Grignard-mediated synthesis and preliminary biological evaluation of novel 3-substituted farnesyl diphosphate analogues

Bioorg Med Chem Lett. 2000 Aug 7;10(15):1763-6. doi: 10.1016/s0960-894x(00)00337-1.


A series of substituents was installed at the 3 position of farnesyl diphosphate through a copper-cyanide mediated coupling of a vinyl triflate with various Grignard reagents. These novel FPP mimetics were then evaluated as inhibitors of or substrates for mammalian protein farnesyl transferase. The IC50 values for these compounds range from 18 to 10,100 nm, with the 3-isopropenyl analogue being one of the most potent FPP-mimetic mFTase inhibitors yet synthesized.

Publication types

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

MeSH terms

  • Drug Evaluation
  • Molecular Mimicry
  • Polyisoprenyl Phosphates / chemical synthesis*
  • Polyisoprenyl Phosphates / chemistry
  • Polyisoprenyl Phosphates / pharmacology*
  • Sesquiterpenes


  • Polyisoprenyl Phosphates
  • Sesquiterpenes
  • farnesyl pyrophosphate