Substituted azaindoline derivatives as NIK inhibitors

A compound of Formula (I):

• a tautomer or a stereoisomeric form thereof, wherein
• R1 represents C1-4alkyl;
• R2 represents C1-6alkyl, or C1-6alkyl substituted with one R5;
• Y represents CR4 or N;
• R4 represents hydrogen or halo;
• R5 represents halo, cyano, Het3a, —NR6aR6b, or —OR7;
• R6a represents hydrogen or C1-4alkyl;
• R6b represents hydrogen;
• C1-4alkyl;
• C3-6cycloalkyl;
• —C(═O)—C1-4alkyl;
• —C(═O)—Het4;
• —S(═O)2—C1-4alkyl;
• —C(═O)—C1-4alkyl substituted with one substituent selected from the group consisting of —OH and —NR16aR16b;
• or C1-4alkyl substituted with one substituent selected from the group consisting of —OH and —S(═O)2—C1-4alkyl;
• R7 represents hydrogen, C1-4alkyl, —C1-4alkyl-NR8aR8b, —C(═O)—R9, —S(═O)2—OH, —P(═O)2—OH, —(C═O)—CH(NH2)—C1-4alkyl-Ar1, or —C1-4alkyl-Het3b;
• R8a represents hydrogen or C1-4alkyl;
• R8b represents hydrogen, C1-4alkyl, or C3-6cycloalkyl;
• R9 represents C1-4alkyl, or C1-6alkyl substituted with one substituent selected from the group consisting of —NH2, —COOH, and Het6;
• R16a and R16b each independently represents hydrogen, C1-4alkyl or C3-6cycloalkyl;
• R3 represents phenyl optionally substituted with one, two or three substituents each independently selected from the group consisting of halo;
• cyano;
• C1-6alkyl;
• —O—C1-4alkyl;
• —C(═O)—R10;
• —S(═O)2—C1-4alkyl;
• —S(═O)(═N—R20a)—C1-4alkyl;
• —O—C1-4alkyl substituted with one, two or three halo atoms;
• —O—C1-4alkyl-R12;
• C3-6cycloalkyl;
• —O—C3-6cycloalkyl;
• Het1a;
• —O-Het1b;
• R18;
• R21;
• —P(═O)—(C1-4alkyl)2;
• —NH—C(═O)—C1-4alkyl;
• —NH—C(═O)—Het1g;
• —NR17aR17b;
• C1-6alkyl substituted with one, two or three halo atoms;
• C1-4alkyl substituted with one, two or three —OH substituents;
• C1-4alkyl substituted with one R13;
• C1-4alkyl substituted with one R18;
• C2-6alkenyl;
• C2-6alkenyl substituted with one R13;
• C2-6alkynyl;
• and C2-6alkynyl substituted with one R13;
• R10 represents —OH, —O—C1-4alkyl, —NR11aR11b or Het2;
• R18 represents a 5-membered aromatic ring containing one, two or three N-atoms;
• wherein said 5-membered aromatic ring may optionally be substituted with one substituent selected from the group consisting of C1-4alkyl and C3-6cycloalkyl;
• R21 represents 3,6-dihydro-2H-pyran-4-yl or 1,2,3,6-tetrahydro-4-pyridinyl, wherein 1,2,3,6-tetrahydro-4-pyridinyl may optionally be substituted on the N-atom with C1-4alkyl or C3-6cycloalkyl;
• Het1a, Het1c and Het1d each independently represents a 4- to 7-membered monocyclic saturated heterocyclyl containing one or two heteroatoms each independently selected from O, S, S(═O)p and N;
• or a 6- to 11-membered bicyclic saturated heterocyclyl, including fused, spiro and bridged cycles, containing one, two or three heteroatoms each independently selected from O, S, S(═O)p and N;
• wherein said 4- to 7-membered monocyclic saturated heterocyclyl or said 6- to 11-membered bicyclic saturated heterocyclyl in Het1a, Het1c and Het1d may optionally be substituted, where possible, on one, two or three ring N-atoms with a substituent each independently selected from the group consisting of C1-4alkyl, C3-6cycloalkyl, and C1-4alkyl substituted with one substituent selected from the group consisting of —OH and —O—C1-4alkyl;
• and
• wherein said 4- to 7-membered monocyclic saturated heterocyclyl or said 6- to 11-membered bicyclic saturated heterocyclyl in Het1a, Het1c and Het1d may optionally be substituted on one, two or three ring C-atoms with one or two substituents each independently selected from the group consisting of —OH, halo, C1-4alkyl, cyano, —C(═O)—C1-4alkyl, —O—C1-4alkyl, NH2, —NH(C1-4alkyl), and —N(C1-4alkyl)2;
• Het1b, Het1e, Het1g, Het4, Het7 and Het8 each independently represents a 4- to 7-membered monocyclic saturated heterocyclyl, attached to the remainder of the molecule of Formula (I) through any available ring carbon atom, said Het1b, Het1e, Het1g, Het4, Het7 and Het8 containing one or two heteroatoms each independently selected from O, S, S(═O)p and N;
