- 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.
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.
Journal of medicinal chemistry (2016-12-17)
Peter Jones, R Ian Storer, Yogesh A Sabnis, Florian M Wakenhut, Gavin A Whitlock, Katherine S England, Takasuke Mukaiyama, Christoph M Dehnhardt, Jotham W Coe, Steve W Kortum, Jill E Chrencik, David G Brown, Rhys M Jones, John R Murphy, Thean Yeoh, Paul Morgan, Iain Kilty
PMID27983835
摘要
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.