2-(3-ethynylbenzyl)-substituted heterocycle derivatives and related uses

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is —O(C1-C6 alkyl), —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C3-C7 cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein the —O(C1-C6 alkyl), —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C3-C7 cycloalkyl, or 3- to 7-membered heterocycloalkyl is optionally substituted with one or more RX1;
• each RX1 independently is oxo, halogen, —CN, —OH, —O(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;
• Z is —O— or —NRZ—;
• RZ is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 haloalkyl;
• R1 is —OH, —O(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(C1-C6 alkyl), —S(C6-C10 aryl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C6-C10 aryl), —O-(5- to 10-membered heteroaryl), —O—(C3-C10 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), —NH—(C6-C10 aryl), —NH-(5- to 10-membered heteroaryl), —NH—(C3-C10 cycloalkyl), or —NH-(3- to 7-membered heterocycloalkyl), wherein the —O(C1-C6 alkyl), —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(C1-C6 alkyl), —S(C6-C10 aryl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, —O—(C6-C10 aryl), —O-(5- to 10-membered heteroaryl), —O—(C3-C10 cycloalkyl), —O-(3- to 7-membered heterocycloalkyl), —NH—(C6-C10 aryl), —NH-(5- to 10-membered heteroaryl), —NH—(C3-C10 cycloalkyl), or —NH-(3- to 7-membered heterocycloalkyl) is optionally substituted with one or more R1S;
• each R1S independently is oxo, halogen, —CN, —OH, —O(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(C1-C6 alkyl), —SO2(C1-C6 alkyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, or 3- to 7-membered heterocycloalkyl;
• Ar is C6-C10 aryl or 5- to 10-membered heteroaryl, wherein the C6-C10 aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more RA;
• each RA independently is halogen, —CN, —OH, —O(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 haloalkyl;
• R2 is C2-C6 alkynyl optionally substituted with one or more Res;
• each R2S independently is oxo, halogen, —CN, —OH, —O(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(C1-C6 alkyl), —SO2(C1-C6 alkyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein the —O(C1-C6 alkyl), —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(C1-C6 alkyl), —SO2(C1-C6 alkyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, or 3- to 7-membered heterocycloalkyl is optionally substituted with one or more R2SS;
• each R2SS independently is oxo, halogen, —CN, —OH, —NH2, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl, or C1-C6 haloalkyl;
• R4a is H, halogen, —CN, —OH, —O(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 haloalkyl;
• R4b is H, halogen, —CN, —OH, —O(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 haloalkyl;
• R5a and R5b each independently are H, halogen, —CN, —OH, —O(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl, wherein the —O(C1-C6 alkyl), —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more R5S;
• or R5a and R5a, together with the atom they attach to, form C3-C7 cycloalkyl or 3- to 7-membered heterocycloalkyl, wherein the C3-C7 cycloalkyl or 3- to 7-membered heterocycloalkyl is optionally substituted with one or more R5S;
• each R5S independently is halogen, —CN, —OH, —O(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 haloalkyl;
• and
• n is 0, 1, 2, or 3.