Piperidylurea compounds and methods of use thereof

A compound having a structure of Formula II:

• or a pharmaceutically acceptable salt thereof, wherein:
• A is phenyl or 5- to 10-membered heteroaryl having 1-4 ring heteroatoms independently selected from N, O, and S;
• X2 is CR7 or N;
• wherein R7, if present, is H, halogen, C1-C3 alkyl, or —NH2;
• X3 is CR8 or N;
• wherein R8, if present, is H, halogen, C1-C3 alkyl, or —NH2;
• X4 is CR9;
• and X5 is CR10;
• wherein R9 and R10 are independently H, halogen, C1-C3 alkyl, or —NH2;
• m is 0, 1, 2, or 3;
• R1 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, phenyl, 4- to 9-membered heterocycloalkyl, 5- to 10-membered heteroaryl, —O—R1a, or -Q-R1b;
• wherein the 4- to 9-membered heterocycloalkyl has 1-2 ring heteroatoms or heteroatom groups independently selected from N, O, S, and S(O)2;
• and the 5- to 10-membered heteroaryl has 1-4 ring heteroatoms independently selected from N, O, and S;
• the phenyl is unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, —CN, C1-C3 alkyl, and C1-C3 haloalkyl;
• and the 5- to 10-membered heteroaryl is unsubstituted or substituted with C1-C6 alkyl;
• Q is C1-C6 alkylene, C1-C6 haloalkylene, or C3-C6 cycloalkylene;
• R1a is C1-C6 alkyl, C3-C6 cycloalkyl, —(C1-C6 alkylene)-(C3-C6 cycloalkyl), —(C1-C6 alkylene)-(4 to 9-membered heterocycloalkyl), or phenyl;
• wherein the 4- to 9-membered heterocycloalkyl has 1-2 ring heteroatoms or heteroatom groups independently selected from N, O, S, and S(O)2;
• and wherein R1a is unsubstituted or substituted with 1-3 halogens;
• and
• R1b is C1-C6 alkoxy, C3-C6 cycloalkyl, or phenyl;
• wherein R1b is unsubstituted or substituted with 1-3 halogens;
• R2 is H or C1-C3 alkyl;
• R3a, R3b, R3c, R3d are each independently H, halogen, or C1-C6 alkyl;
• and R4 is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, —(C1-C4 alkylene)-(C1-C3 alkoxy), or C1-C6 hydroxyalkyl;
• or
• R3c and R4 together form a C1-C2 alkylene group;
• Y is absent or C1-C6 alkylene;
• R5a is C1-C6 alkyl, C3-C8 cycloalkyl, phenyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl;
• wherein the 5- to 10-membered heteroaryl has 1-4 ring heteroatoms independently selected from N, O, and S;
• the 4- to 10-membered heterocycloalkyl has 1-3 ring heteroatoms or ring heteroatom groups independently selected from N, O, S, and S(O)2;
• and R5a is unsubstituted or substituted with 1-4 R5d;
• each R5d when present is independently selected from oxo, halogen, —OH, —NR5bR5c, C1-C6 alkyl, C1-C6 haloalkyl, C1-C3 haloalkoxy, C1-C6 alkoxy, C3-C8 cycloalkyl, C1-C4 hydroxyalkyl, —(C1-C4 alkylene)-(C1-C3 alkoxy), —(C1-C5 alkylene)-(C3-C8 cycloalkyl), —(C1-C6 alkylene)-(4- to 10-membered heterocycloalkyl), —(C1-C4 alkylene)-C(O)N(CH3)2, —S(O)2—(C1-C3 alkyl), —C(O)—(C1-C4 alkyl), —C(O)—(C1-C4 hydroxyalkyl), —C(O)O—(C1-C4 alkyl), —C(O)OH, —C(O)NH2, 4- to 10-membered heterocycloalkyl, and phenyl;
• and each of the 4- to 10-membered heterocycloalkyl independently has 1-3 ring heteroatoms or ring heteroatom groups independently selected from N, O, S, and S(O)2 and is independently unsubstituted or substituted with 1 or 2 substituents independently selected from OH, halo, and C1-C6 alkyl;
• and the C3-C8 cycloalkyl is unsubstituted or substituted with OH;
• or
• two R5d are taken together with the atoms to which they are attached to form phenyl, 5- or 6-membered heteroaryl, or 4- to 6-membered heterocycloalkyl;
• wherein the 5- or 6-membered heteroaryl has 1-2 ring heteroatoms independently selected from N, O, and S;
• the 4- to 6-membered heterocycloalkyl has 1-3 ring heteroatoms or ring heteroatom groups independently selected from N, O, S, and S(O)2;
• and the 4- to 6-membered heterocycloalkyl is unsubstituted or substituted with C1-C6 alkyl;
• and
• R5b and R5c are independently selected from H, C1-C3 alkyl, —C(O)—(C1-C4 alkyl), 4- to 9-membered heterocycloalkyl;
• wherein the 4- to 9-membered heterocycloalkyl has 1-3 ring heteroatoms or ring heteroatom groups independently selected from N, O, S, and S(O)2.