Imidazo[1,2-a]pyridinyl derivatives as irak4 inhibitors

A compound of formula (I′):

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from the group consisting of halogen, C1-5 alkyl, C3-6 cycloalkyl, —C1-2 alkyl-C3-6 cycloalkyl, C(O)NR4R5, C1-4 alkyl-NR4R5, a fully saturated 4 to 7 membered heterocycle containing 1 to 2 heteroatoms independently selected from nitrogen, sulfur and oxygen, 5 to 6 membered heteroaryl, phenyl, —C1-2 alkyl-C4-7 heterocycle, wherein the C4-7 heterocycle may be fully or partially saturated and contains 1 to 2 heteroatoms independently selected from nitrogen, sulfur and oxygen, —C1-2 alkyl-C5-6heteroaryl wherein the heteroaryl contains 1, 2 or 3 heteroatoms independently selected from nitrogen, sulfur and oxygen, —C1-4 alkyl-O—C1-2 alkyl, —C1-2 alkyl-O—C5-6 heteroaryl wherein the heteroaryl contains 1 or 2 heteroatoms independently selected from nitrogen, sulfur and oxygen, a fully saturated 5 to 10 membered bridged-carbocyclic ring, a 5 to 10 membered bridged-heterocyclic ring system having 1 to 2 heteroatoms independently selected from nitrogen and oxygen, a 5 to 10 membered fused heterobicyclic ring system having 1 to 2 heteroatoms independently selected from nitrogen and oxygen, and a 5 to 10 membered spiro heterobicyclic ring system having 1 to 2 heteroatoms independently selected from nitrogen and oxygen, wherein R1 may be optionally substituted with 1, 2 or 3 substituents which are independently selected from halo, nitrile, oxo, —C(O)OH, halo-substitutedC1-4 alkyl, hydroxy-substitutedC1-4 alkyl, C1-4 alkyl, C4-7heterocycle containing 1 to 2 heteroatoms independently selected from nitrogen and oxygen, C1-4 alkyl-O—C1-2 alkyl, hydroxy, C(O)R6 and C1-4 alkoxy;
• R2 is hydrogen, C1-4 alkyl or halogen;
• or
• R1 and R2 are taken together with their intervening atoms to form a 4 to 7 membered partially saturated carbocyclic ring or a partially saturated heterocyclic ring having one nitrogen said nitrogen may be optionally substituted with C1-4 alkyl;
• R4 and R5 are independently selected from hydrogen, hydroxy-substituted-C1-4 alkyl and C1-4 alkyl;
• or
• R4 and R5 are taken together with the nitrogen to which they are connected form a 4 to 7 membered saturated heterocyclic ring, said ring optionally having an additional heteroatom selected from nitrogen and oxygen wherein said nitrogen may be optionally substituted with C1-4 alkyl;
• R6 is C1-4 alkyl, halo-substituted-C1-4 alkyl or O—C1-4 alkyl;
• R3 is selected from the group consisting of
• ix. a 5 or 6 membered heteroaryl having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, said heteroaryl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of R7;
• x. Phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of R7;
• xi. a 6 membered partially saturated heterocycle having 1 to 2 nitrogen atoms, said heterocycle may be optionally substituted with 1 to 3 substituents independently selected from the group consisting of R7;
• and
• xii. an 8 to 10 membered fused bicyclic ring system optionally having 1, 2 or 3 heteroatoms independently selected from nitrogen and oxygen, said ring system is optionally substituted with 1 to 3 substituents independently selected from the group consisting of R7;
• X1 and X2 are independently selected from N, CH and CR8;
• provided at least one of X1 and X2 is CR8;
• R8 is selected from halogen, nitrile, NR4R5, —OR9 and a partially or fully saturated 4 to 7 membered heterocycle which contains 1 or 2 heteroatoms independently selected from nitrogen and oxygen, said C1-4alkyl and said heterocycle is optionally substituted with 1 to 3 substituents selected from R4a;
• R4a for each occurrence, is independently selected from hydrogen, oxo, C1-4 alkyl, halo-substitutedC1-4 alkyl, C1-4alkoxy, and C3-6cycloalkyl;
• or two R4a groups taken together with the carbon to which they are attached may combine to form a spiro 3-8 membered cycloalkyl;
• R9 is hydrogen, a C3-6cycloalkyl, a partially or fully saturated 4 to 7 membered heterocycle which contains 1 or 2 heteroatoms independently selected from nitrogen and oxygen, or a C1-5alkyl, wherein said C3-6cycloalkyl, said partially or fully saturated 4 to 7 membered heterocycle and said C1-5alkyl represented by R9 are optionally substituted with 1 to 3 substituents independently selected from halogen, hydroxyl, nitrile, oxo, NR4R5, halo-substitutedC1-4alkyl, C1-4alkoxy, halo-substituted C1-4alkoxy, C3-6cycloalkyl, phenyl and a 4 to 7 membered partially or fully saturated heterocycle containing 1 or 2 heteroatoms selected from nitrogen and oxygen, wherein said C3-6cycloalkyl, phenyl and 4 to 7 membered heterocycle may be optionally substituted with 1 to 3 R10;
• R10 is independently selected from oxo, halo, halo-substitutedC1-4 alkyl and C1-4 alkyl;
• R7 for each occurrence, is independently selected from C1-4 alkyl, nitrile, oxo, halo, halo-substitutedC1-4alkyl, —NR11R12, C1-4 alkoxy, halo-substitutedC1-4 alkoxy, a C3-6cycloalkyl, a C3-6cycloalkoxy, 4 to 7 membered partially or fully saturated heterocycle containing 1 or 2 heteroatoms selected from nitrogen and oxygen, and a 5 or 6 membered heteroaryl having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, said C3-6cycloalkyl and heteroaryl may be optionally substituted with 1 to 2 substituents independently selected from the group consisting of C1-4 alkyl, hydroxy and halogen and said C1-4 alkyl and C1-4alkoxy may be optionally substituted with C1-4alkoxy;
• and
• R11 and R12 are each independently selected from hydrogen, —C(O)C1-4 alkyl and C1-4 alkyl;
• or R11 and R12 may combine to form a 4 to 6 membered saturated ring optionally containing one additional heteroatom selected from nitrogen or oxygen wherein said additional nitrogen may be optionally substituted with C1-4 alkyl,
• provided when X1 is CR8, X2 is CH, and R8 is halogen, then R7 is not a 4 to 7 membered partially or fully saturated heterocycle containing 1 or 2 heteroatoms selected from nitrogen and oxygen;
• and provided that the compound is not: