N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as WNT signaling modulators

1. A compound having Formula (5):

an N-oxide derivative, or a physiologically acceptable salt thereof, wherein:

wherein A 1 is piperazinyl substituted with —C(O)CH 3 ,

 or selected from:

ring E is phenyl or one of X 1 , X 2 , X 3 and X 4 is N and the others are CR 7 ;

one of X 5 , X 6 , X 7 and X 8 is N and the others are CR 11 ;

Z is a 6-membered heterocycle or a 6-membered heteroaryl, each containing 1-2 nitrogen heteroatoms and each of which is optionally substituted with 1-2 R 6 groups;

R 1 , R 2 and R 3 are H;

R 4 and R 6 are independently hydrogen, cyano, C 1-6 alkoxy, —S(O) 2 R 10 , —C(O)NR 8 R 9 , -L -C(O)R 10 , -L-C(O)OR 10 , C 1-6 alkyl optionally substituted with halo, C 2-6 alkenyl or C 2-6 alkynyl;

R 5 is H or C 1-6 alkyl;

L is a bond or (CR 2 ) 1-4 wherein R is H or C 1-6 alkyl;

W is C 3-7 cycloalkyl;

R 7 and R 11 are independently H, halo, cyano, C 1-6 alkoxy, —S(O) 2 R 10 , or an optionally halogenated C 1-6 alkyl;

R 8 and R 9 are independently H, -L-W, or C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, each of which may be optionally substituted with halo, amino, hydroxyl, alkoxy or cyano;

R 10 is C 1-6 alkyl or -L-W; and

m, n and p are independently 0-2.

2. The compound of claim 1 , wherein A 1 is piperazinyl substituted with —C(O)CH 3 ,

or selected from:

and m is 0-1.

3. The compound of claim 1 , wherein said compound is selected from:

or a physiologically acceptable salt thereof.

4. A compound selected from: 2-(2-(2′,3-dimethyl-2,4′-bipyridin-5-yl)acetamido)-5-(pyrazin-2-yl)pyridine 1-oxide; and 2′,3-dimethyl-5-(2-oxo-2-(5-(pyrazin-2-yl)pyridin-2-ylamino)ethyl)-2,4′-bipyridine 1′-oxide; or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier.

6. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 3 or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier.

7. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 4 or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier.