A compound of Formula or a pharmaceutically acceptable salt thereof, wherein: A is S or O; R 1 is C 2 -C 10 hydroxyalkyl, optionally substituted with 1-3 R 5; R 2 is H, C 1 -C 6 alkyl, C 1 -C 6 hydroxyalkyl, C 3 -C 10 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or C 1 -C 6 alkoxy; R 3 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 acyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkoxy, C 4 -C 10 cycloalkyloxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, hydroxyl, alkylthio, thionyl, sulfonyl, sulfonamidyl, C 6 -C 12 aryl, 5-14-membered heteroaryl, C 6 -C 12 aryl-C 1 -C 6 alkyl, 5-14-membered heteroaryl-C 1 -C 6 alkyl, C 6 -C 12 aryloxy, -O-C 6 -C 12 aryl-C 1 -C 6 alkyl, -O-C 1 -C 6 alkyl-C 6 -C 12 aryl, -C 6 -C 12 aryl-C 1 -C 6 alky-O, 5-14-membered heteroaryloxy, 3-18-membered heterocycloalkyl, amino, C 1 -C 6 alkylamino, C 2 -C 12 dialkylamino, -C NH-, -C N-C 1 -C 6 alkyl-, -NHC -, -N- C 1 -C 6 alkyl C -, urea, sulfonylurea, nitro, cyano, each of which is optionally substituted with 1-4 R 5; R 4 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 acyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkoxy, C 4 -C 10 cycloalkyloxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, hydroxyl, alkylthio, thionyl, sulfonyl, sulfonamidyl, C 6 -C 12 aryl, 5-14-membered heteroaryl, C 6 -C 12 aryl-C 1 -C 6 alkyl, 5-14-membered heteroaryl-C 1 -C 6 alkyl, C 6 -C 12 aryloxy, -O-C 6 -C 12 aryl-C 1 -C 6 alkyl, -O-C 1 -C 6 alkyl-C 6 -C 12 aryl, -C 6 -C 12 aryl-C 1 -C 6 alky-O, 5-14-membered heteroaryl-C 1 -C 6 alkyl, 5-14-membered heteroaryloxy, 3-18-membered heterocycloalkyl, amino, C 1 -C 6 alkylamino, C 2 -C 12 dialkylamino, -C NH-, -C N-C 1 -C 6 alkyl-,-NHC -, -N-C 1 -C 6 alkyl C -, urea, sulfonylurea, nitro, cyano, each of which is optionally substituted with 1-4 R 5; each R 5 is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 acyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkoxy, C 4 -C 10 cycloalkyloxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, hydroxyl, alkylthio, thionyl, sulfonyl, sulfonamidyl, amino, C 1 -C 6 alkylamino, C 2 -C 12 dialkylamino, keto, -C NH-, -C N-C 1 -C 6 alkyl-,-NHC -, -N-C 1 -C 6 alkyl C -, urea, sulfonylurea, nitro, cyano, each of which is optionally substituted with 1-5 R 6; and each R 6 is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 acyl, C 1 -C 6 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, hydroxyl, amino, -C NH-, -C N-C 1 -C 6 alkyl-, -NHC -, -N-C 1 -C 6 alkyl C -, nitro, or cyano. A is S or O; R 1 is C 2 -C 10 hydroxyalkyl, optionally substituted with 1-3 R 5; R 2 is H, C 1 -C 6 alkyl, C 1 -C 6 hydroxyalkyl, C 3 -C 10 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or C 1 -C 6 alkoxy; R 3 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 acyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkoxy, C 4 -C 10 cycloalkyloxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, hydroxyl, alkylthio, thionyl, sulfonyl, sulfonamidyl, C 6 -C 12 aryl, 5-14-membered heteroaryl, C 6 -C 12 aryl-C 1 -C 6 alkyl, 5-14-membered heteroaryl-C 1 -C 6 alkyl, C 6 -C 12 aryloxy, -O-C 6 -C 12 aryl-C 1 -C 6 alkyl, -O-C 1 -C 6 alkyl-C 6 -C 12 aryl, -C 6 -C 12 aryl-C 1 -C 6 alky-O, 5-14-membered heteroaryloxy, 3-18-membered heterocycloalkyl, amino, C 1 -C 6 alkylamino, C 2 -C 12 dialkylamino, -C NH-, -C N-C 1 -C 6 alkyl-, -NHC -, -N- C 1 -C 6 alkyl C -, urea, sulfonylurea, nitro, cyano, each of which is optionally substituted with 1-4 R 5; R 4 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 acyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkoxy, C 4 -C 10 cycloalkyloxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, hydroxyl, alkylthio, thionyl, sulfonyl, sulfonamidyl, C 6 -C 12 aryl, 5-14-membered heteroaryl, C 6 -C 12 aryl-C 1 -C 6 alkyl, 5-14-membered heteroaryl-C 1 -C 6 alkyl, C 6 -C 12 aryloxy, -O-C 6 -C 12 aryl-C 1 -C 6 alkyl, -O-C 1 -C 6 alkyl-C 6 -C 12 aryl, -C 6 -C 12 aryl-C 1 -C 6 alky-O, 5-14-membered heteroaryl-C 1 -C 6 alkyl, 5-14-membered heteroaryloxy, 3-18-membered heterocycloalkyl, amino, C 1 -C 6 alkylamino, C 2 -C 12 dialkylamino, -C NH-, -C N-C 1 -C 6 alkyl-,-NHC -, -N-C 1 -C 6 alkyl C -, urea, sulfonylurea, nitro, cyano, each of which is optionally substituted with 1-4 R 5; each R 5 is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 acyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkoxy, C 4 -C 10 cycloalkyloxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, hydroxyl, alkylthio, thionyl, sulfonyl, sulfonamidyl, amino, C 1 -C 6 alkylamino, C 2 -C 12 dialkylamino, keto, -C NH-, -C N-C 1 -C 6 alkyl-,-NHC -, -N-C 1 -C 6 alkyl C -, urea, sulfonylurea, nitro, cyano, each of which is optionally substituted with 1-5 R 6; and each R 6 is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 acyl, C 1 -C 6 alkoxy, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, hydroxyl, amino, -C NH-, -C N-C 1 -C 6 alkyl-, -NHC -, -N-C 1 -C 6 alkyl C -, nitro, or cyano.