Azaindole derivatives as potential kinase inhibitors and their SARs elucidation.

Currently, heterocycles have occupied an important position in the fields of drug design. Among them, azaindole moiety is regarded as one privileged scaffold to develop therapeutic agents. Since two nitrogen atoms of azaindole increase the possibility to form hydrogen bonds in the adenosine triphosphate (ATP)-binding site, azaindole derivatives are important sources of kinase inhibitors. Moreover, some of them have been on the market or in clinical trials for the treatment of some kinase-related diseases (e.g., vemurafenib, pexidartinib, decernotinib). In this review, we focused on the recent development of azaindole derivatives as potential kinase inhibitors based on kinase targets, such as adaptor-associated kinase 1 (AAK1), anaplastic lymphoma kinase (ALK), AXL, cell division cycle 7 (Cdc7), cyclin-dependent kinases (CDKs), dual-specificity tyrosine (Y)-phosphorylation regulated kinase 1A (DYRK1A), fibroblast growth factor receptor 4 (FGFR4), phosphatidylinositol 3-kinase (PI3K) and proviral insertion site in moloney murine leukemia virus (PIM) kinases. Meanwhile, the structure-activity relationships (SARs) of most azaindole derivatives were also elucidated. In addition, the binding modes of some azaindoles complexed with kinases were also investigated during the SARs elucidation. This review may offer an insight for medicinal chemists to rationally design more potent kinase inhibitors bearing the azaindole scaffold.