Isoquinoline derivatives as perk inhibitors

A compound according to Formula (II):

• wherein:
• R11 is selected from:
• bicycloheteroaryl,
• substituted bicycloheteroaryl,
• heteroaryl, and
• substituted heteroaryl,
• where said substituted bicycloheteroaryl and said substituted heteroaryl are substituted with from one to five substituents independently selected from:
• fluoro,
• chloro,
• bromo,
• iodo,
• C1-6alkyl,
• C1-6alkyl substituted with from 1 to 5 substituents independently selected from:
• fluoro, chloro, bromo, iodo, C1-4alkyloxy, —OH, C1-4alkyl, cycloalkyl, —COOH, —CF3, —NO2, —NH2 and —CN,
• —OH,
• hydroxyC1-6alkyl,
• —COOH,
• tetrazole,
• cycloalkyl,
• oxo,
• —OC1-6alkyl,
• —CF3,
• —CF2H,
• —CFH2,
• —CONH2,
• —CON(H)C1-3alkyl,
• diC1-4alkylaminoC1-4alkyl,
• aminoC1-6alkyl,
• —CN,
• heterocycloalkyl,
• heterocycloalkyl substituted with from 1 to 4 substituents independently selected from:
• C1-4alkyl, C1-4alkyloxy, —OH, —COOH, —CF3, —C1-4alkylOC1-4alkyl, oxo, —NO2, —NH2 and —CN,
• —NO2,
• —NH2,
• —N(H)C1-3alkyl, and
• N(C1-3alkyl)2;
• R12 is selected from:
• aryl,
• aryl substituted with from one to five substituents independently selected from:
• fluoro, chloro, bromo, iodo, C1-4alkyl, cycloalkyl, C1-4alkyloxy, —OH, —COOH, —CF3, —C1-4alkylOC1-4alkyl, —NO2, —NH2, —OC(H)F2, —C(H)F2, —OCH2F, —CH2F, —CHF2, —OCF3, and —CN,
• heteroaryl,
• heteroaryl substituted with from one to five substituents independently selected from:
• fluoro, chloro, bromo, iodo, C1-4alkyl, cycloalkyl, C1-4alkyloxy, —OH, —COOH, —CF3, —C1-4alkylOC1-4alkyl, —NO2, —NH2, —OC(H)F2, —C(H)F2, —OCH2F, —CH2F, —OCF3, and —CN,
• bicycloheteroaryl,
• bicycloheteroaryl substituted with from one to five substituents independently selected from:
• fluoro, chloro, bromo, iodo, C1-4alkyl, C1-4alkyloxy, —OH, —COOH, —CF3, —C1-4alkylOC1-4alkyl, —NO2, —NH2, cycloalkyl, —OC(H)F2, —C(H)F2, —OCH2F, —CH2F, —CHF2, —OCF3, —CN, and cycloalkyl;
• R13, R14, R15, and R16 are each independently selected from hydrogen, fluoro, chloro, bromo, iodo, —CF3, and —CH3;
• and
• R17 is selected from:
• hydrogen, C1-6alkyl, cycloalkyl, aminoC1-6alkyl, —CF3, —CH3, fluoro, chloro, bromo and iodo;
• and
• X is O, S, C(═O), CR250R350,
• R250 and R350 are independently selected from hydrogen, —CH3,
• —CF3, —OH, —NH2,
• or R250 and R350 taken together with the carbon atoms to which they are attached represent a 3 or 4 member cycloalkyl;
• or a pharmaceutically acceptable salt thereof.

The method according to claim 13 wherein said cancer is selected from:

• breast cancer, inflammatory breast cancer, ductal carcinoma, lobular carcinoma, colon cancer, pancreatic cancer, insulinomas, adenocarcinoma, ductal adenocarcinoma, adenosquamous carcinoma, acinar cell carcinoma, glucagonoma, skin cancer, melanoma, metastatic melanoma, lung cancer, small cell lung cancer, non-small cell lung cancer, squamous cell carcinoma, adenocarcinoma, large cell carcinoma, brain (gliomas), glioblastomas, astrocytomas, glioblastoma multiforme, Bannayan-Zonana syndrome, Cowden disease, Lhermitte-Duclos disease, Wilm's tumor, Ewing's sarcoma, Rhabdomyosarcoma, ependymoma, medulloblastoma, head and neck, kidney, liver, melanoma, ovarian, pancreatic, adenocarcinoma, ductal adenocarcinoma, adenosquamous carcinoma, acinar cell carcinoma, glucagonoma, insulinoma, prostate, sarcoma, osteosarcoma, giant cell tumor of bone, thyroid,
• lymphoblastic T cell leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, hairy-cell leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia, chronic neutrophilic leukemia, acute lymphoblastic T cell leukemia, plasmacytoma, Immunoblastic large cell leukemia, mantle cell leukemia, multiple myeloma, megakaryoblastic leukemia, multiple myeloma, acute megakaryocytic leukemia, promyelocytic leukemia, erythroleukemia,
• malignant lymphoma, hodgkins lymphoma, non-hodgkins lymphoma, lymphoblastic T cell lymphoma, Burkitt's lymphoma, follicular lymphoma,
• neuroblastoma, bladder cancer, urothelial cancer, vulval cancer, cervical cancer, endometrial cancer, renal cancer, mesothelioma, esophageal cancer, salivary gland cancer, hepatocellular cancer, gastric cancer, nasopharangeal cancer, buccal cancer, cancer of the mouth, GIST (gastrointestinal stromal tumor), neuroendocrine cancers and testicular cancer.