Identification and synthesis of N-(thiophen-2-yl) benzamide derivatives as BRAF(V600E) inhibitors

Bioorg Med Chem Lett. 2013 Apr 15;23(8):2306-12. doi: 10.1016/j.bmcl.2013.02.072. Epub 2013 Feb 26.

Abstract

The V600E BRAF kinase mutation, which activates the downstream MAPK signaling pathway, commonly occurs in about 8% of all human malignancies and about 50% of all melanomas. In this study, we employed virtual screening and chemical synthesis to identify a series of N-(thiophen-2-yl) benzamide derivatives as potent BRAF(V600E) inhibitors. Structure-activity relationship studies of these derivatives revealed that compounds b40 and b47 are the two most potent BRAF(V600E) inhibitors in this series.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides / chemical synthesis
  • Benzamides / chemistry*
  • Benzamides / pharmacology*
  • Cell Proliferation / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Models, Molecular
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / chemistry
  • Structure-Activity Relationship

Substances

  • Benzamides
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf