Showing papers on "Triazene published in 1977"
TL;DR: 4-Amino-2-[2-(piperidin-1-ylazo)phenyl]quinazoline behaves as a masked diazonium compound and decomposes in mineral acids, in acetic acid containing copper-bronze, in hot ethylene glycol, on photolysis in methanol or ethanol, or on reduction.
Abstract: The reactions of anthranilonitrile and 5-bromoanthranilonitrile with sodium hydride in dimethyl sulphoxide yield 4-amino-2-(2-aminophenyl)quinazoline (7) and its dibromo-analogue (8), respectively. Nitrosation of the diamines affords unstable diazonium salts which cyclise to either quinazolino[3,2-c]- or quinazolino[1,2-c]-[1,2,3]benzotriazines. These tetracyclic triazines readily undergo ring opening in the presence of secondary-amines to form the title compounds. 1,3-Bis-(2-cyano-4-bromophenyl)triazene (12) is smoothly transformed into dibromoquinazolines (18) in boiling secondary amines.4-Amino-2-[2-(piperidin-1-ylazo)phenyl]quinazoline (17a) behaves as a masked diazonium compound and decomposes in mineral acids, in acetic acid containing copper-bronze, in hot ethylene glycol, on photolysis in methanol or ethanol, or on reduction. The triazene linkage of (17a) is resistant to alcoholic potassium hydroxide but the 4-aminoquinazoline nucleus is hydrolysed to the corresponding quinazolin-4(3H)-one system. Methylation of (17a) with methyl iodide in tetrahydrofuran affords an N(1) methiodide (29) which is hydrolysed to the corresponding 1-methylquinazolin-4(1H)-one (30) in aqueous alkali. The unusual properties of this and other 1-methylquinazolin-4(1H)-ones can be attributed to their dipolar character. This renders the 1-methyl group liable to removal in acidic conditions.
48 citations
TL;DR: Several 1-aryl-3,3-dimethyltriazene derivatives have been synthesized and tested for their antitumor activity against the TLX5 lymphoma in mice and three p-sulfamoyl derivatives have also been included and proved to be inactive.
Abstract: Several 1-aryl-3,3-dimethyltriazene derivatives have been synthesized and tested for their antitumor activity against the TLX5 lymphoma in mice. These compounds are characterized by the presence of a carbonyl group bound to the benzene nucleus in the para position to the triazene funciton. Three p-sulfamoyl derivatives have also been included and proved to be inactive. Among the carbonyl derivatives compounds 1 and 20, which can be used as reference, cause ILS of about 50%, respectively, at four and three dose levels. Compound 16, the o-nitro-phenylhydrazone of the hydrazide 1, is active at all six dose levels studied. The adduct 19, obtained from the same hydrazide and p-nitrobenzaldehyde, is active at four dose levels, and the ILS values at two optimum doses are significantly greater than those caused by compound 1.
21 citations
20 citations
TL;DR: N1-Acyl derivatives of the tumor inhibitory 4'-(9-acridinylamino)methanesulfonanilide agents act as prodrugs undergoing deacylation to liberate the core agents on incubation with pH 7.5 buffer or mouse blood, and usual metabolic activation of the triazene N-methyl group may make little contribution to antitumor properties in the examples presented.
Abstract: N1-Acyl derivatives of the tumor inhibitory 4'-(9-acridinylamino)methanesulfonanilide agents act as prodrugs undergoing deacylation to liberate the core agents on incubation with pH 7.5 buffer or mouse blood. Against L1210 tumor implanted remotely from the drug administration site, lower acyl derivatives often provide enhanced effects over that obtained with nonacylated precursor alone. In certain homologous series of acyl derivatives, toxicity first increased with increasing lipophilic character, until greater than that of the core agent alone, and then at higher lipophilic levels decreased. Tumor inhibitory properties of the acyl derivatives in such series appeared inversely related to their toxicity. Several 3-(3,3-dialkyl-1-triazeno)acridine-substituted congeners provided excellent L1210 activity. Contrasting with most other tumor-active triazenes, one alkyl group need not be a methyl group of antileukemic activity to be observed. 3-Methyl-3-propyl-1-triazene and 3,3-diethyl-1-trazene analogues had comparable lipophilic-hydrophilic balance, toxicity, and antileukemic effectiveness; usual metabolic activation of the triazene N-methyl group may make little contribution to antitumor properties in the examples presented. Prepared as a nonalkylated triazene analogue, a 3-azidoacridine congener had high L1210 activity.
9 citations
TL;DR: In this paper, aryl radicals are involved in the formation of 2-(18.5%), 3-(49.5%) and 4-(32%) t-butylbiphenyls (total yield 106 mol per 100 mol) on nitrosation of 1,3-diphenyltriazene in tbutylbenzene, and the relative extents of reaction of this nitrosated triazene with benzene and chlorobenzene (excess of an equimolar mixture; ratio 1 : 1.6, respectively).
