Delta3- substituted quinoline or quinoxaline derivatives and their use as phosphatidylinositol 3-kinase ( PI3K) inhibitors

摘要

Substituted bicyclic heteroaryls having the structure: (I) R" X R XIR 3 ( 5 or any pharmaceutically-acceptable salt thereof, wherein: X1 is C(R 9) or N; X2 is C(R' 0) or N; Y is N(R" 1), 0 or S; which are useful to inhibit the biological activity of human PI3K6 and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints 10 with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiple sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The 15 present invention also enables methods for treating cancers that are mediated, dependent on or associated with pI 10S activity, including but not restricted to ;Ieukemias, such as Acute Myeloid leukaemia (AML) Myelo- dysplastic syndrome (MDS), myeloproliferative diseases (MPD), Chronic Myeloid Leukemia (CML), T-cell Acute Lymphoblastic Leukaemia ( T-ALL), B-cell Acute Lymphoblastic Leukaemia (B-ALL), 20 Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer.