5-Fluorouracil, vinyl monomers

Polymer Synthesis of Vinyl Monomers Having 5-Fluorouracil. . . . 108... 

The first reported vinyl-type monomers of 5-fluorouracil appear to be the carbamoyl derivatives which were made as shown in Equation (1). The vinylcarbamoyl derivative (Ila) has been obtained in 42% yield and readily polymerizes under radical initiation. The pol3nner is active against P388 leukemia but it is not certain whether this is due to activity of the polymer or to a slow release of 5-FU by this polymer in an aqueous system (41-43). The isopropenylcarbamoyl derivative (Ilb) also polymerized under radical conditions but not as well as the vinylcarbamoyl derivative. The allylcarbamoyl derivative (lie) does not appear to polymerize or copolymerize (41). 

III) and vinyl (IV) derivatives of 5-fluorouracil. The acryloyl derivative (III) does appear to form when 5-FU is reacted with acryloyl chloride but this monomer appears to hydrolyze too rapidly to be considered to be of value in a polymeric drug (44). Many attempts were made to prepare the vinyl derivative (IV) via the vinylation reaction (45) under a wide variety of reaction conditions but this was not successful (46). 

Recently Butler, et al have prepared another vinyl-type monomer containing 5-fluorouracil by the reaction of 5-FU with methyl fumaroyl chloride and this is shown below as (V). This monomer hydrolyzes rapidly in water but many of the copolymers hydrolyze more slowly and these polymers show promise as an anti-tumor system (47). Controlled release of 5-FU from various polymeric matrices has also been reported recently (48). 

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