Modulators of beta catenin and uses thereof

A compound having the structural Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is hydrogen, (C1-C4)alkyl, or (C1-C4)alkylene[OP(O)(OH)2];
• R2 is aryl, heteroaryl, heterocyclyl, or cycloalkyl, each of which are optionally substituted with 1 to 3 groups selected from R1A;
• R3 is hydrogen, (C1-C4)alkyl, halo, or (C1-C4)alkylene(C1-C4alkoxy);
• or R2 and R3 are taken together to form C5cycloalkyl substituted with phenyl;
• X is —OR6 or —NR7R8;
• R4 is (C1-C4)alkyl, (C1-C4)alkyl, halo(C1-C4)alkyl, or heterocyclyl when X is —NR7R8, or R4 is hydrogen, (C1-C4)alkyl, halo(C1-C4)alkyl, or heterocyclyl when X is —OR6;
• or R2 and R4 are taken together to form heterocyclyl;
• R6 is cycloalkyl, heterocyclyl, (C1-C4)alkylene(C1-C4alkoxy), (C1-C4)alkylene[aryl], (C1-C4)alkylene[heteroaryl], or (C1-C4)alkylene[cycloalkyl], wherein the aryl is substituted with 1 to 3 groups selected from R2A and the heteroaryl is optionally substituted with 1 to 3 groups selected from R2A;
• R7 is H;
• R8 is cycloalkyl, heterocyclyl, (C1-C4)alkylene(C1-C4alkoxy), (C1-C4)alkylene[aryl], (C1-C4)alkylene[heteroaryl], or (C1-C4)alkylene[cycloalkyl], wherein the cycloalkyl is optionally substituted with 1 to 3 groups selected from R2A;
• or R7 and R8 are taken together to form heterocyclyl or heteroaryl, each of which is optionally substituted with 1 to 3 groups selected from R2A;
• each R1A is independently selected from halo, cyano, (C1-C4)alkyl, hydroxy(C1-C4)alkyl, hydroxy[halo(C1-C4)alkyl], cyano(C1-C4)alkyl, halo(C1-C4)alkyl, (C1-C4)alkoxy, deuterated(C1-C4)alkoxy, (C1-C4)alkoxyO(C1-C4)alkyl, (C1-C4)alkoxyO[deuterated(C1-C4)alkyl], halo(C1-C4)alkoxy, (C1-C4)alkoxyO[halo(C1-C4)alkyl], oxo, hydroxy, —O[hydroxy(C1-C4)alkyl], —O[cycloalkyl], —O[heterocyclyl], —O[aryl], —O[heteroaryl], (C1-C4)alkylene[cycloalkyl], (C1-C4)alkylene[aryl], (C1-C4)alkylene[heterocyclyl], (C1-C4)alkylene[heteroaryl], —O(C1-C4)alkylene[NRaRb], —O(C1-C4)alkylene[NRaC(O)Rb], —O(C1-C4)alkylene[cycloalkyl], —O(C1-C4)alkylene[aryl], —O(C1-C4)alkylene[heterocyclyl], —O(C1-C4)alkylene[heteroaryl], cycloalkyl, heterocyclyl, aryl, heteroaryl, (C1-C4)alkylene(C1-C4)alkoxy, (C1-C4)alkylene[deuterated(C1-C4)alkoxy], (C1-C4)alkylene[halo(C1-C4)alkoxy], (C1-C4)alkoxyO[cycloalkyl], (C1-C4)alkoxyO[heterocyclyl], (C1-C4)alkoxyO[heteroaryl], (C1-C4)alkoxyO[phenyl], —C(O)[heterocyclyl], —SRa, —S(O)Ra, —SO2Ra, —S(O)(NRa)Rb, —NRbSO2Rb, —SO2NRa, —C(O)Ra, —C(O)ORa, —C(O)NRaRb, —NRaC(O)Rb, —NRaC(O)NRb, —NRaRb, —NH(C1-C4)alkylene[heterocyclyl], and (C1-C4)alkyleneNRaRb, where each occurrence of cycloalkyl, heterocyclyl, aryl, and heteroaryl alone, or as part of another group, is optionally substituted with 1 to 3 groups selected from halo, oxo, (C1-C4)alkyl, halo(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy, hydroxy, —NH2, —NH(C1-C4)alkyl, —N((C1-C4)alkyl)2, cycloalkyl, heterocyclyl, aryl, heteroaryl, and CN;
• each R2A is independently selected from halo, (C1-C4)alkyl, halo(C1-C4)alkyl, hydroxy(C1-C4)alkyl, deuterated(C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy, deuterated(C1-C4)alkoxy, (C1-C4)alkylene(C1-C4)alkoxy, (C1-C4)alkylene[deuterated(C1-C4)alkoxy], (C1-C4)alkylene[halo(C1-C4)alkoxy], oxo, —O[cycloalkyl], CN, hydroxy, S(O)(C1-C4)alkyl, —S(O)2(C1-C4)alkyl, hydroxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, (C1-C4)alkylene[cycloalkyl], (C1-C4)alkylene[aryl], (C1-C4)alkylene[heterocyclyl], (C1-C4)alkylene[heteroaryl], —C(O)Ra1, —C(O)ORa1, —C(O)NRa1Rb1, —NRa1C(O)Rb1, —NRa1C(O)NRb1, wherein said heterocyclyl, aryl, heteroaryl, and cycloalkyl are each optionally substituted with 1 to 3 groups selected from halo, (C1-C4)alkyl, halo(C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy, and CN;
• each Ra, Ra1, Rb, and Rb1 is each independently selected from hydrogen, (C1-C4)alkyl, halo(C1-C4)alkyl, (C1-C4)alkylene(C1-C4)alkoxy, (C1-C4)alkyleneNH2, (C1-C4)alkyleneNH((C1-C4alkyl), (C1-C4)alkyleneN((C1-C4alkyl)2, cycloalkyl, and heterocyclyl, wherein the cycloalkyl and heterocyclyl are each optionally substituted with (C1-C4)alkyl, hydroxy, or hydroxy(C1-C4)alkyl.