The discovery of tricyclic pyridone JAK2 inhibitors. Part 1: Hit to lead

This paper describes the discovery and design of a novel class of JAK2 inhibitors. Furthermore, we detail the optimization of a screening hit using ligand binding efficiency and log D. These efforts led to the identification of compound 41, which demonstrates in vivo activity in our study. (C) 2010 Elsevier Ltd. All rights reserved.