Antiviral and cytostatic evaluation of the novel 6-acyclic chain substituted thymine derivatives

Antivir Chem Chemother. 2005;16(5):327-38. doi: 10.1177/095632020501600505.

Abstract

A series of the novel 5-methyl pyrimidine derivatives with an acyclic side chain at the C-6 position were synthesized using lithiation of a 2,4-dimethoxy-5,6-dimethyl pyrimidine and subsequent nucleophilic addition or substitution reactions of the organolithium intermediate thus obtained with acetaldehyde, epichlorhydrine, fluorinated ketones and fluorinated ester. The novel compounds were evaluated for their cytostatic and antiviral activities. Among all the compounds evaluated, two fluorinated acyclic pyrimidine derivatives showed the highest cytostatic activities. The compound containing a 2-hydroxy-3,3,3-trifluoro-1-propenyl side chain exhibited a pronounced effect against breast carcinoma (MCF-7, IC50=8.38 micorg/ml), while the compound with a 2-fluoromethyl-2-acetoxypropyl chain exhibited moderate effect against cervical carcinoma (HeLa, IC50=19.73 microg/ml).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Microbial Sensitivity Tests
  • Thymine / chemistry*
  • Thymine / pharmacology*

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Thymine