n is independently, at each instance, 0, 1 or 2;

R¹ is

R² is, independently, in each instance, R¹⁰, C_1-8alkyl substituted by 0, 1 or 2 substituents selected from R¹⁰, —(CH₂)_nphenyl substituted by 0, 1, 2 or 3 substituents independently selected from R¹⁰, or a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R¹⁰;

R³ is, independently, in each instance, H, halo, —NHC_1-3alkyl, —N(C_1-3alkyl)C_1-3alkyl, or C_1-3alkyl; wherein, at least one of R² and R³ is other than H;

R⁴ is

R⁵ is independently, at each instance, R^f, R^g, halo, nitro, cyano, —OR^e, —OR^g, —OC_2-6alkylNR^aR^f, —OC_2-6alkylOR^f, —NR^aR^f, —NR^aR^g, —NR^fC_2-6alkylNR^aR^f, —NR^fC_2-6alkylOR^f, naphthyl, —CO₂R^e, —C(═O)R^e, —C(═O)NR^aR^f, —C(═O)NR^aR^g, —NR^fC(═O)R^e, —NR^fC(═O)R^g, —NR^fC(═O)NR^aR^f, —NR^fCO₂R^e, —C_1-8alkylOR^f, —C_1-6alkylNR^aR^f, —S(═O)_nR^e, —S(═O)₂NR^aR^f, —NR^aS(═O)₂R^e, —C(═O)NR^aR^f, a phenyl ring substituted with 0, 1, 2, or 3 substituents independently selected from R¹⁰; or R⁵ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 atoms selected from O, N and S, substituted with 0, 1, 2, or 3 substituents independently selected from R¹⁰;

R⁶ is independently, at each instance, H, C_1-5alkyl, C_1-4haloalkyl, halo, —OC_1-6alkyl, —OC_1-4haloalkyl, —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —NR^aR^a, —NR^aC_1-4haloalkyl, —NR^aC_2-6alkylNR^aR^a or —NR^aC_2-6alkylOR^a, —C_1-8alkylOR^a, —C_1-6alkylNR^aR^a, —S(C_1-6alkyl), a phenyl ring substituted with 1, 2, or 3 substituents independently selected from R¹⁰; or R⁶ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 atoms selected from O, N and S substituted with 0, 1, 2, or 3 substituents independently selected from R¹⁰;

R⁷ is independently, at each instance, H, acyclicC_1-8alkyl, C_1-4haloalkyl, halo, —OC_1-6alkyl, —OC_1-4haloalkyl, —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —NR^aR^a, —NR^aC_1-4haloalkyl, —NR^aC_2-6alkylNR^aR^a, —NR^aC_2-6alkylOR^a, —C_1-8alkylOR^a, —C_1-6alkylNR^aR^a or —S(C_1-6alkyl); or R⁷ is a saturated or unsaturated 4- or 5-membered ring heterocycle containing a single nitrogen atom, wherein the ring is substituted with 0, 1 or 2 substituents independently selected from halo, C_1-2haloalkyl and C_1-3alkyl;

R⁸ is independently, at each instance, H, C_1-5alkyl, C_1-4haloalkyl, halo, —OC_1-6alkyl, —OC_1-4haloalkyl, —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —NR^aR^a, —NR^aC_1-4haloalkyl, —NR^aC_2-6alkylNR^aR^a, —NR^aC_2-6alkylOR^a, —C_1-8alkylOR^a, —C_1-6alkylNR^aR^a, —S(C_1-6alkyl), a phenyl ring substituted with 1, 2, or 3 substituents independently selected from R¹⁰, or R⁸ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 atoms selected from O, N and S substituted with 0, 1, 2, or 3 substituents independently selected from R¹⁰;

