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| Language | English |
| Format | PDF (Premium Digital) |
| Ownership | Permanent download — yours forever |
Triazenes by Tullio Giraldi
More than 25 years have elapsed since the development of the seminal idea which led to the synthesis of dimethyl triazenes as antitumor agents. The original suggestion of Shealy et ale was to use 4-imidazone-carboxarnide as the carrier of a nitro- gen-containing cytotoxic function. 5-diazoimidazole-4-carbox- amide (diazo-IC) was synthesized and tested in mice as a potential inhibitor of de novo purine biosynthesis. Its lack of antitumor action was attributed to its polarity and to the resulting poor uptake of this hydrophilic chemical. Diazo-IC was then coupled with dimethylamine, yielding 5, (3,3-dimethyl- l-triazeno)imidazole-4-carboxamide) (DTIC) with the intention of obtaining a less polar and more lipophil c prod rug which might release diazo-IC intracellularly. Preliminary tests showed that DTIC had good antiumor activity in experimental systems. Further tests demonstrated a broad spectrum of action against rodent tumors, and clinical trials indicated activity against human malignancies. Subsequent clinical use of DTIC has demonstrated its usefulness against malignant melanoma, for which it is currently the drug of choice, and its effective- ness in combination chemotherapy in the treatment of other human cancers. Because of its antitumor activity the mechan- ism of action of DTIC has been investigated in some detail. The original rationale for its development, that is, the hydrolysis in vivo to diazo-IC, has been shown not to be in- volved in th-e-mechansims of action. DTIC requires metabolic acti- vation before it exerts its biological effects.| SKU | NLS9781461367109 |
|---|---|
| ISBN 13 | 9781461367109 |
| ISBN 10 | 1461367107 |
| Author | Tullio Giraldi |
| Condition | New |
| Binding Type | Paperback |
| Publisher | Springer-Verlag New York Inc. |
| Year published | 2012-10-17 |
| Number of pages | 227 |
| Cover note | Book picture is for illustrative purposes only, actual binding, cover or edition may vary. |
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