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Updated: Jun 19, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
2-Benzimidazolyl-9-(chroman-4-yl)-purinone derivatives as JAK3 inhibitors
Andrew G Cole1, Adolph C Bohnstedt, Vidyadhar Paradkar
1Ligand Pharmaceuticals, Inc, Cranbury, NJ 08512, USA. acole@ligand.com
Abstract:
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-gamma (INF-gamma) production.
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