R⁹ is independently, at each instance, R^f, R^g, halo, nitro, cyano, —OR^e, —OR^g, —OC_2-6alkylNR^aR^f, —OC_2-6alkylOR^f, —NR^aR^f, —NR^aR^g, —NR^fC_2-6 alkylNR^aR^f, —NR^fC_2-6alkylOR^f, naphthyl, —CO₂R^e, —C(═O)R^e, —C(═O)NR^aR^f, —C(═O)NR^aR^g, —NR^fC(═O)R^e, —NR^fC(═O)R^g, —NR^fC(═O)NR^aR^f, —NR^fCO₂R^e, —C_1-8alkylOR^f, —C_1-6alkylNR^aR^f, —S(═O)_nR^e, —S(═O)₂NR^aR^f, —NR^aS(═O)₂R^e, —OC(═O)NR^aR^f, a phenyl ring substituted with 0, 1, 2, or 3 substituents independently selected from R¹⁰; or R⁹ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 atoms selected from O, N and S substituted with 0, 1, 2, or 3 substituents independently selected from R¹⁰; or R⁹ is a saturated or unsaturated 4- or 5-membered ring heterocycle containing a single nitrogen atom, wherein the ring is substituted with 0, 1 or 2 substituents independently selected from halo, C_1-2haloalkyl and C_1-3alkyl; wherein at least one of R⁵, R⁶, R⁷, R⁸ and R⁹ is C_1-8alkyl, C_1-4haloalkyl, halo, —OC_1-4haloalkyl, —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —NR^aC_1-4haloalkyl, —NR^aC_2-6alkylNR^aR^a, —NR^aC_2-6alkylOR^a, —C_1-8alkylOR^a, —C_1-6alkylNR^aR^a or —S(C_1-6alkyl); and

R¹¹ and R¹² together are a saturated or un satureated 3- or 4-atom bridge containing 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not graeter than 2, wherein the bridge is substituted by 0,1 or 2 substituted selected from ═O, R^e, halo, cyano, nitro —C(═O)R^e, —C(═O)OR^e, —C(═O)NR^aR^f, —C(═NR^a)NR^aR^f, —OR^f, —OC(═O)R^e, —OC(═O)NR^aR^f, —OC(═O)N(R^f)S(═O)₂R^e, —OC_2-6alkylNR^aR^f, —OC_2-6alkylOR^f, —SR^f, —S(═O)R^e, —S(═O)₂R^e, —S(═O)₂NR^aR^f, —S(═O)₂N(R^f)C(═O)R^e, —S(═O)₂N(R^f)C(═O)OR^e, —S(═O)₂N(R^f)C(═O)NR^aR^f, —NR^aR^f, —N(R^f)C(═O)R^e, —N(R^f)C(═O)OR^e, —N(R^f)C(═O)NR^aR^f, —N(R^f)C(═NR^a)NR^aR^f, —N(R^f)S(═O)₂R^e, —N(R^f)S(═O)₂NR^aR^f, —NR^fC_2-6alkylNR^aR^f and —NR^fC_2-6alkylOR^f; wherin when R³ is NH₂, then —R¹¹—R¹²— is not —C═C—C═N— or any substituted version thereof; or

R¹² is independently, at each instance, selected from H, C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —C(═O)(C_1-8alkyl), —C(═O)O(C_1-8alkyl), —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)(C_1-8alkyl), —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂(C_1-8alkyl), —OC_2-6alkyNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)(C_1-8alkyl), —S(═O)₂(C_1-8alkyl), —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)(C_1-8-alkyl), —S(═O)₂N(R^a)C(═O)O(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)NR^aR^a, —N(R^a)C(═O)(C_1-8alkyl), —N(R^a)C(═O)O(C_1-8alkyl), —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂(C_1-8alkyl), —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^a and —NR^aC_2-6alkylOR^a; or R¹² is a saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 1, 2 or 3 atoms selected from N, O and S, wherein the ring is fused with 0 or 1 benzo groups and 0 or 1 saturated or unsaturated 5-, 6- or 7-membered heterocyclic ring containing 1, 2 or 3 atoms selected from N, O and S; wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groups selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —C(═O)(C_1-8alkyl), —C(═O)O(C_1-8alkyl), —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)(C_1-8alkyl), —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂(C_1-8alkyl), —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)(C_1-8alkyl), —S(═O)₂(C_1-8alkyl), —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)O(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)(C_1-8alkyl) —N(R^a)C(═O)O(C_1-8alkyl), —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂(C_1-8alkyl), —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^a and —NR^aC_2-6alkylOR^a; or R¹² is C_1-4alkyl substituted by 0, 1, 2 or 3 groups selected from C_1-4haloalkyl, halo, cyano, nitro, —C(═O)(C_1-8alkyl), —C(═O)O(C_1-8alkyl), —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)(C_1-8alkyl), —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂(C_1-8alkyl), —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)(C_1-8alkyl), —S(═O)₂(C_1-8alkyl), —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)O(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)(C_1-8alkyl), —N(R^a)C(═O)O(C_1-8alkyl), —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂(C_1-8alkyl), —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^a and —NR^aC_2-6alkylOR^a;

