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

A compound having Formula (5):

• or a physiologically acceptable salt thereof, wherein:
• wherein A1 is piperazinyl substituted with —C(O)CH3,
• or selected from:
• ring E is phenyl or one of X1, X2, X3 and X4 is N and the others are CR7;
• one of X5, X6, X7 and X8 is N and the others are CR11;
• 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 R6 groups;
• R1, R2 and R3 are H;
• R4 and R6 are independently hydrogen, cyano, C1-6alkoxy, —S(O)2R10, —C(O)NR8R9, -L-C(O)R10, -L-C(O)OR10, C1-6 alkyl optionally substituted with halo, C2-6 alkenyl or C2-6 alkynyl;
• R5 is H or C1-6 alkyl;
• L is a bond or (CR2)1-4 wherein R is H or C1-6 alkyl;
• W is C3-7cycloalkyl;
• R7 and R11 are independently H, halo, cyano, C1-6alkoxy, —S(O)2R10, or an optionally halogenated C1-6 alkyl;
• R8 and R9 are independently H, -L-W, or C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each of which may be optionally substituted with halo, amino, hydroxyl, alkoxy or cyano;
• or R8 and R9 together with the atoms to which they are attached may form a ring;
• R10 is C1-6 alkyl or -L-W;
• and
• m, n and p are independently 0-2.

A compound having Formula (1) or (2):

• or a physiologically acceptable salt thereof, wherein:
• ring E is an optionally substituted aryl or heteroaryl;
• A1 and A2 are independently a C1-5heterocycle, quinolinyl, or a heteroaryl selected from the group
• wherein any heterocycle of A1 and A2 can be optionally substituted with -LC(O)R10;
• B is benzothiazolyl, quinolinyl or isoquinolinyl, each of which is optionally substituted with 1-3 R6 groups;
• X1, X2, X3 and X4 are independently CR7 or N;
• Y is phenyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazinyl, each of which is optionally substituted with 1-2 R6 groups;
• Z is aryl, C1-5 heterocycle, or a 5-6 membered heteroaryl containing 1-2 heteroatoms selected from N, O and S;
• each Y and Z are optionally substituted with 1-3 R6 groups;
• R1 and R5 are independently H or C1-6 alkyl;
• R2 and R3 are independently H, C1-6 alkyl or halo;
• R4 is halo, cyano, C1-6alkoxy, or a C1-6 alkyl optionally substituted with halo, alkoxy or amino;
• R6 is hydrogen, halo, C1-6alkoxy, —S(O)2R10, —C(O)OR10, —C(O)R10, —C(O)NR8R9, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each of which can be optionally substituted with halo, amino, hydroxyl, alkoxy or cyano;
• halo, CN, -L-W, NR8R9, -L-C(O)R10, -L-C(O)OR10, -L-C(O)NR8R9, OR10;
• -L-S(O)2R10 or -L-S(O)2NR8R9;
• R7 is H, halo, C1-6 alkoxy, -L-S(O)2R10, C1-6 alkyl optionally substituted with halo, amino, hydroxyl, alkoxy or cyano;
• NR8R9, -L-C(O)R10, -L-C(O)NR8R9, OR10;
• -L-S(O)2R10 or -L-S(O)2NR8R9;
• R8 and R9 are independently H, -L-W, or C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each of which may be optionally substituted with halo, amino, hydroxyl, alkoxy or cyano;
• or R8 and R9 together with the atoms to which they are attached may form a ring;
• R10 is H, -L-W, or C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each of which may be optionally substituted with halo, amino, hydroxyl, alkoxy or cyano;
• L is a bond or (CR2)1-4 wherein R is H or C1-6 alkyl;
• W is C3-7cycloalkyl, C1-5heterocycle, aryl or heteroaryl;
• m is 0-4;
• n is 0-3;
• and
• p is 0-2.

A compound selected from:

• N-(6-methoxybenzo[d]thiazol-2-yl)-2-(3-(pyridin-4-yl)phenyl)acetamide;
• N-(6-phenylpyridin-3-yl)-2-(3-(pyridin-4-yl)phenyl)acetamide;
• 2-(3-(2-methylpyridin-4-yl)phenyl)-N-(6-phenylpyridin-3-yl)acetamide;
• N-(6-phenylpyridin-3-yl)-2-(3-(pyridazin-4-yl)phenyl)acetamide;
• 2-(3-(2-methoxypyridin-4-yl)phenyl)-N-(6-phenylpyridin-3-yl)acetamide;
• N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-(2-methylpyridin-4-yl)phenyl)acetamide;
• 2-(3-(2-methylpyridin-4-yl)phenyl)-N-(4-(pyridazin-3-yl)phenyl)acetamide;
• 2-(3-(2-methylpyridin-4-yl)phenyl)-N-(4-(pyrazin-2-yl)phenyl)acetamide;
• 2-(3-(2-methylpyridin-4-yl)phenyl)-N-(6-(pyrazin-2-yl)pyridin-3-yl)acetamide;
• 2-(2′-methyl-2,4′-bipyridin-6-yl)-N-(6-phenylpyridin-3-yl)acetamide;
• 2-(2′-methyl-2,4′-bipyridin-4-yl)-N-(6-phenylpyridin-3-yl)acetamide;
• 2-(4-cyano-3-(2-methylpyridin-4-yl)phenyl)-N-(6-phenylpyridin-3-yl)acetamide;
• N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-cyano-3-(2-methylpyridin-4-yl)phenyl)acetamide;
• 2-(2′-methyl-2,4′-bipyridin-4-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide;
• N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(2′-methyl-2,4′-bipyridin-4-yl)acetamide;
• N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(2-cyano-2′-methyl-3,4′-bipyridin-5-yl)acetamide;
• 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.