Oxazolopyridin-7(4h)-one wrn inhibitors

A compound of Formula I″, or a pharmaceutically acceptable salt thereof:

• wherein Ring A represents:
• a) a 4-7 membered saturated or partially unsaturated bivalent monocyclic ring system selected from carbocyclylene and heterocyclylene (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur);
• or
• b) a 4-12 membered saturated or partially unsaturated bivalent bicyclic ring system that is fused, bridged, or spirocyclic selected from carbocyclylene and heterocyclylene (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur);
• wherein Ring A is substituted with 0-4 independently selected RA substituents;
• each of Y and Z is selected from N and O, wherein Y is N and Z is O or Y is O and Z is N, denotes a single or double bond, and the 5-membered ring comprising Z and Y is aromatic;
• L is a linker selected from —C(O)—, —S(O)—, —S(O)2—, and
• R1 is selected from one of groups a) to e):
• a) a 5-6 membered monocyclic heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur) optionally substituted with 1-3 groups independently selected from halogen, C1-C6alkyl, haloC1-C6alkyl, C3-C6cycloalkyl, C1-C6alkoxy, and C3-C6cycloalkoxy, wherein said 5-6 membered monocyclic heteroaryl is further substituted with 0-3 independently selected RA,
• b) a 9-10 membered bicyclic heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur) optionally substituted with 1 or 2 groups independently selected from C1-C6aliphatic, C3-C6cycloalkyl, C1-C6alkoxy, and C3-C6cycloalkoxy, wherein said 9-10 membered bicyclic heteroaryl is further substituted with 0-3 independently selected RA;
• c) a 4-7-membered saturated or partially unsaturated monocyclic heterocyclyl (having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), optionally substituted with 1 or 2 groups independently selected from C1-C6alkyl, C3-C6cycloalkyl, C1-C6alkoxy, and C3-C6cycloalkoxy, and —OR, wherein said 4-7 membered saturated or partially unsaturated monocyclic heterocyclyl is further substituted with 0-3 independently selected RA;
• d) a 4-12 membered saturated or partially unsaturated bicyclic ring system that is fused, bridged, or spirocyclic selected from carbocyclyl and heterocyclyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), wherein said carbocyclyl or heterocyclyl is substituted with 0-3 independently selected RA;
• and
• e) H, halogen, C1-C6aliphatic, C3-C7cycloalkyl, C1-C6alkylene-O—C1-C6alkyl, —CN, —OR, —NR10R11, —C(O)NR10R11, —CH2NR10R11, —SO2R12, wherein the C1-C6aliphatic, C3-C7cycloalkyl, or C1-C6alkylene-O—C1-C6alkyl is substituted with 0-5 independently selected RA;
• R10 is H, C1-C6aliphatic, haloC1-C6alkyl, C3-C6cycloalkyl, haloC3-C6cycloalkyl, —C(O)C3-C6cycloalkyl, —C(O) C1-C6alkyl, or a 5-6 membered heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur) optionally substituted with 1 or 2 groups independently selected from RA;
• R11 is H, C1-C6aliphatic, or C3-C6cycloalkyl, or R10 and R11 may combine to form a 5-6 membered ring optionally substituted with 1, 2, or 3 substituents independently selected from halogen, —OH, —CN, C1-C4alkoxy, and haloC1-C4alkoxy;
• R12 is C1-C6aliphatic, C3-C6cycloalkyl, or a 5-6 membered heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur) optionally substituted with 1 or 2 groups independently selected from halogen, C1-C6aliphatic, haloC1-C6alkyl, C1-C6alkoxy, C3-C6cycloalkyl, and C3-C6cycloalkoxy;
• RA is independently selected at each occurrence from the group consisting of optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), optionally substituted 4-7 membered saturated or partially unsaturated heterocyclyl (having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), halogen, optionally substituted C1-C6aliphatic, hydroxy-C1-C6alkyl, haloC1-C6alkyl, an optionally substituted C3-C6cycloalkyl, haloC3-C6cycloalkyl, C1-C6alkoxy, haloC1-C6alkoxy, C3-C6cycloalkoxy, haloC3-C6cycloalkoxy, C1-C6alkylene-O—C1-C6alkyl, —CN, —NO2, oxo, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —S(O)NR2, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)C(NR)NR2, —N(R)S(O)2NR2, and —N(R)S(O)2R;
• R2 is selected from C(RB)2C(O)N(R)R2A, C(RB)2C(RB)2C(O)N(R)R2A, C(RB)2C(RB)2N(R)C(O) N(R)R2A, and C(RB)2C(RB)2N(R)C(O)R2A,
• RB is independently selected at each occurrence from hydrogen, —CH3, and —CH2CH3, or two RB taken together with the carbon to which they are attached form a cyclopropyl ring;
• R2A is phenyl, pyridyl, cubanyl, a saturated or partially unsaturated 4-8 membered monocyclic ring, a saturated or partially unsaturated bridged, fused, or spirocyclic 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered ring, wherein said saturated or partially unsaturated monocyclic ring, or saturated or partially unsaturated bridged, fused, or spirocyclic ring contains 0, 1, 2, 3, or 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and wherein said phenyl, pyridyl, cubanyl, saturated or partially unsaturated monocyclic ring, or saturated or partially unsaturated bridged, fused, or spirocyclic ring are each optionally substituted with 1, 2, or 3 substituents independently selected from halogen, C1-C4aliphatic, haloC1-C4alkyl, C3-C6cycloalkyl, haloC3-C6cycloalkyl, —OH, —CN, C1-C4alkoxy, haloC1-C4alkoxy, C3-C6cycloalkoxy, haloC3-C6-cycloalkoxy and —SF5;
• or two substituents on adjacent atoms of the phenyl or pyridyl together with said adjacent atoms form a 4-7 membered carbocyclyl fused to the phenyl or pyridyl;
• or two substituents on adjacent atoms of the phenyl or pyridyl together with said adjacent atoms form a 4-7 membered heterocyclyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur) fused to the phenyl or pyridyl, wherein said 4-7 membered carbocyclyl or 4-7 membered heterocyclyl is substituted with 0-5 independently selected halogen, and wherein 2 substituents on the same atom of said saturated or partially unsaturated monocyclic ring, or saturated or partially unsaturated bridged, fused, or spirocyclic ring form a cyclic group selected from:
• an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclyl, and
• an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or
• R2A is 2-benzimidazolyl, 2-naphthyl, or 3-quinolinyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, C1-C4aliphatic, haloC1-C4alkyl, and —OH;
• R3 is hydrogen, C1-C4aliphatic, C3-C5cycloalkyl, C1-C4alkoxy, —NHR3A, —N(R3A)2, or C1-C4alkylthio, each of which, besides hydrogen, is optionally substituted with —OH, 1-5 independently selected halogen, —OR, —C(O)NR10R11, or N(R)C(O)R;
• each R3A is independently selected at each occurrence from C1-C4alkyl;
• R4 is phenyl or a first 5-6 membered heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur) wherein said phenyl or said first 5-6 membered heteroaryl are substituted with 0-5 RA or two substituents on adjacent atoms of said phenyl or said first 5-6 membered heteroaryl together with said adjacent atoms form a 4-7 membered carbocyclyl, a 4-7 membered heterocyclyl, or a second 5-6 membered heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur) that is fused to the phenyl or first 5-6 membered heteroaryl wherein said 4-7 membered carbocyclyl, 4-7 membered heterocyclyl, or second 5-6 membered heteroaryl are substituted with 0-3 RA;
• or
• R4 is a C1-C4alkyl, C1-C4alkoxy, or C3-C6cycloalkyl, each of which is substituted with 0-3 groups independently selected from halogen, —CN, —OH, oxo, NH2, C1-C4alkyl, C1-C4alkoxy, optionally substituted 5-6 membered heterocyclyl, and optionally substituted 5-6 membered heterocyclyloxy;
• each R is independently hydrogen, or an optionally substituted C1-6aliphatic group, an optionally substituted phenyl, an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclic ring, an optionally substituted 3-7 membered saturated or partially unsaturated heterocyclic ring (having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), or an optionally substituted 5-6 membered heteroaryl ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur);
• or
• two R groups on the same atom are taken together with the same atom to form an optionally substituted 4-7 membered saturated ring, 4-7 membered partially unsaturated ring, or 5-6 membered heteroaryl ring (wherein said 4-7 membered saturated ring and 4-7 membered partially unsaturated ring has 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur and wherein said 5-6 membered heteroaryl ring has 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur).