New protein farnesyltransferase inhibitors in the 3-arylthiophene 2-carboxylic acid series: diversification of the aryl moiety by solid-phase synthesis

J Enzyme Inhib Med Chem. 2013 Feb;28(1):163-71. doi: 10.3109/14756366.2011.643302. Epub 2012 Jan 11.

Abstract

A new synthetic pathway was devised to reach tetrasubstituted 3-arylthiophene 2-carboxylic acids in a three-step solid-phase synthesis. This very efficient methodology provided more than 20 new compounds that were evaluated for their ability to inhibit protein farnesyltransferase from different species as well as Trypanosoma brucei and Plasmodium falciparum proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Carboxylic Acids / chemistry*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Farnesyltranstransferase / antagonists & inhibitors*
  • Farnesyltranstransferase / genetics
  • Humans
  • Molecular Sequence Data
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / growth & development
  • Solid-Phase Synthesis Techniques / methods*
  • Structure-Activity Relationship
  • Thiophenes / chemistry
  • Trypanosoma brucei brucei / drug effects
  • Trypanosoma brucei brucei / enzymology
  • Trypanosoma brucei brucei / growth & development

Substances

  • Carboxylic Acids
  • Enzyme Inhibitors
  • Thiophenes
  • Farnesyltranstransferase