Chemotherapy pyrimidine analogs

Why then, since such an abundance of metabolic inhibitors is available, do so few of them find practical application Examples are the folic acid reductase inhibitors, such as aminopterin, the purine and pyrimidine analogs used as cytostatics in cancer chemotherapy and known for their high toxicity in a wide variety of species, and the organic phosphates and carbamates used as insecticides but also highly toxic to mammals. Lack of selectivity in the action of metabolic inhibitors is inherent in their mechanism of action due to the universality of biochemical processes and principles throughout nature. Selectivity in action requires species differences in biochemistry. For the antivitamins, for instance, there is not only a lack of species differences in action in addition, the fact that vitamins often serve as cofactors for a variety of enzymes is a serious drawback to endeavors to obtain agents with species-selective action. 

Research in antiviral chemotherapy started around early 1950 s when the search for anticancer drugs revealed several new compounds that inhibit viral DNA synthesis, e.g., the pyrimidine analog idoxuridine which was... 

Hitchings G, Elion G (1967) Mechanisms of action of purine and pyrimidine analogs. In Brodsky I, Kahn S, Moyer J et al (eds) Cancer chemotherapy I. Grune and Stratton, New York, NY, p 26... 

The diazines (pyridazine, pyrimidine, and pyrazine) are six-membered aromatic heterocycles that have two nitrogens in the ring. Cytosine, thymine, and uracil are derivatives of pyrimidine that are important bases in nucleic acids (DNA and RNA). Heterocyclic analogs of the aromatic hydrocarbon naphthalene include pteridines, which have four nitrogens in the rings. Naturally occurring pteridine derivatives include xanthopterin (a pigment) and folic acid (a vitamin). Methotrexate is a pteridine used in cancer chemotherapy. 

PRPP was also utilized in the formation of 5 -ribonucleotides from naturally occurring purine and pyrimidine bases (73, 80, 83, 84) and from synthetically prepared analogs (86). It was required in purine biosynthesis (86) and its precise role will be described below. PRPP also served as a substrate in the de novo synthesis of DPN (87). Its ability to condense with purine analogs to form analogs of 5 -ribonucleotides suggests many possibilities for fundamental studies of cancer chemotherapy. 

The utility of pyrimidine and purine analogs in cancer chemotherapy (e.g. 6-mercaptopurine, 5-fluorouracil, arabinosyl cytosine) serves as a continued stimulus for the preparation of new compounds of this type. Among these,3-deaza-uridine [l-(j3-p-ribofuranosyl)-4-hydroxy-2-pyridone] was markedly active... 

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