Pteridinone compounds and uses thereof

A method for inducing ER stress in a patient in need thereof, comprising administering to said patient a compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• Ring A is selected from a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, indanyl, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 8-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-8 membered saturated or partially unsaturated bridged bicyclic carbocyclic ring, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• L is a covalent bond or a C1-6 bivalent straight or branched saturated or unsaturated hydrocarbon chain wherein one to three methylene units of the chain are independently and optionally replaced with -Cy-, —O—, —C(R)2—, —CH(R)—, —CH(OR)—, —CR(OR)—, —C(D)2-, —C(F)2—, —N(R)—, —N(R)C(O)—, —C(O)N(R)—, —N(R)C(O)O—, —OC(O)N(R)—, —N(R)C(O)N(R)—, —N(R)S(O)2—, —S(O)2N(R)—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —S(O)—, —S(O)2—, or —Si(R)2—, wherein -Cy- is an optionally substituted bivalent group selected from phenylenyl, cyclopropylenyl, cyclobutylenyl, cyclopentylenyl, cyclohexylenyl, furylenyl, tetrahydrofurylenyl, azetidylenyl, pyrrolidylenyl, piperidylenyl, triazolylenyl, pyrrolylenyl, pyrazolylenyl, pyridylenyl, 2,4,5,6-tetrahydrocyclopenta[c]pyrazolylenyl, or thiazolylenyl;
• R1 is hydrogen;
• each of R2 and R2′ is independently hydrogen, RD, or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or
• R2 and R2′ are optionally taken together to form ═CH2 or ═CH—(C1-3 aliphatic);
• R3 is hydrogen, RD, or an optionally substituted C1-6 aliphatic group;
• R4 is RD, —CD2OH, or an optionally substituted C1-3 aliphatic group;
• R5 is hydrogen, —C(O)R, —C(O)OR, —C(O)NR2, an optionally substituted 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a C1-3 aliphatic group;
• each of R6 is independently halogen, —CN, —NO2, —C(O)R, —C(O)OR, —C(O)NR2, —NR2, —NRC(O)R, —NRC(O)OR, —NRS(O)2R, —OR, —P(O)R2, —SR, —SF5, —S(CF3)5, —S(O)R, —S(O)2R, —S(O)(NH)R, —C(═NR)—OR, —O—C(═NR)—R, or R;
• or
• two R6 groups are optionally taken together to form ═O;
• each R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen and sulfur, optionally substituted with 1-2 oxo groups;
• RD is a C1-4 aliphatic group wherein one or more hydrogens are replaced by deuterium;
• X is N or CH;
• and
• n is 0, 1, 2, 3, 4 or 5,
• wherein said patient has a cancer selected from the group consisting of astrocytoma, bile duct cancer, bladder cancer, brain cancer, breast cancer, cervical cancer, colorectal cancer, esophagus cancer, germ cell cancer, glioblastoma, glioma, head and neck cancer, kidney cancer, leukemia, liver cancer, lung cancer, lymphoma, mesothelioma, multiple myeloma, neuroblastoma, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma, skin cancer, thyroid cancer, and uterine cancer.