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

Rongshi Li, Liquan Xue, Tong Zhu, Qin Jiang, Xiaoli Cui, Zheng Yan, Danny McGee, Jian Wang, Vidyasagar Reddy Gantla, Jason C. Pickens, Doug McGrath, Alexander Chucholowski, Stephan W. Morris, Thomas R. Webb

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1006-1015
Number of pages10
JournalJournal of Medicinal Chemistry
Volume49
Issue number3
DOIs
StatePublished - Feb 9 2006
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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