Imidazopyridazine compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-11840546-B2
Application number	US-202117344255-A
Country	US
Kind code	B2
Filing date	Jun 10, 2021
Priority date	Jun 12, 2020
Publication date	Dec 12, 2023
Grant date	Dec 12, 2023

Abstract

Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting ALK2 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with ALK2 activity such as cancer.

First claim

What is claimed is:

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from 1-ethyl-1H-imidazol-4-yl and 4-methyl-2H-1,2,3-triazol-2-yl; and
R 2 is selected from (1R,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl and (2-azabicyclo[2.2.2]octan-2-yl)methyl.

2. The compound of claim 1 , wherein the compound of Formula I is selected from:
2-(1-ethyl-1H-imidazol-4-yl)-5-(6-methyl-7-(4-((1R,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)imidazo[1,2-b]pyridazin-3-yl)-1,8-naphthyridine;
2-(4-(3-(7-(1-ethyl-1H-imidazol-4-yl)-1,8-naphthyridin-4-yl)-6-methylimidazo[1,2-b]pyridazin-7-yl)benzyl)-2-azabicyclo[2.2.2]octane; and
2-(4-(6-methyl-3-(7-(4-methyl-2H-1,2,3-triazol-2-yl)-1,8-naphthyridin-4-yl)imidazo[1,2-b]pyridazin-7-yl)benzyl)-2-azabicyclo[2.2.2]octane;
or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein the compound is 2-(1-ethyl-1H-imidazol-4-yl)-5-(6-methyl-7-(4-((1R,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)imidazo[1,2-b]pyridazin-3-yl)-1,8-naphthyridine, or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein the compound is 2-(4-(3-(7-(1-ethyl-1H-imidazol-4-yl)-1,8-naphthyridin-4-yl)-6-methylimidazo[1,2-b]pyridazin-7-yl)benzyl)-2-azabicyclo[2.2.2]octane, or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 , wherein the compound is 2-(4-(6-ethyl-3-(7-(4-methyl-2H-1,2,3-triazol-2-yl)-1,8-naphthyridin-4-yl)imidazo[1,2-b]pyridazin-7-yl)benzyl)-2-azabicyclo[2.2.2]octane, or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.

7. A compound which is 2-(4-Methyl-2H-1,2,3-triazol-2-yl)-5-(6-methyl-7-(4-((1S,5R)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)imidazo[1,2-b]pyridazin-3-yl)-1,8-naphthyridine, or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising a compound of claim 7 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.

Assignees

• Incyte Corp

Inventors

• Pan Jun
• Bai Yu
• Wu Liangxing
• Yao Wenqing

Classifications

• C07D519/00 Primary

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title