A compound having the structure of Formula: wherein: Z is a single bond, double bond, -CH 2 -, or -O-; R 1 is aryl or heteroaryl, wherein aryl and heteroaryl are optionally substituted with one or more R 4; R 2 is H, C 1 -C 6 alkyl, C 1 -C 6 alkyl-OR 6, C 1 -C 6 alkylC 3 -C 6 cycloalkyl, C 1 -C 6 alkylC 2 -C 7 heterocycloalkyl, C 1 -C 6 alkyl-CO 2 R 6, optionally substituted C 1 -C 6 alkylaryl, or optionally substituted C 1 -C 6 alkylheteroaryl; R 3 and R 5 are each independently H, or C 1 -C 6 alkyl; or R 3 and R 5 together form an optionally substituted C 3 -C 6 cycloalkyl ring, optionally substituted C 2 -C 7 heterocycloalkyl ring, optionally substituted aryl ring, or an optionally substituted heteroaryl ring; each R 4 is independently selected from F, Cl, Br, I, -CN, -NO 2, -CF 3, -OR 9, -OCF 3, -NR 8 R 9, - C R 10, -CO 2 R 9, -C NR 8 R 9, -N(R 8)C R 10, -N(R 8)CO 2 R 10, -NHS 2 R 10, -S 2 NR 8 R 9, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 haloalkyl, C 2 -C 7 heterocycloalkyl, aryl, and heteroaryl; R 6 is H, or C 1 -C 6 alkyl; R 8 is H, or C 1 -C 6 alkyl; R 9 is H, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 2 -C 7 heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkylaryl, or C 1 -C 6 alkylheteroaryl; R 10 is C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 2 -C 7 heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkylaryl, or C 1 -C 6 alkylheteroaryl; R 11 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 2 -C 7 heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkylC 3 -C 6 cycloalkyl, C 1 -C 6 alkylaryl, or C 1 -C 6 alkylheteroaryl; R 12 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 2 -C 7 heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkylC 3 -C 6 cycloalkyl, C 1 -C 6 alkylaryl, or C 1 -C 6 alkylheteroaryl; or R 11 and R 12 together with the nitrogen to which they are attached form an optionally substituted C 2 -C 7 heterocycloalkyl ring; and R 13 and R 14 are each independently H, or C 1 -C 6 alkyl; or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate, or pharmaceutically acceptable salt hydrate thereof. Z is a single bond, double bond, -CH 2 -, or -O-; R 1 is aryl or heteroaryl, wherein aryl and heteroaryl are optionally substituted with one or more R 4; R 2 is H, C 1 -C 6 alkyl, C 1 -C 6 alkyl-OR 6, C 1 -C 6 alkylC 3 -C 6 cycloalkyl, C 1 -C 6 alkylC 2 -C 7 heterocycloalkyl, C 1 -C 6 alkyl-CO 2 R 6, optionally substituted C 1 -C 6 alkylaryl, or optionally substituted C 1 -C 6 alkylheteroaryl; R 3 and R 5 are each independently H, or C 1 -C 6 alkyl; or R 3 and R 5 together form an optionally substituted C 3 -C 6 cycloalkyl ring, optionally substituted C 2 -C 7 heterocycloalkyl ring, optionally substituted aryl ring, or an optionally substituted heteroaryl ring; each R 4 is independently selected from F, Cl, Br, I, -CN, -NO 2, -CF 3, -OR 9, -OCF 3, -NR 8 R 9, - C R 10, -CO 2 R 9, -C NR 8 R 9, -N(R 8)C R 10, -N(R 8)CO 2 R 10, -NHS 2 R 10, -S 2 NR 8 R 9, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 haloalkyl, C 2 -C 7 heterocycloalkyl, aryl, and heteroaryl; R 6 is H, or C 1 -C 6 alkyl; R 8 is H, or C 1 -C 6 alkyl; R 9 is H, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 2 -C 7 heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkylaryl, or C 1 -C 6 alkylheteroaryl; R 10 is C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 2 -C 7 heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkylaryl, or C 1 -C 6 alkylheteroaryl; R 11 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 2 -C 7 heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkylC 3 -C 6 cycloalkyl, C 1 -C 6 alkylaryl, or C 1 -C 6 alkylheteroaryl; R 12 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 2 -C 7 heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 alkylC 3 -C 6 cycloalkyl, C 1 -C 6 alkylaryl, or C 1 -C 6 alkylheteroaryl; or R 11 and R 12 together with the nitrogen to which they are attached form an optionally substituted C 2 -C 7 heterocycloalkyl ring; and R 13 and R 14 are each independently H, or C 1 -C 6 alkyl;