Urea, amide, and substituted heteroaryl compounds for CBL-B inhibition

A compound of Formula (I)

• or a tautomer of the compound, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein
• R1 and R2 are independently hydrogen, C1-C6 alkyl, halo, or C1-C6 haloalkyl,
• provided that when X is sulfur, R1 and R2 are not both hydrogen, and provided that R1 and R2 are not halo when X is sulfur or a bond;
• or
• R1 and R2 are taken together with the carbon atom to which they are attached to form
• X is CR3R4 or sulfur;
• R3 and R4 are independently hydrogen, C1-C6 alkyl, halo, or C1-C6 haloalkyl;
• or
• R1 and R3 are taken together with the carbon atoms to which they are attached to form
• R5 is C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl;
• Z is CH or nitrogen;
• n is zero or one;
• R6 is hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl;
• R7 is C1-C6 alkyl-OH, —(CR8R9)m-(5- to 10-membered monocyclic or fused bicyclic heteroaryl), —(CR8R9)m-(4- to 10-membered monocyclic or fused bicyclic heterocyclyl), —(CR8R9)m—(C6-C10 aryl), or —(CR8R9)m—(C3-C6 cycloalkyl),
• wherein each heteroaryl, heterocyclyl, aryl, or cycloalkyl group is optionally substituted by one to five R10 groups;
• or
• R6 and R7 are taken together with the nitrogen atom to which they are attached to form a 5- to 10-membered monocyclic or fused bicyclic heteroaryl, or a 4- to 10-membered monocyclic or fused bicyclic heterocyclyl, wherein each heteroaryl or heterocyclyl optionally contains one to two additional heteroatoms selected from the group consisting of nitrogen, sulfur, and oxygen, and wherein each heteroaryl or heterocyclyl is optionally substituted by one to five R10 groups;
• m is zero or one;
• R8 and R9 are independently hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl;
• each R10 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-OH, —CN, C1-C6 alkyl-CN, —O(C1-C6 alkyl), —O(C1-C6 haloalkyl), halo, hydroxy, oxo, —CO2H, —C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl)2, —C(O)NH(C1-C6 haloalkyl), —C(O)O(C1-C6 alkyl), —SO2—(C1-C6 alkyl), —SO2—NH(C1-C6 alkyl), —SO2—N(C1-C6 alkyl)2, —C(O)(C1-C6 alkyl), —(C1-C6 alkylene)-C(O)N(C1-C6 alkyl)2, —(C1-C6 alkylene)-C(O)NH(C1-C6 alkyl), C3-C6 cycloalkyl, 5- to 6-membered heterocyclyl, 5- to 6-membered heteroaryl, —(C1-C6 alkylene)-(5- to 6-membered heterocyclyl), —(C1-C6 alkylene)-(5- to 6-membered heteroaryl), —C(O)-(5- to 6-membered heterocyclyl), —C(O)-(5- to 6-membered heteroaryl), or C6-C10 aryl,
• wherein each cycloalkyl, heterocyclyl, heteroaryl, or aryl group is optionally substituted by one to five R11 groups;
• or
• two R10 groups attached to the same carbon atom are taken together with the carbon atom to which they are attached to form a spiro C3-C6 cycloalkyl or a spiro 4- to 6-membered heterocyclyl, each of which is optionally substituted by one to five R11 groups;
• each R11 is independently C1-C6 alkyl, hydroxy, oxo, or —C(O)(C1-C6 alkyl);
• R12 is hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl;
• or when R6 and R7 are taken together with the nitrogen atom to which they are attached to form a 4- to 10-membered monocyclic or fused bicyclic heterocyclyl optionally containing one to two additional heteroatoms selected from the group consisting of nitrogen, sulfur, and oxygen, R12 is C1-C6 alkylene which connects to the 4- to 10-membered monocyclic or fused bicyclic heterocyclyl to form a 7- to 14-membered fused bicyclic or tricyclic heterocyclyl, wherein each heterocyclyl is optionally substituted by one to five R10 groups;
• and
• each R13 is independently hydrogen, C1-C3 alkyl, C1-C3 alkyl-OH, or C1-C3 haloalkyl.