70346-60-0

Upstream product

• 50-00-0 formaldehyd 
• 99-92-3 p-aminobenzophenone 
• 74-89-5 methylamine 
• 90476-15-6 C₁₇H₁₇N₃O₃ 
• 350-47-0 1-(4-acetylphenyl)diazonium tetrafluoroborate 
• 3283-79-2 4-acetylphenyldiazonium chloride 

Downstream Products

• 67-56-1 methanol 
• 99-92-3 p-aminobenzophenone 
• 90476-15-6 1-p-acetylphenyl-3-methyl-3-benzoyloxymethyltriazene 
• 90476-20-3 1-p-acetylphenyl-3-methyl-3-methoxymethyltriazene 
• 90476-11-2 1-p-acetylphenyl-3-methyl-3-acetoxymethyltriazene 
• 51029-21-1 1-(4-acetylphenyl)-3-methyltriazene 

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.

Triazene Drug Metabolites. Part 4. Kinetics and Mechanism of the Decomposition of 1-Aryl-3-benzoyloxymethyl-3-methyltriazenes in Mixed Aqueous-Organic Solvents

Kinetic studies for the hydrolysis of 1-aryl-3-benzoyloxymethyl-3-methyltriazenes to 1-aryl-3-hydroxymethyl-3-methyltriazenes in mixed aqueous-organic media are reported.Reactions are first-order in the benzoyloxymethyltriazene, and are independent of pH above pH 8.Below pH 8, specific acid catalysis is observed.No nucleophilic catalysis is detected at any pH.The observed first-order rate constants, kobs, vary with the substituent in both the 1-aryl and benzoyl rings.Hammett ? values of 1.28 and 1.41 are obtained for substituents in the benzoyl group in 50percent MeCN-H2O and 60percent dioxane-H2O respectively.A Hammett ρ value of -1.84 is obtained in 50percent MeCN-H2O for substituents in the 1-aryl ring.Observed first-order rate constants also vary with the composition of aqueous dioxane mixtures and a linear correlation between log kobs and the Grunwald-Winstein Y parameter is found to give a slope of 0.99.The solvent deuterium isotope effect, kH2O/kD2O, is 1.26 for the 4-methoxybenzoyl derivative.Values of the activation parameters are ΔH(excit.) ca. 80 kJ mol-1 and ΔS(excit.) ca. -5 J K-1 mol-1.The data are best interpreted in terms of a unimolecular ionisation of the benzoyloxymethyltriazene to form a iminium cation and a benzoate anion.Hydroxymethyltriazene formation results from the capture of the intermediate iminium ion by water.Consistent with this mechanism, a common ion effect of the benzoate anion is observed, and the benzoate ion is ca. 75 times more effective than water at trapping the iminium ion.

OPEN-CHAIN NITROGEN COMPOUNDS. PART VI. THE FORMATION OF BIS(1-ARYL-3-METHYLTRIAZEN-3-YLMETHYL) METHYLAMINES IN THE REACTION OF DIAZONIUM IONS WITH MIXTURES OF FORMALDEHYDE AND METHYLAMINE

The synthesis of a series of N,N-bis(1-aryl-3-methyltriazen-3-ylmethyl) methylamines from coupling diazonium salts with mixtures of methylamine and formaldehyde is described.These novel bis-triazenes, or heptazanonadienes, have significant anti-tumour activity against the TLX5 lymphoma in mouse.The mechanism of formation of these triazenes is discussed with reference to the implication to the presumed equilibria taking place in the methylamine/formaldehyde solution.The formation of the bis-triazene is usually accompanied by the formation of a 3-hydroxymethyltriazene, and it has been shown that the hydroxymethyltriazene can be transformed into the bis-triazene.The proportions of the two products are strongly influenced by the relative amounts of methylamine and formaldehyde.Coupling the p-bromobenzenediazonium salt to a 1:1 methylamine/formaldehyde mixture affords mainly the bis-triazene, whereas a 1:50 mixture gives almost totally the hydroxymethyl triazene.These results suggest that the two triazenes arise from diazonium coupling to different species in the amine/formaldehyde mixture; this hypothesis is supported by the formation of identical product mixtures from coupling the diazonium ion with (a) a 1:1 MeNH2/CH2O mixture, and (b) the cyclic trimer of the carbinolamine MeNHCH2OH, and by the identification of a minor product from the reaction of p-chlorobenzenediazonium fluoroborate with MeNH2/CH2O as bis(1-p-chlorophenyl-3-methyltriazen-3-yl) methane.

Studies of the mode of action of antitumor triazenes and triazines. 6. 1-Aryl-3-(hydroxymethyl)-3-methyltriazenes: Synthesis, chemistry, and antitumor properties

1-Aryl-3-(hydroxymethyl)-3-alkyltriazenes [ArN=NN(CH3)CH2OH] have been synthesized by diazonium coupling to the carbinolamine (RNHCH2OH), generated in situ from the alkylamine and formaldehyde mixtures. The (hydroxymethyl)triazene structure has been confirmed by IR, NMR, and mass spectral analysis and also by the preparation of a crystalline benzoate derivative. The mass spectra of the (hydroxymethyl)triazenes suggest that they fragment by loss of formaldehyde to give the methyltriazene, which is also the product of hydrolysis in solution. The degradation of the (hydroxymethyl)triazenes in solution has been followed by UV spectroscopy and by HPLC analysis, and the half-lives were determined under a variety of conditions. The half-lives of the corresponding methyl- and (hydroxymethyl)triazenes are very similar. Both methyl- and (hydroxymethyl)triazenes decompose on silica plates during TLC analysis to give products consistent with known diazo-migration reactions. The (hydroxymethyl)triazenes have pronounced antitumor activity against the TLX5 tumor in vivo; in vivo-in vitro bioassay experiments suggest that the (hydroxymethyl)triazenes exert their in vivo antitumor activity via the degradation product, the alkyltriazene.

Triazenes: A Reinvestigation of the Coupling Reaction between Aryldiazonium Ions and Methylamine/Formaldehyde Mixtures

Aryldiazonium fluoroborates react with methylamine/formaldehyde mixtures to give bismethylamines rather than 1-aryl-3-hydroxymethyl-3-methyltriazenes as previously reported.Aryldiazonium chlorides react with methylamin