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NLM AIDSLINE
Synthesis and potent anti-HIV-1 activity of novel 6-benzyluracil analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine.
Danel K; Larsen E; Pedersen EB; Vestergaard BF; Nielsen C; Department of
October 30, 1996
J Med Chem. 1996 Jun 7;39(12):2427-31. Unique Identifier : AIDSLINE

Ethyl 2-alkyl-4-aryl-3-oxobutyrates were synthesized from the corresponding arylacetonitriles and 2-bromo esters. Condensation of the butyrates with thiourea followed by treatment with chloroacetic acid afforded the 5-alkyl-6-(arylmethyl)uracils. Condensation of the uracils with acetals using trimethylsilyl triflate (TMS triflate) as a catalyst gave acyclic 5-alkyl-6-(arylmethyl)uracil derivatives. 6-Benzyl-5-ethyluracil was also condensed with methyl 5-O-(tert-butyldiphenylsilyl)-2-deoxy-3-O-(phenoxythiocarbonyl+ ++)-alpha,beta-D-erythro-pentofuranoside, followed by Barton reduction and deprotection, to give the anomers of 6-benzyl-5-ethyl-2',3'-dideoxyuridine. Alkylation of the uracils with alkyl chloromethyl sulfides gave new thio analogues of HEPT. All new N1-substituted uracils were tested for activity against HIV-1, and the thio analogues were found extremely potent.

Alkylation Antiviral Agents/*CHEMICAL SYNTHESIS/PHARMACOLOGY/TOXICITY Cell Division/DRUG EFFECTS Comparative Study Drug Design Human HIV-1/*DRUG EFFECTS/PHYSIOLOGY Molecular Structure Nuclear Magnetic Resonance Structure-Activity Relationship T-Lymphocytes/DRUG EFFECTS/VIROLOGY Thymine/*ANALOGS & DERIVATIVES/PHARMACOLOGY Uracil/*ANALOGS & DERIVATIVES/CHEMICAL SYNTHESIS/PHARMACOLOGY/ TOXICITY Virus Replication/*DRUG EFFECTS JOURNAL ARTICLE

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