R¹³ is independently, at each instance, selected from H, C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —C(═O)(C_1-8alkyl), —C(═O)O(C_1-8alkyl), —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)(C_1-8alkyl), —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂(C_1-8alkyl), —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)(C_1-8alkyl), —S(═O)₂(C_1-8alkyl), —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)O(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)(C_1-8alkyl), —N(R^a)C(═O)O(C_1-8alkyl), —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂(C_1-8alkyl), —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^a and —NR^aC_2-6alkylOR^a; or R¹³ is a saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 1, 2 or 3 atoms selected from N, O and S, wherein the ring is fused with 0 or 1 benzo groups and 0 or 1 saturated or unsaturated 5-, 6- or 7-membered heterocyclic ring containing 1, 2 or 3 atoms selected from N, O and S; wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groups selected from C_1-8alkyl, C_1-4-haloalkyl, halo, cyano, nitro, —C(═O)(C_1-8alkyl), —C(═O)O(C_1-8alkyl), —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)(C_1-8alkyl), —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂(C_1-8alkyl), —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)(C_1-8alkyl), —S(═O)₂(C_1-8alkyl), —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)O(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)(C_1-8alkyl), —N(R^a)C(═O)O(C_1-8alkyl), —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂(C_1-8alkyl), —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^a and —NR^aC_2-6alkylOR^a; or R¹³ is C_1-4alkyl substituted by 0, 1, 2 or 3 groups selected from C_1-4haloalkyl, halo, cyano, nitro, —C(═O)(C_1-8alkyl), —C(═O)O(C_1-8alkyl), —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)(C_1-8alkyl), —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂(C_1-8alkyl), —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)(C_1-8alkyl), —S(═O)₂(C_1-8alkyl), —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)O(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)(C_1-8alkyl), —N(R^a)C(═O)O(C_1-8alkyl), —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂(C_1-8alkyl), —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^a and —NR^aC_2-6alkylOR^a;

R¹⁴ is independently, at each instance, selected from H, C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —C(═O)(C_1-8alkyl), —C(═O)O(C_1-8alkyl), —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)(C_1-8alkyl), —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂(C_1-8alkyl), —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)(C_1-8alkyl), —S(═O)₂(C_1-8alkyl), —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)O(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)(C_1-8alkyl), —N(R^a)C(═O)O(C₈alkyl), —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂(C_1-8alkyl), —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^a and —NR^aC_2-6alkylOR^a; or R¹⁴ is a saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 1, 2 or 3 atoms selected from N, O and S, wherein the ring is fused with 0 or 1 benzo groups and 0 or 1 saturated or unsaturated 5-, 6- or 7-membered heterocyclic ring containing 1, 2 or 3 atoms selected from N, O and S; wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groups selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —C(═O)(C_1-8alkyl), —C(═O)O(C_1-8alkyl), —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)(C_1-8alkyl), —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂(C_1-8alkyl), —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)(C_1-8alkyl), —S(═O)₂(C_1-8alkyl), —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)O(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)(C_1-8alkyl), —N(R^a)C(═O)O(C_1-8alkyl), —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂(C_1-8alkyl), —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^a and —NR^aC_2-6alkylOR^a; or R¹⁴ is C_1-4alkyl substituted by 0, 1, 2 or 3 groups selected from C_1-4haloalkyl, halo, cyano, nitro, —C(═O)(C_1-8alkyl), —C(═O)O(C 18alkyl), —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)(C_1-8alkyl), —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂(C_1-8alkyl), —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)(C_1-8alkyl), —S(═O)₂(C_1-8alkyl), —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)O(C_1-8alkyl), —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)(C_1-8alkyl), —N(R^a)C(═O)O(C_1-8alkyl), —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂(C_1-8alkyl), —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^a and —NR^aC_2-6alkylOR^a; wherein at least one of R¹⁰, R¹¹, R¹², R¹³ and R¹⁴ is other than H;

