Nucleic acids components and their analogues. LXXIII. A study on benzylation of 6-azauracil

Nováček, A.; Hesoun, D.

doi:10.1135/cccc19653890

Cited by 4 publications

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“…Convenient to our design a recent method for the 1-N-benzylation of 6-azauracil has been published. 45 Improved yields were obtained by silylation of the 2,4-oxo functions of 6-azauracil prior to benzylation as has been done in the synthesis of nucleoside analogues. 46 28…”

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confidence: 99%

Anticoccidial derivatives of 6-azauracil. 1. Enhancement of activity by benzylation of nitrogen-1. Observations on the design of nucleotide analogs in chemotherapy

Mylari¹,

Miller²,

Howes³

et al. 1977

J. Med. Chem.

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Benzylation of 6-azauracil at N-1 (which corresponds to the point of attachment of the ribose phosphate unit in pyrimidine nucleotides) has been found to augment its anticoccidial activity fourfold. The high potency of 1-benzyl-6-azauracil is ascribed to a combination of intrinsic activity, efficient oral absorption, and a moderate rate of excretion. Metabolism experiments using 1-benzyl-6-azauracil labeled with 14C in the heterocycle and (separately) in the side chain showed that, in the drug accounted for, no cleavage had occurred. Additional activity increases were achieved by introducing small, electron-withdrawing substituents in the meta and/or para position(s) of the benzyl group. One of the most active derivaties, 1-(3-cyanobenzyl)-6-azauracil, is about 16 times as potent as 6-azauracil.

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confidence: 99%