Antimetabolites antitumor agent

The pyrimidine 5-fluorouracil (64) is used extensively in the clinic as an antimetabolite antitumor agent. As a consequence of poor absorption by the oral route, the drug is usually administered by the intravenous route. A rather simple latent ated derivative, tegafur (66), has overcome this limitation by providing good oral absorption. Reaction of 5-fluorouracil with trimethylsilyl chloride in the presence of base gives the disilylated derivative (65). Reaction of this with dihydrofuran (obtained by dehydro-... 

Antimetabolites of nucleic acids as antitumor agents 91YGK989. Artemisinine (3,6,9-trimethyl-9,10h-epidioxyperhydropyrano[4,3,2-y/c] benzoxepin-2-one), a new type of antimalarial drug 92CSR85. 

The three principal classes of cytotoxic agents used in the treatment of cancer all contain carcinogens, for example, Melphalen, a nitrogen mustard, adriamycin, an antitumor antibiotic, and methotrexate, an antimetabolite. Diethylstilbestrol (DES), a drug formerly widely used, has been associated with cancer of the cervix and vagina in the offspring of treated women. 

Polymer (VI) has been shown to have antitumor activity against adenocarcinoma 755, Dunning ascites leukemia. Friend leukemia virus, and Lewis lung carcinoma. In the latter case, polymer (VI) showed activity about equal to that of cyclophosphamide (an alkylating agent) and was more effective than 6-mercaptopurine (an antimetabolite) ( ). The DIVEMA polymer (V) Is also active against some cancer causing viruses such as Friend leukemia, Moloney sarcoma and Rauscher leukemia ( ). 

Cladribine (2-chlorodeoxyadenosine 2-CDA) is a purine nucleoside analog that is resistant to inactivation by adenosine deaminase. The triphosphate form of this agent is incorporated into DNA, resulting in inhibition of DNA synthesis and early chain termination. Cladribine s antitumor activity is unusual for an antimetabolite in that it affects both actively dividing and resting cancer cells. Like fludarabine, cladribine possesses immunosuppressive effects that place patients at risk for serious opportunistic infections. ... 

Contents E.J.Ariens, A.-M.Simonis Design of Bioactive Compounds. -T.J.Bardos Antimetabolites Molecular Approaches for Designing Antiviral and Antitumor Compounds. -T.A.Connors Alkylating Agents. -E.De Clercq Synthetic Interferon Inducers. - C.Woenckhaus Synthesis and Properties of Some New NAD Analogues. 

The ubiquitous distribution of both MTs and stress proteins may be exploited in cancer therapy regimens. MT may serve as an adjunct in cancer chemotherapy (Imura et al. 1991 Cherian et al. 1994). The selective induction of MT by bismuth in noncancer cells protects these cells from harmful side effects of a number of chemotherapeutics, including alkylating agents, antimetabolites, and mitotic inhibitors, but does not interfere with the efficacy of these compounds. Conversely, the presence of MT in tumors may act as a multidrug resistance factor in cancer chemotherapy (Cherian et al. 1994). While the role of stress proteins is not clearly defined, hyperthermia potentiates the antitumor effects of chemotherapeutics and radiotherapy (Nover 1991). 

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