Synthesis and protein-tyrosine kinase inhibitory activities of flavonoid analogues

J Med Chem. 1991 Feb;34(2):798-806. doi: 10.1021/jm00106a047.


Treatment of o-hydroxyacetophenones 2a-e with excess lithium bis(trimethylsilyl)amide followed by dialkyl carbonates gave alkyl 3-(2-hydroxyaryl)-3-oxopropanoates 3a-e. The latter substances were transformed through the reaction of their magnesium chelates with benzoyl chlorides into a series of 3-(alkoxycarbonyl)-2-arylflavones, which were subsequently elaborated into a variety of flavonoids. These compounds were tested for their abilities to inhibit the in vitro protein-tyrosine kinase activity of p56lck, an enzyme which is thought to play a key role in mediating signal transduction from the CD4 receptor during lymphocyte activation. All of the active compounds had either an amino or a hydroxyl substituent at the 4'-position of the 2-aryl ring. The most active substance prepared in this study is compound 17c, which is approximately 1 order of magnitude more potent than the natural product quercetin (1). Compound 17c was a competitive inhibitor of p56lck with respect to ATP and was highly selective for the inhibition of protein-tyrosine over protein-serine/threonine kinases.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chemical Phenomena
  • Chemistry
  • Flavonoids / chemical synthesis*
  • Flavonoids / pharmacology
  • Genistein / analogs & derivatives
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Structure-Activity Relationship


  • Flavonoids
  • 4'-amino-6-hydroxyflavone
  • Genistein
  • Protein-Tyrosine Kinases