40643-38-7

Usage

InChI:InChI=1/C9H11N3O2/c1-10-12-11-8-5-3-7(4-6-8)9(13)14-2/h3-6H,1-2H3,(H,10,11)

Upstream product

• 67-56-1 methanol 
• 69467-93-2 1--3-(hydroxymethyl)-3-methyltriazene 
• 90476-07-6 1-p-methoxycarbonylphenyl-3-acetoxymethyl-3-methyltriazene 
• 619-45-4 4-methoxycarbonyl aniline 

Downstream Products

• 619-45-4 4-methoxycarbonyl aniline 

Relevant academic research and scientific papers

Targeting gliomas with triazene-based hybrids: Structure-activity relationship, mechanistic study and stability

Herein we report novel hybrid compounds based on valproic acid and DNA-alkylating triazene moieties, 1, with therapeutic potential for glioblastoma multiforme chemotherapy. We identified hybrid compounds 1d and 1e to be remarkably more potent against glioma and more efficient in decreasing invasive cell properties than temozolomide and endowed with chemical and plasma stability. In contrast to temozolomide, which undergoes hydrolysis to release an alkylating metabolite, the valproate hybrids showed a low potential to alkylate DNA. Key physicochemical properties align for optimal CNS penetration, highlighting the potential of these effective triazene based-hybrids for enhanced anticancer chemotherapy.

The selective cytotoxicity of new triazene compounds to human melanoma cells

Metastatic melanoma still remains one the most difficult cancers to overcome. The aim of our research was the design of anti-tumour triazene compounds 3 for application to a melanoma-specific therapy. The strategy exploits the unique enzyme pathway of melanin biosynthesis for conversion of non-toxic prodrugs into toxic drugs in the melanoma cell. The compounds 3 were designed by coupling two active moieties, the alkylating triazenes and different tyrosinase substrates. All compounds 3 revealed to be chemically stable in isotonic phosphate buffer (PBS) at physiologic pH (t??≥?48?h), and most of them showed to be slowly hydrolysed in human plasma (1.5?≤?t? (h)?≤?161). Compounds 3c–n revealed to be excellent tyrosinase substrates (0.74?≤?t? (min)?≤?6) with the best tyrosinase substrate 3l releasing MMT 45?s after tyrosinase activation. Structure-activity relationship studies allowed the identification of the better structural features for enzyme affinity. Furthermore, the derivatives 3l and 3m showed cell selectivity with significant cytotoxic effects (IC50 values of 46–65?μM) against melanoma cell lines with tyrosinase overexpression MNT-1 and B16F10.

Synthesis and evaluation of N-acylamino acids derivatives of triazenes. Activation by tyrosinase in human melanoma cell lines

In this research work we report the synthesis of a new series of triazene prodrugs designed for Melanocyte-Directed Enzyme Prodrug Therapy (MDEPT). These compounds are derived from the N-acyltyrosine amino acid - a good enzyme substrate for the tyrosinase enzyme, which is significantly overexpressed in melanoma cells. We analysed their chemical stability and plasma enzymatic hydrolysis, and we also evaluated the release of the antitumoral drug in the presence of the tyrosinase. Subsequently, we performed the evaluation of the prodrug cytotoxicity in melanoma cell lines with different levels of tyrosinase activity. Prodrug 5c showed the highest cytotoxicity against melanoma cell lines, and this effect correlated well with the tyrosinase activity suggesting that prodrug cytotoxicity is tyrosinase-dependent.

Kinetic Study of the Solvolysis Reactions of 1-Aryl-3-acetoxymethyl-3-alkyltriazenes: Evidence for Iminium Ion Intermediates and the SN1 Mechanism

The first-order rate constants of the reactions of acetoxymethyltriazenes with nucleophiles have been measured.Acetoxymethyltriazenes undergo hydrolysis in phosphate buffer to give the corresponding arylamines, presumably via the hydroxymethyl- and monomethyl-triazenes.The acetoxymethyltriazenes undergo solvolysis in alcohols and in mixtures of alcohols and other solvents; the rate of solvolysis has been correlated with the Grunwald-Winstein parameter (Y) for solvent ionising power, thus supporting the hypothesis of an SN1 mechanism and the intermediate formation of iminium ions during the solvolysis.The hypothesis is further supported by the non-common-ion effect; the presence of lithium chloride in the solvent greatly increases the rate of reaction, whereas lithium acetate causes a slight decrease in rate, attributable to a common-ion effect.Reaction of the acetoxymethyltriazene with sodium azide in aqueous acetone affords the α-azidomethyltriazene (a new type of triazene not previously reported) and provides supporting evidence for the iminium ion hypothesis.On the other hand, the acetoxymethyltriazene did not react with neat ethanethiol, providing further evidence for an SN1 mechanism; and SN2 reaction would be expected to proceed more quickly in the thiol than in the alcohol.It is shown that hydroxymethyltriazenes do not react via iminium ions and that functionalisation to a derivative such as the acetate is necessary for iminium ion generation.The implications of these results for the metabolism of xenobiotic N-alkyl compounds are discussed.

Substituent Effects on 13C and 15N Chemical Shifts in Triazenes Studied by Principal Components Multivariate Data Analysis

Principal components analysis was applied to the 13C and 15N chemical shift data on a series of fifteen 1-(para-substituted-phenyl)-3-acetyl-3-methyltriazenes.It was found that the halogen-substituted triazenes formed a class, based on substituent effects, which was different from the remaining eleven triazenes.A one-component model described the halogen class, whereas a two-component model was necessary for a description of the second class.In the second class, substituent tended to cluster to form groups depending on their electronic character.