A compound having structural Formula I: or a salt thereof, wherein: X 1 is selected from C and N; X 2 is selected from C and N; exactly one of X 1 and X 2 is N; X 3 is N; X 4 and X 5 are C; X 1, X 2, X 3, X 4, and X 5 form a five membered heteroaryl; R 1 is selected from C 1-8 alkyl, C 3-12 cycloalkyl, and C 3-7 heterocycloalkyl, any of which is optionally substituted with one to three R 5 groups; R 2 is H or is selected from C 1-8 alkyl, amino, aryl, C 5-7 cycloalkyl, C 1-8 haloalkyl, C 1-8 heteroalkyl, C 5-7 heteroaryl, C 3-7 heterocycloalkyl, and C 1-8 sulfonylalkyl, any of which is optionally substituted with one to three R 6 groups; R 3 is selected from H, C 1-8 alkyl, (C 1-8 alkoxy) C 1-8 alkyl, (arylalkoxy) C 1-8 alkyl, (C 5-7 heteroarylalkoxy) C 1-8 alkyl, cyano, C 5-7 cycloalkyl, halo, C 1-8 haloalkoxy, and C 1-8 haloalkyl; R 4 is N(R 4a) 2, wherein each R 4a is independently selected from hydrogen, C 1-4 alkyl, and C 1-4 haloalkyl; or R 3 and R 4 together with the atoms to which they are attached form a 5- or 6-membered heteroaryl or heteroalkyl ring, optionally substituted with one to three R 7 groups; each R 5 and R 6 is independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-4 alkylthio, C 1-4 haloalkylthio, aryl, C 5-7 heteroaryl, C 3-7 cycloalkyl, C 3-7 heterocycloalkyl, (aryl)C 1-4 alkyl, (C 5-7 heteroaryl)C 1-4 alkyl, (C 3-7 cycloalkyl)C 1-4 alkyl, (C 3-7 heterocycloalkyl)C 1-4 alkyl, (ethenyl)C 1-4 alkyl, (ethynyl)C 1-4 alkyl, (aryl)C 1-4 alkoxy, (C 5-7 heteroaryl)C 1-4 alkoxy, (C 3-7 cycloalkyl)C 1-4 alkoxy, (C 3-7 heterocycloalkyl)C 1-4 alkoxy, (aryl)C 1-4 alkylthio, (heteroaryl)C 1-4 alkylthio, (C 3-7 cycloalkyl)C 1-4 alkylthio, (C 3-7 heterocycloalkyl)C 1-4 alkylthio, amino, halo, hydroxy, cyano, and oxo; and each R 7 is independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, aryl, C 5-7 heteroaryl, C 3-7 cycloalkyl, C 3-7 heterocycloalkyl, (aryl)C 1-4 alkyl, (C 5-7 heteroaryl)C 1-4 alkyl, (C 3-7 cycloalkyl)C 1-4 alkyl, (C 3-7 heterocycloalkyl)C 1-4 alkyl, halo, hydroxy, cyano, and oxo. X 1 is selected from C and N; X 2 is selected from C and N; exactly one of X 1 and X 2 is N; X 3 is N; X 4 and X 5 are C; X 1, X 2, X 3, X 4, and X 5 form a five membered heteroaryl; R 1 is selected from C 1-8 alkyl, C 3-12 cycloalkyl, and C 3-7 heterocycloalkyl, any of which is optionally substituted with one to three R 5 groups; R 2 is H or is selected from C 1-8 alkyl, amino, aryl, C 5-7 cycloalkyl, C 1-8 haloalkyl, C 1-8 heteroalkyl, C 5-7 heteroaryl, C 3-7 heterocycloalkyl, and C 1-8 sulfonylalkyl, any of which is optionally substituted with one to three R 6 groups; R 3 is selected from H, C 1-8 alkyl, (C 1-8 alkoxy) C 1-8 alkyl, (arylalkoxy) C 1-8 alkyl, (C 5-7 heteroarylalkoxy) C 1-8 alkyl, cyano, C 5-7 cycloalkyl, halo, C 1-8 haloalkoxy, and C 1-8 haloalkyl; R 4 is N(R 4a) 2, wherein each R 4a is independently selected from hydrogen, C 1-4 alkyl, and C 1-4 haloalkyl; or R 3 and R 4 together with the atoms to which they are attached form a 5- or 6-membered heteroaryl or heteroalkyl ring, optionally substituted with one to three R 7 groups; each R 5 and R 6 is independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-4 alkylthio, C 1-4 haloalkylthio, aryl, C 5-7 heteroaryl, C 3-7 cycloalkyl, C 3-7 heterocycloalkyl, (aryl)C 1-4 alkyl, (C 5-7 heteroaryl)C 1-4 alkyl, (C 3-7 cycloalkyl)C 1-4 alkyl, (C 3-7 heterocycloalkyl)C 1-4 alkyl, (ethenyl)C 1-4 alkyl, (ethynyl)C 1-4 alkyl, (aryl)C 1-4 alkoxy, (C 5-7 heteroaryl)C 1-4 alkoxy, (C 3-7 cycloalkyl)C 1-4 alkoxy, (C 3-7 heterocycloalkyl)C 1-4 alkoxy, (aryl)C 1-4 alkylthio, (heteroaryl)C 1-4 alkylthio, (C 3-7 cycloalkyl)C 1-4 alkylthio, (C 3-7 heterocycloalkyl)C 1-4 alkylthio, amino, halo, hydroxy, cyano, and oxo; and each R 7 is independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, aryl, C 5-7 heteroaryl, C 3-7 cycloalkyl, C 3-7 heterocycloalkyl, (aryl)C 1-4 alkyl, (C 5-7 heteroaryl)C 1-4 alkyl, (C 3-7 cycloalkyl)C 1-4 alkyl, (C 3-7 heterocycloalkyl)C 1-4 alkyl, halo, hydroxy, cyano, and oxo.