A compound having a structure according to Formula: or a salt or solvate thereof, wherein: A is a ring selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted 5- or 6-membered heterocycloalkyl, and substituted or unsubstituted 5-or 6-membered heteroaryl; E 1 is N or CR 5, wherein R 5 is selected from the group consisting of H, OH, unsubstituted C 1 -C 3 alkoxy, unsubstituted C 1 -C 3 alkyl, unsubstituted C 2 -C 3 alkenyl, unsubstituted C 2 -C 3 alkynyl, C 1 -C 3 haloalkyl and halogen; E 2 is N or CR 5a, wherein R 5a is selected from the group consisting of H, unsubstituted C 1 -C 4 alkyl, halogen and CN; R 1 is selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted acyl; R 2 is selected from the group consisting of H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 6 alkenyl, substituted or unsubstituted C 2 -C 6 alkynyl, substituted or unsubstituted 3- to 6-membered heteroalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, and substituted or unsubstituted 3- to 6-membered heterocycloalkyl; R 3 is selected from the group consisting of substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 6 alkenyl, substituted or unsubstituted C 2 -C 6 alkynyl, substituted or unsubstituted 3- to 6-membered heteroalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, and substituted or unsubstituted 3- to 6-membered heterocycloalkyl; or R 2 and R 3, together with the carbon atom to which they are attached, are optionally joined to form a substituted or unsubstituted C 3 -C 6 cycloalkyl or a substituted or unsubstituted 3- to 6-membered heterocycloallcyl; R 4 is selected from the group consisting of substituted or unsusbtituted C 1 -C 10 alkyl, substituted or unsubstituted C 2 -C 10 alkenyl, substituted or unsubstituted C 2 -C 10 alkynyl, substituted or unsubstituted 3- to 10-membered heteroalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted 3- to 8-membered heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and -NR 25 R 26; or R 4 and R 3, together with the atoms to which they are attached, are optionally joined to form a substituted or unsubstituted saturated 3- to 8-membered heterocyclic ring; or R 4, R 2 and R 3, together with the atoms to which they are attached, are optionally joined to form a substituted or unsubstituted heterocyclic bicyclic ring system of fused 4- to 8-membered rings; and R 25 and R 26 are independently H, substituted or unsubstituted C 3 -C 8 cycloalkyl, or substituted or unsubstituted C 1 -C 10 alkyl. A is a ring selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted 5- or 6-membered heterocycloalkyl, and substituted or unsubstituted 5-or 6-membered heteroaryl; E 1 is N or CR 5, wherein R 5 is selected from the group consisting of H, OH, unsubstituted C 1 -C 3 alkoxy, unsubstituted C 1 -C 3 alkyl, unsubstituted C 2 -C 3 alkenyl, unsubstituted C 2 -C 3 alkynyl, C 1 -C 3 haloalkyl and halogen; E 2 is N or CR 5a, wherein R 5a is selected from the group consisting of H, unsubstituted C 1 -C 4 alkyl, halogen and CN; R 1 is selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted acyl; R 2 is selected from the group consisting of H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 6 alkenyl, substituted or unsubstituted C 2 -C 6 alkynyl, substituted or unsubstituted 3- to 6-membered heteroalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, and substituted or unsubstituted 3- to 6-membered heterocycloalkyl; R 3 is selected from the group consisting of substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 6 alkenyl, substituted or unsubstituted C 2 -C 6 alkynyl, substituted or unsubstituted 3- to 6-membered heteroalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, and substituted or unsubstituted 3- to 6-membered heterocycloalkyl; or R 2 and R 3, together with the carbon atom to which they are attached, are optionally joined to form a substituted or unsubstituted C 3 -C 6 cycloalkyl or a substituted or unsubstituted 3- to 6-membered heterocycloallcyl; R 4 is selected from the group consisting of substituted or unsusbtituted C 1 -C 10 alkyl, substituted or unsubstituted C 2 -C 10 alkenyl, substituted or unsubstituted C 2 -C 10 alkynyl, substituted or unsubstituted 3- to 10-membered heteroalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted 3- to 8-membered heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and -NR 25 R 26; or R 4 and R 3, together with the atoms to which they are attached, are optionally joined to form a substituted or unsubstituted saturated 3- to 8-membered heterocyclic ring; or R 4, R 2 and R 3, together with the atoms to which they are attached, are optionally joined to form a substituted or unsubstituted heterocyclic bicyclic ring system of fused 4- to 8-membered rings; and R 25 and R 26 are independently H, substituted or unsubstituted C 3 -C 8 cycloalkyl, or substituted or unsubstituted C 1 -C 10 alkyl.