Substituted imidazoles as PLXDC2 ligands

A compound of Formula Y-Z:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• Z is Z1 or Z2;
• Z1 is:
• Z2 is:
• A1 is CR2;
• A2 is CR2;
• A3 is CR2;
• A4 is CR2;
• A5 is CR2;
• A6 is CR2;
• A7 is CR2;
• A8 is CR2;
• A9 is CR2;
• A10 is CR2;
• A11 is —NR2—;
• A12 is N;
• A13 is CR2, —C(R2)2—, N, —NR2—, or —O—;
• A14 is CR2, —C(R2)2—, N, —NR2—, or —O—;
• A15 is CR2, —C(R2)2—, N, —NR2—, or —O—;
• A16 is CR2, —C(R2)2—, N, —NR2—, or —O—;
• A17 is CR2, —C(R2)2—, N, —NR2—, or —O—;
• A18 is CR2, —C(R2)2—, N, —NR2—, or —O—;
• A19 is C, CR2, or N;
• A20 is CR2, —C(R2)2—, N, —NR2—, or —O—;
• A21 is CR2, —C(R2)2—, N, —NR2—, or —O—;
• A22 is CR2, —C(R2)2—, N, —NR2—, or —O—;
• A23 is C, CR2, or N;
• A24 is CR2, —C(R2)2—, N, —NR2—, or —O—;
• A25 is CR2, —C(R2)2—, N, —NR2—, or —O—;
• A26 is C, CR2, or N;
• each is independently a single or double bond;
• L1 is —O—;
• L2 is —NR2—;
• R1 is ═O;
• each R2 is independently H, halogen, CN, NO2, ═O, alkyl, alkenyl, alkynyl, acyl, C(O)OH, C(O)O(alkyl), C(O)O(alkenyl), C(O)O(alkynyl), C(O)O(aryl), NH2, OH, O(alkyl), O(alkenyl), O(alkynyl), OS(O)2alkyl, OS(O)2cycloalkyl, OS(O)2cycloalkenyl, OS(O)2aryl, OS(O)2heteroaryl, O(cycloalkyl), O(cycloalkenyl), O(aryl), O(heteroaryl), SH, S(alkyl), S(alkenyl), S(alkynyl), S(cycloalkyl), S(cycloalkenyl), S(aryl), S(heteroaryl), S(O)alkyl, S(O)cycloalkyl, S(O)cycloalkenyl, S(O)aryl, S(O)heteroaryl, S(O)2alkyl, S(O)2NH2, S(O)2cycloalkyl, S(O)2cycloalkenyl, S(O)2aryl, S(O)2heteroaryl, cycloalkyl, cycloalkenyl, non-aromatic heterocyclyl, aryl, or heteroaryl;
• wherein each alkyl, C(O)O(alkyl), O(alkyl), OS(O)2alkyl, S(alkyl), S(O)alkyl, and S(O)2alkyl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, NO2, alkylene, acyl, C(O)NH2, C(O)OH, C(O)O(alkyl), NH2, OH, O(alkyl), O(aryl), ═O, SH, S(alkyl), S(O)2alkyl, cycloalkyl, non-aromatic heterocyclyl, aryl, and heteroaryl;
• wherein each alkylene substituent optionally and independently contains 1 or 2 heteroatoms;
• wherein each O(alkyl) substituent is optionally and independently substituted with 1, 2, or 3 independently selected Group A substituents;
• wherein each O(aryl) substituent and aryl substituent is optionally and independently substituted with 1, 2, or 3 independently selected Group B substituents;
• and
• wherein each non-aromatic heterocyclyl substituent and heteroaryl substituent is optionally and independently substituted with 1, 2, or 3 independently selected Group C substituents;
• wherein each alkenyl, alkynyl, C(O)O(alkenyl), C(O)O(alkynyl), O(alkenyl), O(alkynyl), OS(O)2cycloalkyl, OS(O)2cycloalkenyl, O(cycloalkyl), O(cycloalkenyl), S(alkenyl), S(alkynyl), S(cycloalkyl), S(cycloalkenyl), S(O)cycloalkyl, S(O)cycloalkenyl, S(O)2cycloalkyl, S(O)2cycloalkenyl, cycloalkyl, and cycloalkenyl is optionally and independently substituted with 1 or more substituents independently selected from the group consisting of halogen, CN, NO2, alkyl, acyl, C(O)NH2, C(O)OH, C(O)O(alkyl), NH2, OH, O(alkyl), O(acyl), O(aryl), ═O, SH, S(alkyl), S(O)2alkyl, cycloalkyl, non-aromatic heterocyclyl, aryl, and heteroaryl;
• wherein each alkyl substituent is optionally and independently substituted with 1, 2, or 3 independently selected Group D substituents;
• wherein each O(alkyl) substituent is optionally and independently substituted with 1, 2, or 3 independently selected Group A substituents;
• wherein each aryl substituent is optionally and independently substituted with 1, 2, or 3 independently selected Group B substituents;
• and
• wherein each O(aryl) substituent, non-aromatic heterocyclyl substituent, and heteroaryl substituent is optionally and independently substituted with 1, 2, or 3 independently selected Group C substituents;
• wherein each C(O)O(aryl), OS(O)2aryl, OS(O)2heteroaryl, O(aryl), O(heteroaryl), S(aryl), S(heteroaryl), S(O)aryl, S(O)heteroaryl, S(O)2aryl, S(O)2heteroaryl, non-aromatic heterocyclyl, aryl, and heteroaryl is optionally and independently substituted with 1 or more substituents independently selected from the group consisting of halogen, CN, NO2, alkyl, alkenyl, alkynyl, acyl, C(O)NH2, C(O)OH, C(O)O(alkyl), NH2, OH, O(alkyl), O(aryl), SH, S(alkyl), S(O)2alkyl, cycloalkyl, non-aromatic heterocyclyl, aryl, and heteroaryl;
• wherein each alkyl substituent is optionally and independently substituted with 1, 2, or 3 independently selected Group D substituents;
• wherein each O(alkyl) substituent is optionally and independently substituted with 1, 2, or 3 independently selected Group A substituents;
• wherein each O(aryl) substituent and aryl substituent is optionally and independently substituted with 1, 2, or 3 independently selected Group B substituents;
• and
• wherein each non-aromatic heterocyclyl substituent and heteroaryl substituent is optionally and independently substituted with 1, 2, or 3 independently selected Group C substituents;
• and
• wherein each C(O)NH2, NH2, and S(O)2NH2 is optionally and independently substituted with 1 or 2 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, acyl, C(O)O(alkyl), C(O)O(alkenyl), C(O)O(alkynyl), S(O)2alkyl, S(O)2alkenyl, S(O)2alkynyl, S(O)2aryl, S(O)2heteroaryl, cycloalkyl, cycloalkenyl, aryl, and heteroaryl;
• each Group A substituent is independently halogen or phenyl, wherein each phenyl is optionally and independently substituted with 1, 2, or 3 independently selected Group B substituents;
• each Group B substituent is independently halogen, CN, NO2, alkyl, or O(alkyl);
• each Group C substituent is independently halogen or alkyl;
• and
• each Group D substituent is independently halogen or O(alkyl).