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 language | English (US) |
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Pages (from-to) | 8310-8314 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 18 |
Issue number | 23 |
DOIs | |
State | Published - Dec 1 2010 |
Externally published | Yes |
Keywords
- Antiviral
- EBV
- HIV
- Pyrimidine
- Uracil
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry