(pyridin-2-yl)amine derivatives as tgf-beta r1 (alk5) inhibitors for the treatment of cancer

A compound of Formula (I):

• wherein:
• Ring A is a 5 or 6 membered heteroaromatic ring optionally containing an additional nitrogen atom as a ring member and is optionally fused to a phenyl or pyridinyl ring, and Ring A is optionally substituted by one or two groups independently selected from halo, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, phenyl, pyridinyl, a 4-6 membered cyclic ether, and C3-C6 cycloalkyl;
• R1 is selected from H, halo, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C3-C6 cycloalkyl, 5-6 membered heterocyclyl containing N, O or S as a ring member, phenyl, and 5-6 membered heteroaryl containing one or two nitrogen atoms as ring members,
• wherein said C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C3-C6 cycloalkyl, phenyl, 5-6 membered heterocyclyl, and 5-6 membered heteroaryl are each optionally substituted with one or two groups selected from R2;
• wherein R2 is independently selected at each occurrence from halo, CN, —OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, and C3-C6 cycloalkyl;
• Cy is a ring selected from C3-C6 cycloalkyl, phenyl, and 5-6 membered heteroaryl containing one or two nitrogen atoms as ring members, and is optionally further substituted with one or two groups selected from halo, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;
• and
• L is a divalent linker selected from a bond, CR2, —(CR2)2-4—, —O—(CR2)1-3—, and —(CR2)m—X—(CR2)n—, wherein
• R is independently selected at each occurrence from H, F, and C1-C4 alkyl;
• or two R groups on the same carbon can be taken together with the carbon to which they are attached to form a 3-6 membered cycloalkyl ring or 3-6 membered cyclic ether;
• m is 0, 1, or 2;
• n is 0, 1 or 2;
• and
• X is a 5-membered heteroaromatic ring containing one to four heteroatoms selected from N, O and S as ring members;
• or a pharmaceutically acceptable salt thereof.

A compound of Formula (II):

• wherein:
• Ring A is a 5 or 6 membered heteroaromatic ring optionally containing an additional nitrogen atom as a ring member and optionally fused to a phenyl or pyridinyl ring, and Ring A is optionally substituted by one or two groups independently selected from halo, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, phenyl, pyridinyl, a 4-6 membered cyclic ether, and C3-C6 cycloalkyl;
• R1 is selected from CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C3-C6 cycloalkyl, 5-6 membered heterocyclyl containing N, O or S as a ring member, phenyl, and 5-6 membered heteroaryl containing one or two nitrogen atoms as ring members,
• wherein said C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C3-C6 cycloalkyl, 5-6 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted with one or two groups selected from Q1;
• wherein Q1 is independently selected at each occurrence from halo, CN, —OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, and C3-C6 cycloalkyl;
• L1 is a divalent linker selected from —C(R9)2—, —(C(R10)2)2-4—, —O—(C(R10)2)1-3—, and —(C(R10)2)m—X—C(R10)2)n—;
• wherein
• each R9 is independently C1-C2 alkyl or halo, or two R9 can be taken together with the carbon atom to which both are attached to form a 3-6 membered cycloalkyl ring or 3-6 membered cyclic ether;
• R10 is independently selected at each occurrence from H, F, and C1-C4 alkyl;
• or two R10 groups on the same carbon can be taken together with the carbon to which they are attached to form a 3-6 membered cycloalkyl ring or 3-6 membered cyclic ether;
• m is 0, 1, or 2;
• n is 0, 1 or 2;
• X is a pyrazolyl, triazolyl, or tetrazolyl ring;
• Z2 is selected from CH, CQ2, and N;
• and
• q is 0 or 1;
• and
• Q2 is selected from halo, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;
• or a pharmaceutically acceptable salt thereof.