Aminopyridine derivatives and their use as selective ALK-2 inhibitors

Patent metadata

Field	Value
Publication number	US-12466808-B2
Application number	US-202117170690-A
Country	US
Kind code	B2
Filing date	Feb 8, 2021
Priority date	Jul 20, 2016
Publication date	Nov 11, 2025
Grant date	Nov 11, 2025

Abstract

The invention relates to a compound of formula (1) in free form or in pharmaceutically acceptable salt form

to pharmaceutical compositions comprising said compound and to the use of said compound in the treatment of heterotopic ossification and fibrodysplasia ossificans progressiva.

First claim

The invention claimed is:

1 . A compound which is 2-amino-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)-5-(4-((1R,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinamide fumarate or a hydrate thereof; wherein the compound is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees-2-theta at angles (±0.2 degrees) of 14.2, 15.6, and 18.0.

2 . A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 1 and one or more pharmaceutically acceptable carriers.

3 . A method of inhibiting ALK-2 receptor activity in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of the compound according to claim 1 .

4 . A method of treating a disorder or disease selected from heterotopic ossification or fibrodysplasia ossificans progressiva, comprising administering to the subject a therapeutically effective amount of the compound according to claim 1 .

5 . The compound according to claim 1 , wherein the compound is 2-amino-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)-5-(4-((1R,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinamide fumarate dihydrate.

6 . The compound of claim 5 , which is crystalline.

7 . The compound of claim 5 having a DSC thermogram which is characterized by an endothermic peak at about 130° C.

8 . The compound of claim 5 characterized by an X-ray powder diffraction pattern having peaks expressed in degrees-2-theta at angles (±0.2 degrees) of 7.0, 14.2, 15.6, 16.2, 18.0, 19.2, and 25.1.

9 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 5 and one or more pharmaceutically acceptable carriers.

10 . A method of inhibiting ALK-2 receptor activity in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of the compound according to claim 5 .

11 . A method of treating heterotopic ossification or fibrodysplasia ossificans progressiva in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound according to claim 5 .

12 . The method of claim 11 , wherein the method comprises treating heterotopic ossification.

13 . The method of claim 11 , wherein the method comprises treating fibrodysplasia ossificans progressiva.

Assignees

• Novartis Ag

Inventors

• Arista Luca
• Babu Sreehari
• Bian Jianwei
• Cui Kai
• Dillon Michael Patrick
• Lattmann Rene
• Li Jialiang
• Liao Lv
• Lizos Dimitrios
• Ramos Rita
• Stiefl Nikolaus Johannes
• Ullrich Thomas
• Usselmann Peggy
• Wang Xiaoyang
• Waykole Liladhar Murlidhar
• Weiler Sven
• Zhang Yubo
• Zhou Yizong
• Zhu Tingying

Classifications

• C07D491/20

  Spiro-condensed systems · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D413/10

  linked by a carbon chain containing aromatic rings · CPC title

• A61P19/08 Primary

  for bone diseases, e.g. rachitism, Paget's disease · CPC title