Azalactam compounds as HPK1 inhibitors

A compound of Formula II

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from the group consisting of hydrogen, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, —N(R6)(R7), and (C3-C6)cycloalkyl, wherein said (C3-C6)cycloalkyl is optionally substituted with one to three substituents selected from the group consisting of halogen, hydroxy, (C1-C6)alkyl, and (C1-C6)alkoxy;
• R6 and R7 are each independently selected from the group consisting of hydrogen and (C1-C6)alkyl, wherein said (C1-C6)alkyl is optionally substituted with 1 to 3 substituents selected from the group consisting of halogen and hydroxy, or R6 and R7 taken together with the nitrogen to which they are attached form a (4- to 8-membered)heterocycloalkyl that is optionally substituted with one to three substituents selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, and halo(C1-C6)alkoxy;
• R2 is:
• i) a —(CH2)mN(R8)(R9), wherein m is an integer selected from 0, 1, 2, or 3, and R8 and R9 are each independently selected from the group consisting of hydrogen and (C1-C6)alkyl, wherein said (C1-C6)alkyl is optionally substituted with 1 to 3 substituents selected from the group consisting of halogen and hydroxy, or R8 and R9 taken together with the nitrogen to which they are attached form a (4- to 6-membered)heterocycloalkyl that is optionally substituted with one to three substituents selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, and halo(C1-C6)alkoxy;
• or
• ii) a (4- to 6-membered)heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one to three substituents selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, and halo(C1-C6)alkoxy;
• R5 is selected from the group consisting of hydrogen, halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, and halo(C1-C6)alkoxy;
• and
• R12 is selected from the group consisting of (C1-C6)alkyl, halo(C1-C6)alkyl, and —(CH2)n(C3-C6)cycloalkyl, wherein n is an integer 0 or 1.

A compound of Formula III

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from the group consisting of hydrogen, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, —N(R6)(R7), and (C3-C6)cycloalkyl, wherein said (C3-C6)cycloalkyl is optionally substituted with one to three substituents selected from the group consisting of halogen, hydroxy, (C1-C6)alkyl, and (C1-C6)alkoxy;
• R6 and R7 are each independently selected from the group consisting of hydrogen and (C1-C6)alkyl, wherein said (C1-C6)alkyl is optionally substituted with 1 to 3 substituents selected from the group consisting of halogen and hydroxy, or R6 and R7 taken together with the nitrogen to which they are attached form a (4- to 8-membered)heterocycloalkyl that is optionally substituted with one to three substituents selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, and halo(C1-C6)alkoxy;
• R2 is:
• i) a —(CH2)mN(R8)(R9), wherein m is an integer selected from 0, 1, 2, or 3, and R8 and R9 are each independently selected from the group consisting of hydrogen and (C1-C6)alkyl, wherein said (C1-C6)alkyl is optionally substituted with 1 to 3 substituents selected from the group consisting of halogen and hydroxy, or R8 and R9 taken together with the nitrogen to which they are attached form a (4- to 6-membered)heterocycloalkyl that is optionally substituted with one to three substituents selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, and halo(C1-C6)alkoxy;
• or
• ii) a (4- to 6-membered)heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one to three substituents selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, and halo(C1-C6)alkoxy;
• R5 is selected from the group consisting of hydrogen, halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, and halo(C1-C6)alkoxy;
• and
• R12 is selected from the group consisting of (C1-C6)alkyl, halo(C1-C6)alkyl, and —(CH2)n(C3-C6)cycloalkyl, wherein n is an integer 0 or 1.

A compound of Formula I

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from the group consisting of hydrogen, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, —N(R6)(R7), and (C3-C6)cycloalkyl, wherein said (C1-C6)alkyl, halo(C1-C6)alkyl, and (C3-C6)cycloalkyl are optionally substituted with one to three substituents selected from the group consisting of halogen, hydroxy, cyano, (C1-C6)alkyl, and (C1-C6)alkoxy;
• R6 and R7 are each independently selected from the group consisting of hydrogen and (C1-C6)alkyl, wherein said (C1-C6)alkyl is optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, (C1-C6)alkoxy, cyano, and hydroxy, or R6 and R7 taken together with the nitrogen to which they are attached form a (4- to 8-membered)heterocycloalkyl that is optionally substituted with one to three substituents selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, and halo(C1-C6)alkoxy, wherein said (C1-C6)alkyl, and halo(C1-C6)alkyl are optionally substituted with one to three substituents selected from the group consisting of halogen, hydroxy, cyano, (C1-C6)alkyl, and (C1-C6)alkoxy;
• R1a is H;
• R2 is CH2N(R8)(R9), wherein R8 and R9 are each independently selected from the group consisting of hydrogen and (C1-C6)alkyl, wherein said (C1-C6)alkyl is optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, (C1-C6)alkoxy, cyano, and hydroxy, or R8 and R9 taken together with the nitrogen to which they are attached form a (4- to 6-membered)heterocycloalkyl that is optionally substituted with one to three substituents selected from the group consisting of halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, and halo(C1-C6)alkoxy, wherein said (C1-C6)alkyl and halo(C1-C6)alkyl are optionally substituted with one to three substituents selected from the group consisting of halogen, hydroxy, cyano, and (C1-C6)alkoxy;
• and
• R3 is H;
• X is carbon;
• R5 is hydrogen;
• a is 1;
• and
• R4 is a (4- to 6-membered)heterocycloalkyl or a (5- to 10-membered)heteroaryl, wherein said (4- to 6-membered)heterocycloalkyl and (5- to 10-membered)heteroaryl are optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, cyano, oxo, hydroxy, —N(R10)(R11), (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, and —(CH2)n(C3-C6)cycloalkyl, wherein said (C1-C6)alkyl and halo(C1-C6)alkyl are optionally substituted with one to three substituents selected from the group consisting of halogen, hydroxy, cyano, and (C1-C6)alkoxy, and wherein n is an integer selected from 0, 1, or 2;
• and wherein R10 and R11 are each independently selected from the group consisting of hydrogen and (C1-C6)alkyl, wherein said (C1-C6)alkyl is optionally substituted with 1 to 3 substituents selected from the group consisting of halogen and hydroxy.

A compound or pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of

• 4-[(methylamino)methyl]-6-[methyl(propan-2-yl)amino]-2-[6-(4-propyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl]-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one;
• 4-[(methylamino)methyl]-6-[(2R)-2-methylpyrrolidin-1-yl]-2-[6-(4-propyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl]-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one;
• 4-[(methylamino)methyl]-2-[6-(5-methyl-4-propyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl]-6-[(2R)-2-methylpyrrolidin-1-yl]-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one;
• 4-[(methylamino)methyl]-6-[methyl(propan-2-yl)amino]-2-[6-(5-methyl-4-propyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl]-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one;
• and
• 4-(aminomethyl)-2-[6-(4-ethyl-5-methyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl]-6-[(2S)-2-methylpyrrolidin-1-yl]-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one.