Antiproliferation 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, or a pharmaceutical composition thereof,
• wherein:
• Ring A is ring selected from phenyl, a 5-7 membered saturated or partially unsaturated carbocyclic ring, a 8-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered 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;
• each R1 is independently hydrogen, or C1-3 aliphatic optionally substituted by 1-6 halogen;
• or
• two R1 groups are optionally taken together with their intervening atoms to form a 5-8 membered partially unsaturated fused carbocyclic ring;
• each of R2 is independently hydrogen, halogen, —CN, —NO2, —C(O)OR, —C(O)NR2, —NR2, —NRC(O)R, —NRC(O)OR, —NRS(O)2R, —OR, —P(O)R2, —SR, —S(O)R, —S(O)2R, —S(O)(NH)R, —S(O)2NR2, or R;
• or
• two R2 groups are optionally taken together to form ═O;
• or
• two R2 groups are optionally taken together with their intervening atoms to form a 3-8 membered saturated spirocyclic ring having 0-2 heteroatoms independently selected from nitrogen, oxygen or sulfur;
• each R3 is independently hydrogen, —OH, or C1-3 aliphatic;
• or
• two R3 groups are optionally taken together to form ═O;
• or
• two R3 groups are optionally taken together to form ═CH2;
• or
• two R3 groups are optionally taken together with their intervening atoms to form a 3-8 membered saturated spirocyclic ring having 0-2 heteroatoms independently selected from nitrogen, oxygen or sulfur;
• or
• two R3 groups are optionally taken together with their intervening atoms to form a 5-8 membered saturated bridged bicyclic ring having 0-2 heteroatoms independently selected from nitrogen, oxygen or sulfur;
• 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 7-10 membered saturated spirobicyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered saturated or partially unsaturated fused bicyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 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:
• 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;
• is a single bond or a double bond;
• X is —O—;
• m is 0, 1, or 2;
• n is 0, 1, 2, 3, 4 or 5;
• and
• p is 0, 1, or 2,
• 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.