Bromodomain inhibitors and uses thereof

A method of treating a cancer selected from adenocarcinoma, adenoid cystic carcinoma, adult T-cell leukemia/lymphoma, bladder cancer, blastoma, bone cancer, breast cancer, brain cancer, carcinoma, myeloid sarcoma, cervical cancer, colorectal cancer, diffuse large B-cell lymphoma, esophageal cancer, follicular lymphoma, gastrointestinal cancer, glioblastoma multiforme, glioma, gallbladder cancer, gastric cancer, head and neck cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, intestinal cancer, kidney cancer, laryngeal cancer, leukemia, lung cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, mesothelioma, midline carcinoma, multiple myeloma, neuroblastoma, ocular cancer, optic nerve tumor, oral cancer, ovarian cancer, pituitary tumor, primary central nervous system lymphoma, prostate cancer, pancreatic cancer, pharyngeal cancer, renal cell carcinoma, rectal cancer, sarcoma, skin cancer, soft tissue sarcoma, spinal tumor, small intestine cancer, stomach cancer, T-cell lymphoma, testicular cancer, thyroid cancer, throat cancer, urogenital cancer, urothelial carcinoma, uterine cancer, vaginal cancer, and Wilms' tumor in a patient in need thereof, comprising administering to the patient a compound of formula II-A:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is H, alkyl, aralkyl, aryl, heteroaryl, halo, ORA, NRARB, S(O)qRA, C(O)RA, C(O)ORA, OC(O)RA, or C(O)NRARB;
• each RA is independently optionally substituted alkyl, containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• optionally substituted aryl;
• optionally substituted heteroaryl;
• optionally substituted heterocyclic;
• optionally substituted carbocyclic;
• or hydrogen;
• each RB is independently optionally substituted alkyl, containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• optionally substituted aryl;
• optionally substituted heteroaryl;
• optionally substituted heterocyclic;
• optionally substituted carbocyclic;
• or hydrogen;
• Ring A is benzo;
• RC is a 3-7 membered saturated, partially unsaturated or completely unsaturated carbocyclic ring;
• a 3-7 membered aryl ring;
• or a 3-7 membered saturated, partially unsaturated, or completely unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein RC is optionally substituted with 1-5 independently selected R4;
• R2 and R3 are each independently H, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, —OR, —SR, —CN, —N(R′)(R″), —C(O)R, —C(S)R, —CO2R, C(O)N(R′)(R″), —C(O)SR, or —(CH2)pRx;
• or
• R2 and R3 together with the atoms to which each is attached, forms an optionally substituted 3-7 membered saturated or partially unsaturated spiro-fused ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each Rx is independently halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, —OR, —SR, —CN, —N(R′)(R″), —C(O)R, —C(S)R, —CO2R, —C(O)N(R′)(R″), —C(O)SR, —C(O)C(O)R, —C(O)CH2C(O)R, —C(S)N(R′)(R″), —C(S)OR, —S(O)R, —SO2R, —SO2N(R′)(R″), —N(R′)C(O)R, —N(R′)C(O)N(R′)(R″), —N(R′)C(S)N(R′)(R″), —N(R′)SO2R, —N(R′)SO2N(R′)(R″), —N(R′)N(R′)(R″), —N(R′)C(═N(R′))N(R′)(R″), —C═NN(R′)(R″), —C═NOR, —C(═N(R′))N(R′)(R″), —OC(O)R, —OC(O)N(R′)(R″);
• each R is independently hydrogen, C1-6 aliphatic, a 5-6 membered aryl ring, a 3-7 membered saturated, partially unsaturated, or completely unsaturated carbocyclic ring, a 7-12 membered bicyclic saturated, partially unsaturated, or completely unsaturated carbocyclic ring, a 3-7 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 3-7 membered saturated, partially unsaturated, or completely unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 7-12 membered bicyclic saturated, partially unsaturated, or completely unsaturated heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 7-12 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each of which is optionally substituted;
