Synthesis of N²-modified 7-methylguanosine 5'-monophosphates as nematode translation inhibitors

Bioorg Med Chem. 2012 Aug 1;20(15):4781-9. doi: 10.1016/j.bmc.2012.05.078. Epub 2012 Jun 10.

Abstract

Preparative scale synthesis of 14 new N(2)-modified mononucleotide 5' mRNA cap analogues was achieved. The key step involved use of an S(N)Ar reaction with protected 2-fluoro inosine and various primary and secondary amines. The derivatives were tested in a parasitic nematode, Ascaris suum, cell-free system as translation inhibitors. The most effective compound with IC(50) ∼0.9μM was a N(2)-p-metoxybenzyl-7-methylguanosine-5'-monophosphate 35.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascaris suum / embryology
  • Ascaris suum / enzymology
  • Ascaris suum / metabolism*
  • Dose-Response Relationship, Drug
  • Luciferases, Renilla / antagonists & inhibitors*
  • Luciferases, Renilla / metabolism
  • Molecular Structure
  • Protein Synthesis Inhibitors / chemical synthesis
  • Protein Synthesis Inhibitors / chemistry
  • Protein Synthesis Inhibitors / pharmacology*
  • RNA Cap Analogs / chemical synthesis
  • RNA Cap Analogs / chemistry
  • RNA Cap Analogs / pharmacology*
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / metabolism
  • Structure-Activity Relationship

Substances

  • Protein Synthesis Inhibitors
  • RNA Cap Analogs
  • RNA, Messenger
  • 7-methylguanosine-5'-monophosphate
  • Luciferases, Renilla