A compound of Formula I: or a pharmaceutically acceptable salt or solvate thereof; wherein A is N or C-R 3; R 1 is H, halo, -C 1 -C 6 alkyl, -C 1 -C 6 alkoxy, -C 1 -C 4 haloalkyl, -C 3 -C 6 cycloalkyl, -C 3 -C 6 halocycloalkyl, -C 1 -C 6 alk-O-C 1 -C 6 alkyl, -C 1 -C 6 alk-S -C 1 -C 6 alkyl, - C 1 -C 6 alk-S 2 -C 1 -C 6 alkyl, -CR 6 R 6' CN, -NR 6 R 6', -NHCR 6 R 6' CN, - NHCONR 6 R 6', -NHC OR 7, NHC -C 1 -C 6 alkyl, NHC -C 1 -C 6 haloalkyl, -NH-C 1 -C 6 alk-C -C 1 -C 6 alkyl, -NHC NR 6 R 6', -NH-OR 6, or -NH-NR 6 R 6'; R 2 is H, halo, -C 1 -C 6 alkyl, or NH 2; R 3 is H, halo, -C 1 -C 6 alkyl, -C 1 -C 6 alkoxy, -C 2 -C 6 alkenyl, or -C 2 -C 6 alkynyl; R 4 is H, -C 1 -C 6 alkyl, -C 1 -C 6 haloalkyl, -C 2 -C 6 alkenyl, or -C 2 -C 6 alkynyl; R 5 is H or -C 1 -C 6 alkyl; R 6 and R 6' are each independently H, C 1 -C 6 alkyl, or -C 1 -C 6 alk-OC 1 -C 6 alkyl; or R 6 and R 6', together with the atom to which they are attached, form a C 2 -C 6 heterocycloalkyl ring or a C 3 -C 6 cycloalkyl ring; R 7 is -C 1 -C 6 alkyl or -C 0 -C 6 alk-C 3 -C 6 cycloalkyl; X is O, S, NH, or N(C 1 -C 6 alkyl), and Y is -(CR 9 R 9') n -, -CR 9 =CR 9' -, C(=O), - C(=O)-(CR 9 R 9') n -, -C(=O)-O-(CR 9 R 9') n -, -CR 9 R 9' -O-, -(CR 9 R 9') n -O-(CR 9 R 9') m -, -(CR 9 R 9') n -NR 10, C(=O)NR 10, or CH-C 1 -C 4 alk-NH 2; or X is -SO 2 - and Y is -(CR 9 R 9') n -, -CR 9 =CR 9' -, -CR 9 R 9' -O-, -(CR 9 R 9') n -O-(CR 9 R 9') m -, -(CR 9 R 9') n -NR 10, or CH-C 1 -C 4 alk-NH 2; wherein n = 1, 2, or 3; m = 1 or 2; each instance of R 9 or R 9 is independently H, D, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halo, -C 1 -C 6 alkoxy, or hydroxy; R 10 is H or C 1 -C 6 alkyl; Z is O, CH 2, or CF 2; and Ar is an optionally substituted 6-membered aryl ring, an optionally substituted 6-membered heteroaryl ring, or an optionally substituted 5-membered heteroaryl ring, wherein the optional substituents on Ar are one or more substituents, independently selected from halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, and C 1 -C 6 haloalkoxy. A is N or C-R 3; R 1 is H, halo, -C 1 -C 6 alkyl, -C 1 -C 6 alkoxy, -C 1 -C 4 haloalkyl, -C 3 -C 6 cycloalkyl, -C 3 -C 6 halocycloalkyl, -C 1 -C 6 alk-O-C 1 -C 6 alkyl, -C 1 -C 6 alk-S -C 1 -C 6 alkyl, - C 1 -C 6 alk-S 2 -C 1 -C 6 alkyl, -CR 6 R 6' CN, -NR 6 R 6', -NHCR 6 R 6' CN, - NHCONR 6 R 6', -NHC OR 7, NHC -C 1 -C 6 alkyl, NHC -C 1 -C 6 haloalkyl, -NH-C 1 -C 6 alk-C -C 1 -C 6 alkyl, -NHC NR 6 R 6', -NH-OR 6, or -NH-NR 6 R 6'; R 2 is H, halo, -C 1 -C 6 alkyl, or NH 2; R 3 is H, halo, -C 1 -C 6 alkyl, -C 1 -C 6 alkoxy, -C 2 -C 6 alkenyl, or -C 2 -C 6 alkynyl; R 4 is H, -C 1 -C 6 alkyl, -C 1 -C 6 haloalkyl, -C 2 -C 6 alkenyl, or -C 2 -C 6 alkynyl; R 5 is H or -C 1 -C 6 alkyl; R 6 and R 6' are each independently H, C 1 -C 6 alkyl, or -C 1 -C 6 alk-OC 1 -C 6 alkyl; or R 6 and R 6', together with the atom to which they are attached, form a C 2 -C 6 heterocycloalkyl ring or a C 3 -C 6 cycloalkyl ring; R 7 is -C 1 -C 6 alkyl or -C 0 -C 6 alk-C 3 -C 6 cycloalkyl; X is O, S, NH, or N(C 1 -C 6 alkyl), and Y is -(CR 9 R 9') n -, -CR 9 =CR 9' -, C(=O), - C(=O)-(CR 9 R 9') n -, -C(=O)-O-(CR 9 R 9') n -, -CR 9 R 9' -O-, -(CR 9 R 9') n -O-(CR 9 R 9') m -, -(CR 9 R 9') n -NR 10, C(=O)NR 10, or CH-C 1 -C 4 alk-NH 2; or X is -SO 2 - and Y is -(CR 9 R 9') n -, -CR 9 =CR 9' -, -CR 9 R 9' -O-, -(CR 9 R 9') n -O-(CR 9 R 9') m -, -(CR 9 R 9') n -NR 10, or CH-C 1 -C 4 alk-NH 2; wherein n = 1, 2, or 3; m = 1 or 2; each instance of R 9 or R 9 is independently H, D, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halo, -C 1 -C 6 alkoxy, or hydroxy; R 10 is H or C 1 -C 6 alkyl; Z is O, CH 2, or CF 2; and Ar is an optionally substituted 6-membered aryl ring, an optionally substituted 6-membered heteroaryl ring, or an optionally substituted 5-membered heteroaryl ring, wherein the optional substituents on Ar are one or more substituents, independently selected from halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, and C 1 -C 6 haloalkoxy.