Antifolate agents

摘要

2,4-Diamino-5-phenylpyrimidines in the form of the free base or an acid addition salt thereof are provided having the structural formula (I): <IMAGE> I wherein R1 is an alkoxy, aralkoxy or a mono-substituted or disubstituted amino group, R2 is a nitro group, and R3 is an alkyl group. The compounds act as antifolate agents and are useful for therapeutic treatment, for example as antitumour agents, antipsoriatic agents, antibacterial agents, antitrypanosomal agents and antimalarial agents. Pharmaceutical preparations comprising these compounds for administration to mammals, and methods for preparing the compounds, are disclosed. Particularly useful new compounds, especially for antitumour therapy, have the structural formula IA: <IMAGE> IA in which formula IA: n is 1-6; R1 represents hydrogen or alkyl; R4, R5 and R6, which may be identical or different, each represnt hydrogen, alkyl, alkoxy, halo, nitro, perfluoroalkyl, a group of formula -CO2Ra wherein Ra represents hydrogen, alkyl or alkoxyalkyl, or a group of formula -COBRbRc wherein Rb and Rc which may be identical or different each represent alkyl; and R3 represents alkyl.