Document Report Card

ID: ALA1149386

Journal: J Med Chem

Title: Design and synthesis of 5-aryl-pyridone-carboxamides as inhibitors of anaplastic lymphoma kinase.

Authors: Li R, Xue L, Zhu T, Jiang Q, Cui X, Yan Z, McGee D, Wang J, Gantla VR, Pickens JC, McGrath D, Chucholowski A, Morris SW, Webb TR.

Abstract: Anaplastic lymphoma kinase (ALK) is a promising new target for therapy of certain cancers such as anaplastic large-cell lymphoma (ALCL) and inflammatory myofibroblastic tumor (IMT). We have identified a series of novel pyridones as kinase inhibitors of ALK by application of a stepwise process involving in vitro screening of a novel targeted library followed by iterative template modification based on medicinal chemistry insights and computational ranking of virtual libraries. Using this process, we discovered ALK-selective inhibitors with improved potency and selectivity. Herein the details of the design process and synthesis of these novel pyridones, along with their enzymatic and cell-based activity, are discussed.

CiteXplore: 16451066

DOI: 10.1021/jm050824x