Selective Inhibitors of Dihydrofolate Reductase (Nobel Lecture)

Purine and pyrimidine derivatives acting as nucleic base antagonists and inhibitors of dihydrofolate-reductase(DHFR), which is an essential enzyme for nuclei acid synthesis in vivo, have opened up access to the chemotherapy of cancer, particularly leukemia, to immunosuppression, and to the treatment of gout and virus diseases. Examples from the Nobel lectures of Gertrude Elion and George Hitchings are the clinically extremely important antiviral agent acyclovir 1 (purine derivative) and the DHFR inhibitor trimetrexate 2 (pyrimidine derivative).