Structure-activity relationship study of EphB3 receptor tyrosine kinase inhibitors.


Journal Article

A structure-activity relationship study for a 2-chloroanilide derivative of pyrazolo[1,5-a]pyridine revealed that increased EphB3 kinase inhibitory activity could be accomplished by retaining the 2-chloroanilide and introducing a phenyl or small electron donating substituents to the 5-position of the pyrazolo[1,5-a]pyridine. In addition, replacement of the pyrazolo[1,5-a]pyridine with imidazo[1,2-a]pyridine was well tolerated and resulted in enhanced mouse liver microsome stability. The structure-activity relationship for EphB3 inhibition of both heterocyclic series was similar. Kinase inhibitory activity was also demonstrated for representative analogs in cell culture. An analog (32, LDN-211904) was also profiled for inhibitory activity against a panel of 288 kinases and found to be quite selective for tyrosine kinases. Overall, these studies provide useful molecular probes for examining the in vitro, cellular and potentially in vivo kinase-dependent function of EphB3 receptor.

Full Text

Cited Authors

  • Qiao, L; Choi, S; Case, A; Gainer, TG; Seyb, K; Glicksman, MA; Lo, DC; Stein, RL; Cuny, GD

Published Date

  • November 2009

Published In

Volume / Issue

  • 19 / 21

Start / End Page

  • 6122 - 6126

PubMed ID

  • 19783434

Pubmed Central ID

  • 19783434

Electronic International Standard Serial Number (EISSN)

  • 1464-3405

International Standard Serial Number (ISSN)

  • 0960-894X

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2009.09.010


  • eng