Synthesis and significant cytostatic activity of 7-hetaryl-7-deazaadenosines

J Med Chem. 2011 Aug 11;54(15):5498-507. doi: 10.1021/jm2005173. Epub 2011 Jul 11.


A series of 7-aryl- and 7-hetaryl-7-deazaadenosines was prepared by the cross-coupling reactions of unprotected or protected 7-iodo-7-deazaadenosines with (het)arylboronic acids, stannanes, or zinc halides. Nucleosides bearing 5-membered heterocycles at the position 7 exerted potent in vitro antiproliferative effects against a broad panel of hematological and solid tumor cell lines. Cell cycle analysis indicated profound inhibition of RNA synthesis and induction of apoptosis in treated cells. Intracellular conversion to triphosphates has been detected with active compounds. The triphosphate metabolites showed only a weak inhibitory effect on human RNA polymerase II, suggesting potentially other mechanisms for the inhibition of RNA synthesis and quick onset of apoptosis. Initial in vivo evaluation demonstrated an effect of 7-(2-thienyl)-7-deazaadenine ribonucleoside on the survival rate in syngeneic P388D1 mouse leukemia model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Kinase / antagonists & inhibitors
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cytostatic Agents / chemical synthesis*
  • Cytostatic Agents / pharmacology*
  • Humans
  • Mice
  • RNA Polymerase II / antagonists & inhibitors
  • Tubercidin / analogs & derivatives*
  • Tubercidin / chemical synthesis
  • Tubercidin / pharmacology


  • Antineoplastic Agents
  • Cytostatic Agents
  • Adenosine Kinase
  • RNA Polymerase II
  • Tubercidin