Synthesis and evaluation of 4-(2-pyrimidinylamino) benzamides inhibitors of hedgehog signaling pathway

Bioorg Med Chem Lett. 2014 Feb 1;24(3):983-8. doi: 10.1016/j.bmcl.2013.12.050. Epub 2013 Dec 17.

Abstract

A novel series of hedgehog signaling pathway inhibitors has been designed based on the 4-(2-pyrimidinylamino) benzamides scaffold. The synthesis and SAR of these compounds are described. Optimization leads to the identification of compound 3c, a potent and orally available agent with improved physicochemical and pharmacokinetic properties.

Keywords: Hedgehog signaling pathway; Inhibitors; Pharmacokinetic properties; SAR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides / chemical synthesis*
  • Benzamides / chemistry
  • Benzamides / pharmacology*
  • Hedgehog Proteins / antagonists & inhibitors*
  • Humans
  • Inhibitory Concentration 50
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Signal Transduction / drug effects*
  • Structure-Activity Relationship

Substances

  • Benzamides
  • Hedgehog Proteins
  • Pyrimidines