2-Benzimidazolyl-9-(chroman-4-yl)-purinone derivatives as JAK3 inhibitors

A novel class of Janus tyrosine kinase 3 (JAK3) inhibitors based on a 2-benzimidazoylpurinone core structure is described. Through substitution of the benzimidazoyl moiety and optimization of the N-9 substituent of the purinone, compound 24 was identified incorporating a chroman-based functional group. Compound 24 shows excellent kinase activity, good oral bioavailability and demonstrates efficacy in an acute mechanistic mouse model through inhibition of interleukin-2 (IL-2) induced interferon-γ (INF-γ) production.

Graphical abstractA novel class of 2-benzimidazoylpurinone-based JAK3 inhibitors with excellent kinase activity is described. Compound 24 demonstrates good oral bioavailability and in vivo efficacy in an acute mechanistic mouse model.Figure optionsDownload full-size imageDownload as PowerPoint slide