, CA)

Assignee: GlaxoSmithKline Intellectual Property (No. 3) Limited

A61K31/5377A61K31/437A61K31/4545A61K45/06A61P15/00A61P25/04

Abstract

Claims (29)

1 . A method of treating endometriosis-associated chronic pain in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a P2X3 antagonist, wherein the P2X3 antagonist is a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein Formula (I) is:

R 1 is selected from the group consisting of cyano, halogen, methyl, and ethyl;

R 2 is selected from the group consisting of hydrogen, halogen, methyl, and ethyl;

R 3 is selected from the group consisting of halogen, methyl, and ethyl;

R 4 is selected from the group consisting of hydrogen, halogen, methyl, ethyl, and methoxy; R 5 and R 6 are independently selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, and hydroxy-C 1 -C 6 -alkyl; or

R 5 and R 6 , together with the nitrogen to which they are both attached, form a 5- or 6-member heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, and C 1 -C 4 -alkyl;

R 7 and R 8 are independently selected from the group consisting of hydrogen and C 1 -C 4 -alkyl;

R 9 is selected from the group consisting of C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkyl-C 3 -C 6 -cycloalkyl, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, halo-C 1 -C 6 -alkoxy, and C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl; and

X is selected from the group consisting of a bond, CH 2 , and O.

2 . The method of claim 1 , wherein R 1 is methyl and R 2 is hydrogen.

3 . The method of claim 1 , wherein R 3 and R 4 are fluoro.

4 . The method of claim 1 , wherein X is 0.

5 . The method of claim 1 , wherein the compound corresponds in structure to:

and

R 4 is selected from the group consisting of halogen, methyl, and ethyl.

6 . The method of claim 1 , wherein R 5 is hydrogen and R 6 is C 1 -C 6 -alkyl.

7 . The method of claim 1 , wherein R 6 is methyl.

8 . The method of claim 1 , wherein R 7 and R 8 are hydrogen.

9 . The method of claim 1 , wherein R 9 is C 1 -C 6 -alkoxy.

10 . The method of claim 1 , wherein R 9 is methoxy.

11 . The method of claim 1 , wherein the compound corresponds in structure to:

12 . The method of claim 1 , wherein the compound corresponds in structure to:

13 . The method of claim 2 , wherein the compound corresponds in structure to:

14 . The method of claim 1 , wherein the compound corresponds in structure to:

15 . The method of claim 1 , wherein the compound corresponds in structure to:

16 . The method of claim 1 , wherein the compound corresponds in structure to:

17 . The method of claim 1 wherein the mammal is a human.

18 . The method of claim 1 , further comprising the administration of a second therapeutic agent.

19 . The method of claim 18 , wherein the second therapeutic agent is selected from a hormonal contraceptive, a non-steroidal anti-inflammatory agent (NSAID), a prostaglandin E synthase (PTGES) inhibitor, an interleukin-I receptor-associated kinase 4 (IRAK.4) inhibitor, a prostanoid EP4 receptor antagonist, an aldo-keto reductase 1C3 (AKRIC3) inhibitor, and a prolactin receptor (PRLR) antagonist.

Assignments (6)

Continuity (3)

References Cited (119)