98225-08-2Relevant academic research and scientific papers
Nucleoside Analogues. Part 2. Further Molecular Combinations of (5-Substituted) Uracil and N-(2-Chloroethyl)-N-nitrosourea Residues as Anticancer Agents
McCormick, Joan E.,McElhinney, R. Stanley
, p. 93 - 100 (2007/10/02)
To assess the contribution of 5-fluoroacil (5-FU) to the antitumour activity observed in B.3839 (1), the original molecular combination of 5-FU and N-(2-chloroethyl)-N-nitrosourea residues, the antimetabolite has been replaced by thymine and by uracil.The pyrimidine 5-substituent influenced the ratio of N1:N3 seco-nucleosides formed at the outset of the synthesis, and later the production of bicyclic bases by intramolecular addition across the 5,6-double bond.To provide drugs from which 5-FU would be cleaved more readily than from B.3839, first the antimetabolite has been attached at a different point (N3 instead of N1) although the intermediates proved more difficult to crystallise; and secondly, the methylthio group attached to the 'anomeric' carbon has been replaced by methylsulphinyl and by alkoxy.Investigation of alternative synthetic sequences confirmed that alkoxy groups had to be incorporated at an early stage, and, since they were sensitive to HBr, base-catalysed isomerisation of the bicyclic bases was necessary, best yields being obtained with the trifluoroacetyl derivatives.N3-Substituted uracil derivatives with alkoxy groups could be prepared, but not the 5-fluoro analogues.