R^a is independently, at each instance, H, phenyl, benzyl or C_1-6alkyl;

R^b is a heterocycle selected from the group of thiophene, pyrrole, 1,3-oxazole, 1,3-thiazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, 1,2,3-oxadiazole, 1,2,3-thiadiazole, 1H-1,2,3-triazole, isothiazole, 1,2,4-oxadiazole, 1,2,4-thiadiazole, 1,2,3,4-oxatriazole, 1,2,3,4-thiatriazole, 1H-1,2,3,4-tetraazole, 1,2,3,5-oxatriazole, 1,2,3,5-thiatriazole, imidazol-1-yl, imidazol-4-yl, 1,2,4-triazol-4-yl, 1,2,4-triazol-5-yl, thiolane, pyrrolidine, tetrahydrofuran, 4,5-dihydrothiophene, 2-pyrroline, 4,5-dihydrofuran, pyridazine, pyrimidine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,2,4-triazine, 1,3,5-triazine, pyridine, 2H-3,4,5,6-tetrahydropyran, thiane, 1,2-diazaperhydroine, 1,3-diazaperhydroine, piperazine, 1,3-oxazaperhydroine, morpholine, 1,3-thiazaperhydroine, 1,4-thiazaperhydroine, piperidine, 2H-3,4-dihydropyran, 2,3-dihydro-4H-thiin, 1,4,5,6-tetrahydropyridine, 2H-5,6-dihydropyran, 2,3-dihydro-6H-thiin, 1,2,5,6-tetrahydropyridine, 3,4,5,6-tetrahydropyridine, 4H-pyran, 4H-thiin, 1,4-dihydropyridine, 1,4-dithiane, 1,4-dioxane, 1,4-oxathiane, 1,2-oxazolidine, 1,2-thiazolidine, pyrazolidine, 1,3-oxazolidine, 1,3-thiazolidine, imidazolidine, 1,2,4-oxadiazolidine, 1,3,4-oxadiazolidine, 1,2,4-thiadiazolidine, 1,3,4-thiadiazolidine, 1,2,4-triazolidine, 2-imidazoline, 3-imidazoline, 2-pyrazoline, 4-imidazoline, 2,3-dihydroisothiazole, 4,5-dihydroisoxazole, 4,5-dihydroisothiazole, 2,5-dihydroisoxazole, 2,5-dihydroisothiazole, 2,3-dihydroisoxazole, 4,5-dihydrooxazole, 2,3-dihydrooxazole, 2,5-dihydrooxazole, 4,5-dihydrothiazole, 2,3-dihydrothiazole, 2,5-dihydrothiazole, 1,3,4-oxathiazolidine, 1,4,2-oxathiazolidine, 2,3-dihydro-1H-[1,2,3]triazole, 2,5-dihydro-1H-[1,2,3]triazole, 4,5-dihydro-1H-[1,2,3]triazole, 2,3-dihydro-1H-[1,2,4]triazole, 4,5-dihydro-1H-[1,2,4]triazole, 2,3-dihydro-[1,2,4]oxadiazole, 2,5-dihydro-[1,2,4]oxadiazole, 4,5-dihydro-[1,2,4]thiadiazole, 2,3-dihydro-[1,2,4] thidiazole, 2,5-dihydro-[1,2,4] thiadiazole, 4,5-dihydro-[1,2,4]thiadiazole, 2,5-dihydro-[1,2,4]oxadiazole, 2,3-dihydro-[1,2,4]oxadiazole, 4,5-dihydro-[1,2,4]oxadiazole, 2,5-dihydro-[1,2,4]thiadiazole, 2,3-dihydro-[1,2,4]thiadiazole, 4,5-dihydro-[1,2,4] thiadiazole, 2,3-dihydro-[1,3,4]oxadiazole, 2,3-dihydro-[1,3,4]thiadiazole, [1,4,2]oxathiazole, [1,3,4]oxathiazole, 1,3,5-triazaperhydroine, 1,2,4-triazaperhydroine, 1,4,2-dithiazaperhydroine, 1,4,2-dioxazaperhydroine, 1,3,5-oxadiazaperhydroine, 1,2,5-oxadiazaperhydroine, 1,3,4-thiadiazaperhydroine, 1,3,5-thiadiazaperhydroine, 1,2,5-thiadiazaperhydroine, 1,3,4-oxadiazaperhydroine, 1,4,3-oxathiazaperhydroine, 1,4,2-oxathiazaperhydroine, 1,4,5,6-tetrahydropyridazine, 1,2,3,4-tetrahydropyridazine, 1,2,3,6-tetrahydropyridazine, 1,2,5,6-tetrahydropyrimidine, 1,2,3,4-tetrahydropyrimidine, 1,4,5,6-tetrahydropyrimidine, 1,2,3,6-tetrahydropyrazine, 1,2,3,4-tetrahydropyrazine, 5,6-dihydro-4H-[1,2]oxazine, 5,6-dihydro-2H-[1,2]oxazine, 3,6-dihydro-2H-[1,2]oxazine, 3,4-dihydro-2H-[1,2]oxazine, 5,6-dihydro-4H-[1,2]thiazine, 5,6-dihydro-2H-[1,2] thiazine, 3,6-dihydro-2H-[1,2] thiazine, 3,4-dihydro-2H-[1,2]thiazine, 5,6-dihydro-2H-[1,3]oxazine, 5,6-dihydro-4H-[1,3]oxazine, 3,6-dihydro-2H-[1,3]oxazine, 3,4-dihydro-2H-[1,3]oxazine, 3,6-dihydro-2H-[1,4]oxazine, 3,4-dihydro-2H-[1,4]oxazine, 5,6-dihydro-2H-[1,3]thiazine, 5,6-dihydro-4H-[1,3]thiazine, 3,6-dihydro-2H-[1,3]thiazine, 3,4-dihydro-2H-[1,3]thiazine, 3,6-dihydro-2H-[1,4]thiazine, 3,4-dihydro-2H-[1,4]thiazine, 1,2,3,6-tetrahydro-[1,2,4]triazine, 1,2,3,4-tetrahydro-[1,2,4]triazine, 1,2,3,4-tetrahydro-[1,3,5]triazine, 2,3,4,5-tetrahydro-[1,2,4]triazine, 1,4,5,6-tetrahydro-[1,2,4]triazine, 5,6-dihydro-[1,4,2]dioxazine, 5,6-dihydro-[1,4,2]dioxazine, 5,6-dihydro-[1,4,2]dithiazine, 2,3-dihydro-[1,4,2]dioxazine, 3,4-dihydro-2H-[1,3,4]oxadiazine, 3,6-dihydro-2H-[1,3,4]oxadiazine, 3,4-dihydro-2H-[1,3,5]oxadiazine, 3,6-dihydro-2H-[1,3,5]oxadiazine, 5,6-dihydro-2H-[1,2,5]oxadiazine, 5,6-dihydro-4H-[1,2,5]oxadiazine, 3,4-dihydro-2H-[1,3,4]thiadiazine, 3,6-dihydro-2H-[1,3,4]thiadiazine, 3,4-dihydro-2H-[1,3,5]thiadiazine, 3,6-dihydro-2H-[1,3,5]thiadiazine, 5,6-dihydro-2H-[1,2,5]thiadiazine, 5,6-dihydro-4H-[1,2,5]thiadiazine, 5,6-dihydro-2H-[1,2,3]oxadiazine, 3,6-dihydro-2H-[1,2,5]oxadiazine, 5,6-dihydro-4H-[1,3,4]oxadiazine, 3,4-dihydro-2H-[1,2,5]oxadiazine, 5,6-dihydro-2H-[1,2,3]thiadiazine, 3,6-dihydro-2H-[1,2,5]thiadiazine, 5,6-dihydro-4H-[1,3,4]thiadiazine, 3,4-dihydro-2H-[1,2,5]thiadiazine, 5,6-dihydro-[1,4,3]oxathiazine, 5,6-dihydro-[1,4,2]oxathiazine, 2,3-dihydro-[1,4,3]oxathiazine, 2,3-dihydro-[1,4,2]oxathiazine, 4,5-dihydropyridine, 1,6-dihydropyridine, 5,6-dihydropyridine, 2H-pyran, 2H-thiin, 3,6-dihydropyridine, 2,3-dihydropyridazine, 2,5-dihydropyridazine, 4,5-dihydropyridazine, 1,2-dihydropyridazine, 2,3-dihydropyrimidine, 2,5-dihydropyrimidine, 5,6-dihydropyrimidine, 3,6-dihydropyrimidine, 4,5-dihydropyrazine, 5,6-dihydropyrazine, 3,6-dihydropyrazine, 4,5-dihydropyrazine, 1,4-dihydropyrazine, 1,4-dithiin, 1,4-dioxin, 2H-1,2-oxazine, 6H-1,2-oxazine, 4H-1,2-oxazine, 2H-1,3-oxazine, 4H-1,3-oxazine, 6H-1,3-oxazine, 2H-1,4-oxazine, 4H-1,4-oxazine, 2H-1,3-thiazine, 2H-1,4-thiazine, 4H-1,2-thiazine, 6H-1,3-thiazine, 4H-1,4-thiazine, 2H-1,2-thiazine, 6H-1,2-thiazine, 1,4-oxathiin, 2H,5H-1,2,3-triazine, 1H,4H-1,2,3-triazine, 4,5-dihydro-1,2,3-triazine, 1H,6H-1,2,3-triazine, 1,2-dihydro-1,2,3-triazine, 2,3-dihydro-1,2,4-triazine, 3H,6H-1,2,4-triazine, 1H,6H-1,2,4-triazine, 3,4-dihydro-1,2,4-triazine, 1H,4H-1,2,4-triazine, 5,6-dihydro-1,2,4-triazine, 4,5-dihydro-1,2,4-triazine, 2H,5H-1,2,4-triazine, 1,2-dihydro-1,2,4-triazine, 1H,4H-1,3,5-triazine, 1,2-dihydro-1,3,5-triazine, 1,4,2-dithiazine, 1,4,2-dioxazine, 2H-1,3,4-oxadiazine, 2H-1,3,5-oxadiazine, 6H-1,2,5-oxadiazine, 4H-1,3,4-oxadiazine, 4H-1,3,5-oxadiazine, 4H-1,2,5-oxadiazine, 2H-1,3,5-thiadiazine, 6H-1,2,5-thiadiazine, 4H-1,3,4-thiadiazine, 4H-1,3,5-thiadiazine, 4H-1,2,5-thiadiazine, 2H-1,3,4-thiadiazine, 6H-1,3,4-thiadiazine, 6H-1,3,4-oxadiazine and 1,4,2-oxathiazine, wherein the heterocycle is optionally vicinally fused with a saturated or unsaturated 5-, 6- or 7-membered ring containing 0, 1 or 2 atoms independently selected from N, O and S;

