Deuterated dhodh inhibitors

A compound according to Formula (I):

• or an enantiomer, diastereomer, tautomer, prodrug, solvate, or pharmaceutically acceptable salt thereof, wherein
• A is selected from a 5-membered heteroaryl, cyclopentenyl and heterocyclopentenyl, having one or more hydrogen atoms optionally replaced by deuterium,
• said A is unsubstituted or substituted with 1 to 5 substituents independently selected from the group consisting of halogen, CN, NO2, oxo, OH, C1-4-alkyl, O—C1-4-alkyl, fluoro-C1-4-alkyl and O-fluoro-C1-4-alkyl, CO2H and SO3H, having one or more hydrogen atoms in alkyl optionally replaced by deuterium;
• B is selected from the group consisting of 5- to 10-membered cycloalkyl, 4- to 10-membered heterocycloalkyl containing 1 to 4 heteroatoms independently selected from N, O and S, 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1 to 6 heteroatoms independently selected from N, O and S,
• wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of halogen, —CN, —NO2, oxo, C1-4-alkyl, C0-6-alkylene-OR27, C0-6-alkylene-(3- to 6-membered cycloalkyl), C0-6-alkylene-(3- to 6-membered heterocycloalkyl), C0-6-alkylene-S(═O)n(═NR29)mR27, C0-6-alkylene-NR27S(═O)x(═NR29)yR27, C0-6-alkylene-S(═O)x(═NR29)yNR27R28, C0-6-alkylene-NR27 S(═O)x(═NR29)yNR27R28, C0-6-alkylene-CO2R27, C0-6-alkylene-O—COR27, C0-6-alkylene-CONR27R28, C0-6-alkylene-NR27—COR27, C0-6-alkylene-NR27—CONR27R28, C-0-6-alkylene-O—CONR27R28, C0-6-alkylene-NR27—CO2R27, C0-6-alkylene-NR27R28,
• wherein alkyl, alkylene, 3- to 6-membered cycloalkyl and 3- to 6-membered heterocycloalkyl is unsubstituted or substituted with 1 to 6 substituents independently selected from halogen, —CN, oxo, —OH, C1-4-alkyl, halo-C1-4-alkyl, —O—C1-4-alkyl and —O-halo-C1-4-alkyl;
• and wherein optionally two adjacent substituents in the aryl or heteroaryl moiety form a 5- to 8-membered partially unsaturated cycle optionally containing 1 to 3 heteroatoms independently selected from O, S or N, wherein this additional cycle is optionally substituted with 1 to 4 substituents independently selected from halogen, —CN, oxo, —OH, C1-4-alkyl, halo-C1-4-alkyl, —O—C1-4-alkyl and —O-halo-C1-4-alkyl,
• and wherein the residue —NR2 on ring B is in a 1,4-orientation with respect to ring C, ring B or its substituents having one or more hydrogen atoms optionally replaced by deuterium;
• C is selected from the group consisting of 5- to 10-membered cycloalkyl, 4- to 10-membered heterocycloalkyl containing 1 to 4 heteroatoms independently selected from N, O and S, 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1 to 6 heteroatoms independently selected from N, O and S,
• wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of halogen, —CN, —NO2, oxo, C1-4-alkyl, C0-6-alkylene-OR31, C0-6-alkylene-(3- to 6-membered cycloalkyl), C0-6-alkylene-(3- to 6-membered heterocycloalkyl), C0-6-alkylene-S(═O)n(═NR33)mR31, C0-6-alkylene-NR31S(═O)x(═NR33)yR31, C0-6-alkylene-S(═O)x(═NR33)yNR31R32, C0-6-alkylene-NR31 S(═O)x(═NR33)yNR31R32, C0-6-alkylene-CO2R31, C0-6-alkylene-O—COR31, C0-6-alkylene-CONR31R32, C0-6-alkylene-NR31—COR31, C0-6-alkylene-NR31—CONR31R32, C0-6-alkylene-O—CONR31R32, C0-6-alkylene-NR31—CO2R31, C0-6-alkylene-NR31R32,
• wherein alkyl, alkylene, 3- to 6-membered cycloalkyl and 3- to 6-membered heterocycloalkyl is unsubstituted or substituted with 1 to 6 substituents independently selected from halogen, —CN, oxo, —OH, C1-4-alkyl, halo-C1-4-alkyl, —O—C1-4-alkyl and —O-halo-C1-4-alkyl;
• and wherein optionally two adjacent substituents in the aryl or heteroaryl moiety form a 5- to 8-membered partially unsaturated cycle optionally containing 1 to 3 heteroatoms independently selected from O, S or N,
• wherein this additional cycle is optionally substituted with 1 to 4 substituents independently selected from halogen, —CN, oxo, —OH, C1-4-alkyl, halo-C1-4-alkyl, —O—C1-4-alkyl and —O-halo-C1-4-alkyl,
• ring C or its substituents having one or more hydrogen atoms optionally replaced by deuterium;