• wherein said 4- to 7-membered monocyclic saturated heterocyclyl in Het1b, Het1e, Het1g, Het4, Het7, and Het8 may optionally be substituted, where possible, on one or two ring N-atoms with a substituent each independently selected from the group consisting of C1-4alkyl, C3-6cycloalkyl, and C1-4alkyl substituted with one substituent selected from the group consisting of —OH and —O—C1-4alkyl;
• and
• wherein said 4- to 7-membered monocyclic saturated heterocyclyl in Het1b, Het1e, Het1g, Het4, Het7, and Het8 may optionally be substituted on one, two or three ring C-atoms with one or two substituents each independently selected from the group consisting of —OH, halo, C1-4alkyl, cyano, —C(═O)—C1-4alkyl, —O—C1-4alkyl, —NH2, —NH(C1-4alkyl), and —N(C1-4alkyl)2;
• Het2 represents a heterocyclyl of formula (b-1):
• (b-1) represents a N-linked 4- to 7-membered monocyclic saturated heterocyclyl optionally containing one additional heteroatom selected from O, S, S(═O)p and N, or a N-linked 6- to 11-membered bicyclic saturated heterocyclyl, including fused, spiro and bridged cycles, optionally containing one or two additional heteroatoms each independently selected from O, S, S(═O)p and N;
• wherein in case (b-1) contains one or two additional N-atoms, said one or two N-atoms may optionally be substituted with a substituent each independently selected from the group consisting of C1-4alkyl, C3-6cycloalkyl and Het7;
• and
• wherein (b-1) may optionally be substituted on one, two or three ring C-atoms with one or two substituents each independently selected from the group consisting of halo, —OH, cyano, C1-4alkyl, —O—C1-4alkyl, —NH2, —NH(C1-4alkyl), —N(C1-4alkyl)2, and C1-4alkyl-OH;
• R11b represents hydrogen;
• Het1e;
• C1-4alkyl;
• —C1-4alkyl-Het5;
• —C1-4alkyl-Het8;
• C1-4alkyl substituted with one, two or three substituents each independently selected from the group consisting of halo, —OH and —O—C1-4alkyl;
• C3-6cycloalkyl;
• or C3-6cycloalkyl substituted with one, two or three substituents each independently selected from the group consisting of halo, —OH and —O—C1-4alkyl;
• R13 represents —O—C1-4alkyl, —C(═O)NR15aR15b, —NR19aR19b, C3-6cycloalkyl, Het1d, or —C(═O)—Het1f;
• R12 represents —OH, —O—C1-4alkyl, —NR14aR14b, —C(═O)NR14cR14d, —S(═O)2—C1-4alkyl, —S(═O)(═N—R20b)—C1-4alkyl, C3-6cycloalkyl, Ar2, or Het1c;
• Ar1 represents phenyl optionally substituted with one hydroxy;
• Ar2 represents phenyl optionally substituted with one C1-4alkyl;
• Het3a, Het3b, Het5, Het6 and Het1f each independently represents a heterocyclyl of formula (c-1):
• (c-1) represents a N-linked 4- to 7-membered monocyclic saturated heterocyclyl optionally containing one additional heteroatom selected from O, S, S(═O)p and N;
• wherein in case (c-1) contains one additional N-atom, said additional N-atom may optionally be substituted with C1-4alkyl or C3-6cycloalkyl;
• and
• wherein (c-1) may optionally be substituted on one or two ring C-atoms atoms with one or two substituents each independently selected from the group consisting of halo, C1-4alkyl, and C3-6cycloalkyl;
• R11a, R14a, R14c, R15a, R17a and R19a each independently represents hydrogen or C1-4alkyl;
• R14b, R14d, R15b, R17b and R19b each independently represents hydrogen;
• C1-6alkyl;
• C3-6cycloalkyl;
• —C(═O)—C1-4alkyl;
• C1-4alkyl substituted with one substituent selected from the group consisting of halo, —OH and —O—C1-4alkyl;
• —C(═O)—C1-4alkyl substituted with one substituent selected from the group consisting of halo, —OH and —O—C1-4alkyl;
• or —S(═O)2—C1-4alkyl;
• R20a and R20b each independently represents hydrogen;
• C1-4alkyl;
• C3-6cycloalkyl;
• or C1-4alkyl substituted with one substituent selected from the group consisting of —OH and —O—C1-4alkyl;
• and
• p represents 1 or 2;
• or a pharmaceutically acceptable addition salt, or a solvate thereof.