1439809-93-4Relevant academic research and scientific papers
Structure-based discovery of C-2 substituted imidazo-pyrrolopyridine JAK1 inhibitors with improved selectivity over JAK2
Labadie, Sharada,Dragovich, Peter S.,Barrett, Kathy,Blair, Wade S.,Bergeron, Philippe,Chang, Christine,Deshmukh, Gauri,Eigenbrot, Charles,Ghilardi, Nico,Gibbons, Paul,Hurley, Christopher A.,Johnson, Adam,Kenny, Jane R.,Kohli, Pawan Bir,Kulagowski, Janusz J.,Liimatta, Marya,Lupardus, Patrick J.,Mendonca, Rohan,Murray, Jeremy M.,Pulk, Rebecca,Shia, Steven,Steffek, Micah,Ubhayakar, Savita,Ultsch, Mark,Van Abbema, Anne,Ward, Stuart,Zak, Mark
, p. 7627 - 7633 (2013/02/21)
Herein we describe our successful efforts in obtaining C-2 substituted imidazo-pyrrolopyridines with improved JAK1 selectivity relative to JAK2 by targeting an amino acid residue that differs between the two isoforms (JAK1: E966; JAK2: D939). Efforts to improve cellular potency by reducing the polarity of the inhibitors are also detailed. The X-ray crystal structure of a representative inhibitor in complex with the JAK1 enzyme is also disclosed.
