1-Benzyl derivatives of 5-(arylamino)uracils as anti-HIV-1 and anti-EBV agents

Mikhail S. Novikov, Robert W. Buckheit, Kartik Temburnikar, Anastasia L. Khandazhinskaya, Alexander V. Ivanov, Katherine L. Seley-Radtke

Research output: Contribution to journalArticlepeer-review

Abstract

Pyrimidine analogs have long found use over a broad chemotherapeutic spectrum. In an effort to further explore the antiviral potential of several uracil derivatives previously synthesized in our laboratories, a series of benzylated pyrimidines were designed and synthesized. Introduction of the benzyl residue onto the 5-phenylaminouracil scaffold was carried out using 2,4-bis(trimethylsilyloxy)pyrimidine with the corresponding benzyl bromides. Similarly, 1-benzyl-5-(benzylamino)- and 1-benzyl-5-(phenethylamino)uracils were obtained via amination of 1-benzyl-5-bromouracils with benzylamine or phenylethylamine. The results of the broad screen antiviral studies revealed that compounds 5 and 11 exhibit promising inhibitory activity against HIV-1 in CEM-SS culture. A 50% protective effect was observed at concentrations of 11.9 and 9.5 μ, respectively. Moreover, compounds 8 and 3 exhibited good inhibitory effects against EBV in K cell culture with EC50 values of 2.3 and 12 μM, respectively. The synthesis and biological studies are detailed herein.

Original languageEnglish (US)
Pages (from-to)8310-8314
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number23
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

Keywords

  • Antiviral
  • EBV
  • HIV
  • Pyrimidine
  • Uracil

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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