73779-15-4Relevant articles and documents
Targeting gliomas with triazene-based hybrids: Structure-activity relationship, mechanistic study and stability
Braga, Cláudia,Vaz, Ana R.,Oliveira, M. Concei??o,Matilde Marques,Moreira, Rui,Brites, Dora,Perry, Maria J.
, p. 16 - 25 (2019/04/04)
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.
Triazene Drug Metabolites. Part 4. Kinetics and Mechanism of the Decomposition of 1-Aryl-3-benzoyloxymethyl-3-methyltriazenes in Mixed Aqueous-Organic Solvents
Iley, James N.,Moreira, Rui,Rosa, Eduarda
, p. 1503 - 1508 (2007/10/02)
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
Manning, Hartford W.,Hemens, Chantal M.,LaFrance, Ronald J.,Tang, York,Vaughan, Keith
, p. 749 - 754 (2007/10/02)
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.