• each R′ is independently —R, —C(O)R, —C(S)R, —CO2R, —C(O)N(R)2, —C(S)N(R)2, —S(O)R, —SO2R, —SO2N(R)2, or two R on the same nitrogen are taken together with their intervening atoms to form a 3-7 membered monocyclic saturated, partially unsaturated, or completely unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 7-12 membered bicyclic saturated, partially unsaturated, or completely unsaturated fused heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 3-7 membered monocyclic heteroaryl ring;
• or a 7-12 membered bicyclic heteroaryl;
• each of which is optionally substituted;
• each R″ is independently —R, —C(O)R, —C(S)R, —CO2R, —C(O)N(R)2, —C(S)N(R)2, —S(O)R, —SO2R, —SO2N(R)2, or two R on the same nitrogen are taken together with their intervening atoms to form a 3-7 membered monocyclic saturated, partially unsaturated, or completely unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 7-12 membered bicyclic saturated, partially unsaturated, or completely unsaturated fused heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 3-7 membered monocyclic heteroaryl ring;
• or a 7-12 membered bicyclic heteroaryl;
• each of which is optionally substituted;
• or
• R′ and R″, together with the atoms to which each is attached, can form a 3-7 membered monocyclic saturated, partially unsaturated, or completely unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 7-12 membered bicyclic saturated, partially unsaturated, or completely unsaturated fused heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 3-7 membered monocyclic heteroaryl ring;
• or a 7-12 membered bicyclic heteroaryl;
• each of which is optionally substituted;
• each R4 is independently optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl, halogen, —OR, —SR, —N(R′)(R″), —CN, —NO2, —C(O)R, —C(S)R, —CO2R, —C(O)N(R′)(R″), —C(O)SR, —C(O)C(O)R, —C(O)CH2C(O)R, —C(S)N(R′)(R″), —C(S)OR, —S(O)R, —SO2R, —SO2N(R′)(R″), —N(R′)C(O)R, —N(R′)C(O)N(R′)(R″), —N(R′)C(S)N(R′)(R″), —N(R′)SO2R, —N(R′)SO2N(R′)(R″), —N(R′)N(R′)(R″), —N(R′)C(═N(R′))N(R′)(R″), —C═NN(R′)(R″), —C═NOR, —C(═N(R′))N(R′)(R″), —OC(O)R, or —OC(O)N(R1)(R″);
• each R5 is independently —R, halogen, —OR, —SR, —N(R′)(R″), —CN, or —NO2;
• n is 0-5;
• q is 0, 1, or 2;
• and
• p is 1-6.

A method of treating a cancer selected from acute myeloid leukemia/MDS, adenocarcinoma, adenoid cystic carcinoma, adult T-cell leukemia/lymphoma, bladder cancer, blastoma, bone cancer, breast cancer, Burkitt's lymphoma, brain cancer, carcinoma, myeloid sarcoma, cervical cancer, colorectal cancer, diffuse large B-cell lymphoma, esophageal cancer, follicular lymphoma, gastrointestinal cancer, glioblastoma multiforme, glioma, gallbladder cancer, gastric cancer, head and neck cancer, intestinal cancer, kidney cancer, laryngeal cancer, leukemia, leukemia, lung cancer, lymphoma, liver cancer, small cell lung cancer, non-small cell lung cancer, mesothelioma, midline carcinoma, multiple myeloma, neuroblastoma, ocular cancer, optic nerve tumor, oral cancer, ovarian cancer, pituitary tumor, prostate cancer, pancreatic cancer, pharyngeal cancer, renal cell carcinoma, rectal cancer, sarcoma, skin cancer, soft tissue sarcoma, spinal tumor, small intestine cancer, stomach cancer, testicular cancer, thyroid cancer, throat cancer, urogenital cancer, urothelial carcinoma, uterine cancer, vaginal cancer, and Wilms' tumor, in a patient in need thereof, comprising administering to the patient a compound represented by the following structural formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• R5a is selected from hydrogen, halo, and alkoxy;
• R5b is selected from hydrogen, halo, and alkyl;
• RC is selected from phenyl, heteroaryl, and saturated heterocyclyl, wherein the group represented by RC is optionally substituted with 1 to 2 substituents independently selected from halo, —CN, alkyl, alkoxy, haloalkoxy, haloalkyl, and carbamyl;
• and
• R′ is selected from hydrogen, alkyl, and alkoxyalkyl.