Efforts towards the optimization of a bi-aryl class of potent IRAK4 inhibitors. Issue 17 (1st September 2016)

• Record Type: Journal Article
• Authors: Hanisak, Jennifer; Seganish, W. Michael; McElroy, William T.; Tang, Haiquin; Zhang, Rui; Tsui, Hon-Chung; Fischmann, Theirry; Tulshian, Deen; Tata, James; Sondey, Christopher; Devito, Kristine; Fossetta, James; Garlisi, Charles G.; Lundell, Daniel; Niu, Xiaoda
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 17(2016)
• Page Start: 4250
• Page End: 4255
• Publication Date: 2016-09-01
• Subjects: IRAK4 -- Interleukin receptor-associated kinases -- Toll-like receptors -- Inflammation -- SAR; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.07.048
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: IRAK4 has been identified as potential therapeutic target for inflammatory and autoimmune diseases. Herein we report the identification and initial SAR studies of a new class of pyrazole containing IRAK4 inhibitors designed to expand chemical diversity and improve off target activity of a previously identified series. These compounds maintain potent IRAK4 activity and desirable ligand efficiency. Rat clearance and a variety of off target activities were also examined, resulting in encouraging data with tractable SAR.