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 [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 616.07 Pathology
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2016
• Mô tả vật lý: Size: p. 767-786 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260684
• Chủ đề: 1. 60 applied life sciences; 2. Amides; 3. Assays; 4. Hydrocarbons; 5. Inhibition; 6. Peptides and proteins

Tóm tắt

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. Furthermore, 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.