PI3K (phosphatidylinositol 3-kinase) is a member of the unique and conserved family of intracellular lipid kinases, which is capable of phosphorylating the 3′-OH group on phosphatidylinositols. According to different structures and substrates for phosphorylation, PI3Ks can be divided into three classes: I, II and III, wherein Class I PI3K is a hot spot in the present study. Class I PI3K plays an important role in the regulation of immune cells which have PI3K activity and are helpful for pro-tumourigenic effect of inflammatory cells (Coussens and Werb, Nature, 2002, 420, 860-867), so that it has therapeutic values for the treatment of various forms of cancerous diseases, including solid tumors (such as carcinomas and sarcomas), leukemias and lymphoid malignancies. Class I PI3K consists of p110 unit and p85 unit. At present, there are four known p110 subunits, namely p110α, p110β, p110γ and p110δ, where p110δ mainly occurs in spleen and hematopoietic cells including leukocytes such as T cells, dendritic cells, neutrophils, mast cells, B cells and macrophages. PI3Kδ is fully involved in mammalian immune system functions such as T cell function, dendritic cell function, neutrophil activity, mast cell activation, B cell activation. Thus, PI3Kδ is also involved in a variety of diseases associated with abnormal immune response, such as allergic reactions, inflammatory diseases, inflammation-mediated angiogenesis, rheumatoid arthritis, autoimmune diseases such as lupus erythematosus, asthma, emphysema and other respiratory diseases.
Drug research targeting PI3K pathway has been carried out for many years and has certain clinical success. Particularly, the recent discovery found that selective PI3Kδ inhibitors have a significant effect in the treatment of cancer and other diseases. However, there residue a need to develop superior PI3K inhibitors, particularly selective PI3Kδ inhibitors, to specifically regulate and/or mediate the transduction of PI3K and related protein kinases in order to be used in the treatment of diseases associated with PI3K kinase-mediated events.