R^c is independently, in each instance, phenyl substituted by 0, 1 or 2 groups selected from halo, C_1-4alkyl, C_1-3haloalkyl, —OR^a and —NR^aR^a; or R^c is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the carbon atoms of the heterocycle are substituted by 0, 1 or 2 oxo groups, wherein the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents selected from halo, C_1-4alkyl, C_1-3haloalkyl, —OR^a and —NR^aR^a;

R^d is hydrogen or —CH₃;

R^e is, independently, in each instance, C_1-8alkyl substituted by 0, 1, 2, 3 or 4 substituents selected from halo, cyano, nitro, —C(═O)R^b, —C(═O)OR^b, —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)R^b, —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂R^b, —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)R^b, —S(═O)₂R^b, —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)R^b, —S(═O)₂N(R^a)C(═O)OR^b, —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)R^b, —N(R^a)C(═O)OR^b, —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂R^b, —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^a and —NR^aC_2-6alkylOR^a; and wherein the C_1-8alkyl is additionally substituted by 0 or 1 groups independently selected from R^g;

R^f is, independently, in each instance, R^e or H; and

R^g is, independently, in each instance, a saturated or unsaturated 5- or 6-membered monocyclic ring containing 1, 2 or 3 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the ring are substituted by 0 or 1 oxo groups.