Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin
- Jones, Peter
- Storer, Ian
- Sabnis, Yogesh A.
- Wakenhut, Florian M.
- Whitlock, Gavin A.
- England, Katherine S.
- Mukaiyama, Takasuke
- Dehnhardt, Christoph M.
- Coe, Jotham W.
- Kortum, Steve W.
- Chrencik, Jill E.
- Brown, David G.
- Jones, Rhys M.
- Murphy, John R.
- Yeoh, Thean
- Morgan, Paul
- Kilty, Iain
Publication date
December 2016
DOI Publisher
American Chemical Society (ACS)Abstract
By use of a structure-based computational method for identification of structurally novel Janus kinase (JAK) inhibitors predicted to bind beyond the ATP binding site, a potent series of indazoles was identified as selective pan-JAK inhibitors with a type 1.5 binding mode. Optimization of the series for potency and increased duration of action commensurate with inhaled or topical delivery resulted in potent pan-JAK inhibitor 2 (PF-06263276), which was advanced into clinical studies
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