• X is selected from H, D, halogen, —CN, —NO2, C1-6-alkyl, —O—C1-6-alkyl, O-halo-C1-6-alkyl, C0-6-alkylene-OR41, C0-6-alkylene-(3- to 6-membered cycloalkyl), C0-6-alkylene-(3- to 6-membered heterocycloalkyl), C0-6-alkylene-S(═O)n(═NR43)mR41, C0-6-alkylene-NR41S(═O)x(═NR43)yR41, C0-6-alkylene-S(═O)x(═NR43)yNR41R42, C0-6-alkylene-NR41S(═O)x(═NR43)yNR41R42, C0-6-alkylene-CO2R41, C0-6-alkylene-O—COR41, C0-6-alkylene-CONR41R42, C0-6-alkylene-NR41—COR41, C0-6-alkylene-NR41—CONR41R42, C0-6-alkylene-O—CONR41R42, C0-6-alkylene-NR41—CO2R41, C0-6-alkylene-NR41R42, wherein heterocycloalkyl comprises 1, 2, 3 or 4 heteroatoms independently selected from N, O, or S,
• wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl is unsubstituted or substituted with 1 to 6 substituents independently selected from halogen, —CN, oxo, —OH, C1-4-alkyl, halo-C1-4-alkyl, —O—C1-4-alkyl and —O-halo-C1-4-alkyl,
• X or its substituents having one or more hydrogen atoms optionally replaced by deuterium;
• R1 is selected from H and D;
• R2 is selected from H and C1-6-alkyl,
• wherein alkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, —CN, C1-4-alkyl, halo-C1-4-alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), —OH, oxo, —O—C1-4-alkyl and —O-halo-C1-4-alkyl, wherein heterocycloalkyl comprises 1, 2, 3 or 4 heteroatoms independently selected from N, O, or S,
• R2 or its substituents having one or more hydrogen atoms optionally replaced by deuterium;
• R27, R28, R31, R32, R41, R42 are independently selected from H, C1-6-alkyl, 3- to 6-membered cycloalkyl or 3- to 6-membered heterocycloalkyl,
• wherein alkyl, cycloalkyl or heterocycloalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, —CN, C1-4-alkyl, halo-C1-4-alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), —OH, oxo, —O—C1-4-alkyl and —O-halo-C1-4-alkyl, wherein heterocycloalkyl comprises 1, 2, 3 or 4 heteroatoms independently selected from N, O, or S,
• R27 and/or R28 and/or R31 and/or R32 and/or R41 and/or R42 or its substituents, respectively, having one or more hydrogen atoms optionally replaced by deuterium;
• or R27 and R28, R31 and R32, R41 and R42, respectively, when taken together with the nitrogen to which they are attached complete a 3- to 6-membered cycle containing carbon atoms and optionally containing 1 or 2 heteroatoms selected from O, S or N;
• and
• wherein this cycle is unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, —CN, C1-4-alkyl, halo-C1-4-alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), —OH, oxo, —O—C1-4-alkyl and —O-halo-C1-4-alkyl,
• R27 and/or R28 and/or R31 and/or R32 and/or R41 and/or R42 or its substituents, respectively, having one or more hydrogen atoms optionally replaced by deuterium;
• R29, R33, R43 are independently selected from H, —CN, —NO2, C1-6-alkyl, —CO—O—C1-6-alkyl, 3- to 6-membered cycloalkyl or 3- to 6-membered heterocycloalkyl,
• wherein alkyl, cycloalkyl or heterocycloalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, —CN, C1-4-alkyl, halo-C1-4-alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), —OH, oxo, —O—C1-4-alkyl and —O-halo-C1-4-alkyl, wherein heterocycloalkyl comprises 1, 2, 3 or 4 heteroatoms independently selected from N, O, or S,
• R29 and/or R33 and/or R43 or its substituents, respectively, having one or more hydrogen atoms optionally replaced by deuterium;
• n, m, x, y are independently selected from 0 to 2;
• with the proviso that the sum of integer m and n for the residue linked to the same sulfur atom is independently selected from 0 to 2;
• with the proviso that the sum of integer x and y for the residue linked to the same sulfur atom is independently selected from 1 or 2;
• provided that at least one hydrogen in A, B, C, R2, R27, R28, R29, R31, R32, R33, R41, R42, R43 and/or X is replaced by deuterium;
• provided, that the level of deuterium incorporation at each substituent designated as deuterium is at least 52.5%.