N-(hetero)aryl, 2-(hetero)aryl—substituted acetamides for use as Wnt signaling modulators
View Patent ↗The present invention relates to compounds of formulae 1 and 2 and methods for modulating the Wnt signaling pathway using these compounds, wherein A 1 , A 2 , B, Y and Z all represent rings.
1. A compound having Formula (6):
or a physiologically acceptable salt thereof, wherein:
wherein X 1 , X 2 , X 3 and X 4 is selected from N and CR 7 ;
one of X 5 , X 6 , X 7 and X 8 is N and the others are CH;
X 9 is selected from N and CH;
Z is selected from phenyl, pyrazinyl, pyridinyl, pyridazinyl and piperazinyl; wherein each phenyl, pyrazinyl, pyridinyl, pyridazinyl or piperazinyl of Z is optionally substituted with an R 6 group;
R 1 , R 2 and R 3 are hydrogen;
m is 1;
R 4 is selected from hydrogen, halo, difluoromethyl, trifluoromethyl and methyl;
R 6 is selected from hydrogen, halo and —C(O)R 10 ; wherein R 10 is methyl; and
R 7 is selected from hydrogen, halo, cyano, methyl and trifluoromethyl.
2. The compound of claim 1 , wherein said compound is selected from
or a physiologically acceptable salt thereof.
3. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or a physiologically acceptable salt thereof, and a physiologically acceptable carrier.
4. The compound of claim 1 , wherein said compound is 2-(2′,3-dimethyl-2,4′-bipyridin-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide, or a physiologically acceptable salt thereof.
5. The compound of claim 1 , wherein said compound is N-(2,3′-bipyridin-6′-yl)-2-(2′,3-dimethyl-2,4′-bipyridin-5-yl)acetamide, or a physiologically acceptable salt thereof.
6. The compound of claim 1 , wherein said compound is N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(2′-methyl-3-(trifluoromethyl)-2,4′-bipyridin-5-yl)acetamide, or a physiologically acceptable salt thereof.
7. The compound of claim 1 , wherein said compound is N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(2′-fluoro-3-methyl-2,4′-bipyridin-5-yl)acetamide, or a physiologically acceptable salt thereof.
8. The compound of claim 1 , wherein said compound is 2-(2′-fluoro-3-methyl-2,4′-bipyridin-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide; or a physiologically acceptable salt thereof.
9. The compound of claim 2 , wherein said physiologically acceptable salt is a fumaric acid salt of said compound.
10. The compound of claim 4 , wherein said physiologically acceptable salt is a fumaric acid salt of said compound.
11. The compound of claim 5 , wherein said physiologically acceptable salt is a fumaric acid salt of said compound.
12. The compound of claim 8 , wherein said physiologically acceptable salt is a fumaric acid salt of said compound.
13. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 2 or a physiologically acceptable salt thereof, and a physiologically acceptable carrier.
14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 4 or a physiologically acceptable salt thereof, and a physiologically acceptable carrier.
15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 5 or a physiologically acceptable salt thereof, and a physiologically acceptable carrier.
16. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 6 or a physiologically acceptable salt thereof, and a physiologically acceptable carrier.
17. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 7 or a physiologically acceptable salt thereof, and a physiologically acceptable carrier.
18. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 8 or a physiologically acceptable salt thereof, and a physiologically acceptable carrier.