Add time:07/29/2019         Source:sciencedirect.com

Publisher SummaryThis chapter discusses the structural changes that have been made in each of the above regions of methotrexate (MTX), the synthetic chemical methods used in preparing MTX analogs, and the fascinating structure–activity correlations made possible by the availability of these compounds. Because published biochemical and pharmacological data on MTX analogs are at this point extremely voluminous, the original literature should be consulted for additional details. Several attempts have been made to modify the pyrazine ring in MTX with the aim of gaining insight into the role that this region plays in the biological activity of the molecule. The effects on the biological activity of decreasing the size of the pyrazine ring in MTX and aminopterin (AMT) by one carbon, as in the purine analogs, are investigated.

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