Polymer-supported synthesis of pyridone-focused libraries as inhibitors of anaplastic lymphoma kinase

Tong Zhu, Zheng Yan, Alexander Chucholowski, Thomas R. Webb, Rongshi Li

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The optimization of screening hits on a promising new target for therapy of certain cancers involving anaplastic lymphoma kinase (ALK) inspired the development of this efficient solid-phase chemistry. A series of novel pyridones have been recently discovered as inhibitors of ALK, which led to the design of focused libraries around the pyridone scaffold. A stepwise process involving iterative template modification based on both medicinal chemistry insights and computational ranking of virtual libraries was employed in the design. The unique solid-phase chemistry has addressed the need for rapid optimization of this "early lead" series. Herein the methodology and scope of the chemistry, as well as its application for library synthesis, are discussed.

Original languageEnglish (US)
Pages (from-to)401-409
Number of pages9
JournalJournal of Combinatorial Chemistry
Volume8
Issue number3
DOIs
StatePublished - May 1 2006

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Pyridones
Chemistry
Inhibitor
Libraries
Polymers
Synthesis
Digital Libraries
Pharmaceutical Chemistry
Scaffolds
Series
Optimization
Scaffold
Screening
Iterative Process
Hits
Therapy
Template
Cancer
Ranking
Target

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Polymer-supported synthesis of pyridone-focused libraries as inhibitors of anaplastic lymphoma kinase. / Zhu, Tong; Yan, Zheng; Chucholowski, Alexander; Webb, Thomas R.; Li, Rongshi.

In: Journal of Combinatorial Chemistry, Vol. 8, No. 3, 01.05.2006, p. 401-409.

Research output: Contribution to journalArticle

Zhu, Tong ; Yan, Zheng ; Chucholowski, Alexander ; Webb, Thomas R. ; Li, Rongshi. / Polymer-supported synthesis of pyridone-focused libraries as inhibitors of anaplastic lymphoma kinase. In: Journal of Combinatorial Chemistry. 2006 ; Vol. 8, No. 3. pp. 401-409.
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