The discovery of novel N-(2-pyrimidinylamino) benzamide derivatives as potent hedgehog signaling pathway inhibitors

Bioorg Med Chem Lett. 2013 Dec 15;23(24):6777-83. doi: 10.1016/j.bmcl.2013.10.022. Epub 2013 Oct 17.

Abstract

Hedgehog signaling pathway inhibitors are emerging as new therapeutic intervention against cancer. A novel series of N-(2-pyrimidinylamino) benzamide derivatives as hedgehog signaling pathway inhibitors were designed and synthesized. Most compounds presented significant inhibitory effect on hedgehog signaling pathway, among which 21 compounds exhibited more potent than vismodegib. Furthermore, compound 6a showed moderate pharmacokinetic properties in vivo, representing a promising lead compound for further exploration.

Keywords: Hedgehog signaling; Hedgehog signaling pathway inhibitors; Lead compound; Synthesize.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / chemical synthesis
  • Benzamides / chemistry*
  • Benzamides / pharmacokinetics
  • Benzamides / pharmacology*
  • Drug Design
  • Drug Evaluation, Preclinical
  • Half-Life
  • Hedgehog Proteins / antagonists & inhibitors
  • Hedgehog Proteins / metabolism*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Structure-Activity Relationship

Substances

  • Benzamides
  • Hedgehog Proteins
  • Pyrimidines
  • benzamide
  • pyrimidine