Articles liés à Triazenes: Chemical, Biological, and Clinical Aspects

Triazenes: Chemical, Biological, and Clinical Aspects - Couverture souple

 
9781461367109: Triazenes: Chemical, Biological, and Clinical Aspects
Couverture souple
ISBN 10 : 1461367107 ISBN 13 : 9781461367109
Editeur : Springer, 2012

Synopsis

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.

Les informations fournies dans la section « Synopsis » peuvent faire référence à une autre édition de ce titre.

À propos de la quatrième de couverture

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.

Les informations fournies dans la section « A propos du livre » peuvent faire référence à une autre édition de ce titre.

Éditeur
Springer
Date d'édition
2012
Langue
anglais
ISBN 10 
1461367107
ISBN 13 
9781461367109
Reliure
Broché
Nombre de pages
227
Éditeur
Giraldi Tullio, Connors Thomas, Cartei Giuseppe
Coordonnées du fabricant
Springer Nature Customer Service Center GmbH
ProductSafety@springernature.com

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