2. Academic Validation
  3. Synthesis and activity of new aryl- and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain

Synthesis and activity of new aryl- and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain

  • J Med Chem. 2003 Sep 11;46(19):3953-6. doi: 10.1021/jm0205705.
J Scott Sawyer 1,  Bryan D Anderson,  Douglas W Beight,  Robert M Campbell,  Michael L Jones,  David K Herron,  John W Lampe,  Jefferson R McCowan,  William T McMillen,  Nicholas Mort,  Stephen Parsons,  Edward C R Smith,  Michal Vieth,  Leonard C Weir,  Lei Yan,  Faming Zhang,  Jonathan M Yingling
Affiliations

Affiliation

  • 1 Discovery Chemistry Research and Technology, The Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. jss@lilly.com
PMID: 12954047 DOI: 10.1021/jm0205705
Abstract

Pyrazole-based inhibitors of the transforming growth factor-beta type I receptor kinase domain (TbetaR-I) are described. Examination of the SAR in both enzyme- and cell-based in vitro assays resulted in the emergence of two subseries featuring differing selectivity versus p38 MAP kinase. A common binding mode at the active site has been established by successful cocrystallization and X-ray analysis of potent inhibitors with the TbetaR-I receptor kinase domain.

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