Aminopyridine derivatives and their use as selective ALK-2 inhibitors

Patent metadata

Field	Value
Publication number	US-10947218-B2
Application number	US-202016884666-A
Country	US
Kind code	B2
Filing date	May 27, 2020
Priority date	Jul 20, 2016
Publication date	Mar 16, 2021
Grant date	Mar 16, 2021

Abstract

The invention relates to a compound of formula (I) 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 method of inhibiting ALK-2 receptor activity in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of a compound which is 2-amino-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)-5-(4-(3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinamide, or a pharmaceutically acceptable salt thereof.

2. 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 a compound which is 2-amino-N-(4-hydroxybicyclo[2.2.2]octa n-1-yl)-5-(4-(3-(tetrahydro-2H-pyran-4-yl)-3-aza bicyclo[3.1.0]hexan-1-yl)phenyl)nicotinamide, or a pharmaceutically acceptable salt thereof.

3. The method of 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, or a pharmaceutically acceptable salt thereof.

4. The method of claim 1 , wherein the compound is 2-amino-N-(4-hydroxybicyclo-[2.2.2]octan-1-yl)-5-(4-((1S,5R)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl-phenyl)nicotinamide, or a pharmaceutically acceptable salt thereof.

5. The method of claim 2 , wherein the compound is 2-amino-N-(4-hydroxybicyclo-[2.2.2]octan-1-yl)-5-(44(1R,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)-phenyl)nicotinamide, or a pharmaceutically acceptable salt thereof.

6. The method of claim 2 , wherein the compound is 2-amino-N-(4 hydroxybicyclo-[2.2.2]octan-1-yl)-5-(4-((1S,5R)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)-phenyl)nicotinamide, or a pharmaceutically acceptable salt thereof.

7. The method of claim 2 , wherein the disorder or disease is heterotopic ossification.

8. The method of claim 2 , wherein the disorder or disease fibrodysplasia ossificans progressiva.

9. 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 a pharmaceutical composition comprising 2-amino-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)-5-(4-(3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinamide, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

10. The method of claim 9 , wherein the pharmaceutical composition comprises 2-amino-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)-5-(4-((1S,5R)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)-phenyl)nicotinamide, or a pharmaceutically acceptable salt thereof.

11. The method of claim 9 , wherein the pharmaceutical composition comprises 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, or a pharmaceutically acceptable salt thereof.

12. The method of claim 9 , wherein the disorder or disease is heterotopic ossification.

13. The method of claim 9 , wherein the disorder or disease 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

• C07D405/14 Primary

  containing three or more hetero rings · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• C07D401/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D213/82

  in position 3 · CPC title

• A61P19/08 Primary

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