Synthesis of N-1-Alkylated 6-Benzyluracil-5-carboxylic Esters as Potential Non-Nucleoside Reverse Transcriptase Inhibitors

Janus S. Larsen; Erik B. Pedersen; Claus Nielsen

doi:10.1055/s-2004-829137

PAPER

Synthesis of N-1-Alkylated 6-Benzyluracil-5-carboxylic Esters as Potential Non-Nucleoside Reverse Transcriptase Inhibitors

Janus S. Larsen^a, Erik B. Pedersen*^a, Claus Nielsen^b
^a Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
Fax: +4566158780; e-Mail: ebp@chem.sdu.dk ;
^b Retrovirus Laboratory, Department of Virology, State Serum Institute, Artillerivej 5, 2300 Copenhagen, Denmark

Abstract

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Abstract

A series of N-1-alkylated 6-benzyluracil-5-carboxylic esters 4a-h were synthesized by reacting imines of 3-oxo-4-phenylbutyrates with N-(chlorocarbonyl) isocyanate. An N-1-(4-methoxybenzyl) group could be removed in a dealkylation reaction to give the ethyl and allyl esters 5a and 5b, respectively. They were N-1-alkylated with chloromethyl ethyl ether or dialloxymethane. Unfortunately no biological activity against HIV-1 and HSV was observed for any of the synthesized compounds.

Key words

HIV-1 - HSV - non-nucleoside reverse transcriptase inhibitors - uracil-5-carboxylic esters - Emivirine

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References

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