Chemotherapy folic acid analogues

During the 1980s and 1990s the role of folic acid analogues, especially methotrexate (MTX) (422), in cancer chemotherapy has been intensively studied enzyme dihydrofolate reductase (DHFR) has been the primary target of this effort. The introduction of 10-ethyl-10-deazaaminopterin (10-EDAM) (423), piritrexim (PTX) (424) and trimetrexate (TMX) (425) into clinical trials attests to the continued interest in this field <87MI 718-06). 

A search for antimetabolites, i.e. analogues of essential metabolites that might displace the latter in vital processes, was proposed as a rational approach to the discovery of antibacterial agents, but it has had little success other than the achievements in the folic acid field (Section 1.06.6). Substances that resemble the components of nucleic acids have, however, had considerable success in the chemotherapy of cancer and of some virus diseases and in the suppression of the immune response. They may act by becoming incorporated in false nucleic acids or by blocking the synthesis of nucleic acids, nucleotides, nucleosides or of the pyrimidine and purine bases cytosine (88), thymine (89 R = Me), adenine (90) and guanine (91 X = CH). The simplest antimetabolites are analogues of these bases. 

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