Rapid synthesis of VX-745: p38 MAP kinase inhibition in Werner syndrome cells

Bioorg Med Chem Lett. 2007 Sep 15;17(18):5107-10. doi: 10.1016/j.bmcl.2007.07.016. Epub 2007 Jul 13.

Abstract

The p38 mitogen-activated protein kinase inhibitor VX-745 is prepared rapidly and efficiently in a four-step sequence using a combination of conductive heating and microwave-mediated steps. Its inhibitory activity was confirmed in hTERT immortalized HCA2 and WS dermal fibroblasts at 0.5-1.0 microM concentration by ELISA and immunoblot assay, and displays excellent kinase selectivity over the related stress-activated kinase JNK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Enzyme-Linked Immunosorbent Assay
  • Protein Kinase Inhibitors / pharmacology*
  • Pyridazines / chemical synthesis*
  • Pyridazines / pharmacology
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology
  • Werner Syndrome / enzymology*
  • Werner Syndrome / pathology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*

Substances

  • Protein Kinase Inhibitors
  • Pyridazines
  • Pyrimidines
  • p38 Mitogen-Activated Protein Kinases
  • VX-745