Synthesis of 7-azaindoles and their pro-angiogenic and anti-inflammatory activities

Azaindole skeletons are prevalent in both natural products and pharmaceuticals, and they exhibit excellent biological activity. However, efficient synthetic strategies for accessing these compounds remain limited. Here, we synthesized a series of 7-azaindoles I-1-I-52 including 10 new compounds I-34 - I-43via double Csp²-H bond activations. The structures of these compounds were characterized using ¹H NMR, ¹³C NMR, and HR-MS. Their biological activities were evaluated in zebrafish models. The in vivo bioactivity data showed compounds I-47 and I-51 have significant pro-angiogenic effects, while compounds I-17, I-29, I-35 and I-37 exert potent anti-inflammatory effects. Moreover, the new compound I-37 alleviated inflammation in a concentration-dependent manner in both mechanical injury and lipopolysaccharide-induced inflammation models, which was associated with the inhibition of TNF-α and IL-6. This study not only provides a novel strategy for the synthesis of 7-azaindoles but also supports candidate compounds with pro-angiogenic and anti-inflammatory effects.