Abstract: Nitrosation of 1,3-diaryltriazenes (XC6H4·NHN2·C6H6X; X = H, 4-Me, 4-MeO, 4-Cl, 4-NO2, 2-Me, 2-Cl, or 3-Cl) by pentyl nitrite in benzene at 80 °C, and subsequent in situ decomposition of the resulting N-nitroso-1,3-diaryltriazenes, gives biaryls (XC6H4Ph)(54–142 mol per 100 mol of triazene). 1-(4-Chlorophenyl)-3-phenyltriazene gives a mixture of 4-chlorobiphenyl (66 mol per 100 mol) and biphenyl (65 mol per 100 mol). That aryl radicals are involved follows (a) from the formation of 2-(18.5%), 3-(49.5%), and 4-(32%) t-butylbiphenyls (total yield 106 mol per 100 mol) on nitrosation of 1,3-diphenyltriazene in t-butylbenzene, and (b) from the relative extents of reaction of this nitrosated triazene with benzene and chlorobenzene (excess of an equimolar mixture; ratio 1 : 1.6, respectively). Reaction of pentyl nitrite with 1,3-diphenyltriazene in bromotrichloromethane at 15 °C gives a precipitate of benzenediazonium chloride (80 mol per 100 mol). Also formed are bromobenzene (33), chlorobenzene (21), carbon dioxide (10), and pentyl carbanilate (10) mol per 100 mol). At 50 °C the reaction gave chlorobenzene (61) and bromobenzene (49); addition of 1,1-diphenylethene led to an almost complete reversal of these proportions. These results provide another example of anomalous dual halogen abstraction from bromotrichloromethane and support the general mechanism for this type of reaction outlined in the preceding paper.
4 citations
TL;DR: In this paper, a series of N-[(N-nitrosoarylamino) methyl] succinimides were synthesized, disclosing their syn and anti equilibria in a state of solution.
Abstract: We have newly synthesized a series of N-[(N-nitrosoarylamino) methyl] succinimides, disclosing their syn and anti equilibria in a state of solution. It has been found that these nitrosoamines are capable of furnishing aromatic diazotates in basic media. By allowing the generating aromatic diazotates to react in situ, azo-couplings and triazene formations have been provided. The nitrosoamines behaved in acidic media to suffer a migration of the nitroso group similarly to the Fischer-Hepp migration.
4 citations
Patent•
19 Dec 1977TL;DR: A novel triazene compound which upon thermal or photochemical decomposition provides free radicals for polymer initiation and methods using same is described in this paper, where the free radicals are used for polymer synthesis.
Abstract: A novel triazene compound which upon thermal or photochemical decomposition provides free radicals for polymer initiation and methods using same.
3 citations
TL;DR: Oxidation at the α-position of the piperidine ring is an activating step in the development of alkylating activity in 1-(arylazo)piperidines: a mechanism for this process is proposed.
Abstract: Oxidation of 1-(4-chlorophenylazo)piperidine with aqueous potassium permanganate afforded 4-chloroaniline, 1,3-bis-(4-chlorophenyl)triazene, and the oxidised triazenes 1-(4-chlorophenylazo)piperidin-2-one, -4-one, -3-ol, and -4-ol, and 1-(4-chlorophenylazo)-1,2,3,4-tetrahydropyridine. Oxidation of 4-amino-2-[2-(piperidin-1-ylazo)pheny]quinazoline yielded 4-amino-2-(2-aminophenyl)quinazoline and 1-[2-(4-aminoquinazolin-2-yl)phenylazo]piperidin-2-one.Hydrolysis of 1-(4-chlorophenylazo)piperidin-2-one with 0.1 N-potassium hydroxide in the dark yielded 4-chloroaniline and valerolactone. Valerolactone was also identified as an oxidation product from treatment of 4-amino-2-[2-(piperidin-1-ylazo)phenyl]quinazoline and N-nitrosopiperidine with permanganate. Oxidation at the α-position of the piperidine ring is an activating step in the development of alkylating activity in 1-(arylazo)piperidines: a mechanism for this process is proposed.
3 citations
Journal Article•
TL;DR: CD-spectrum of partially inactivated enzyme shows that conformational changes occurred after treatment with diazo compound, which indicates that the mechanism is mediated through triazene.
Abstract: Cathepsin D was inactivated with various diazo compounds at very high concentration. Reaction proceeded maximally at pH 4.5 in the presence of cupric ions. With 3-diazo-indazole and triazene the inactivation was noted also in the absence of cupric ions what indicates that the mechanism is mediated through triazene. CD-spectrum of partially inactivated enzyme shows that conformational changes occurred after treatment with diazo compound.
3 citations
01 Jan 1977
TL;DR: While a large number of derivatives in both groups have been synthesized and evaluated for biological activity, the representatives reported in this chapter are few and are the most interesting ones from both the therapeutic and the theoretical points of view.
Abstract: Hydrazines, but not triazines, have been identified in a small number of biological substances. Those used in cancer chemotherapy are synthetic products, are relatively unstable, and provide biologically active groups on their decomposition and metabolism. The basic moieties of hydrazine, H2N-NH2, and triazene, NH2 N=NH, are substituted with aromatic and aliphatic groups on both ends of their nitrogen bridges; these substituents probably also provide a limited stability to the respective molecules. While a large number of derivatives in both groups have been synthesized and evaluated for biological activity, the representatives reported in this chapter are few, and are the most interesting ones from both the therapeutic and the theoretical points of view.
2 citations
TL;DR: In this paper, a series of N-[(N-nitrosoarylamino) methyl] succinimides were synthesized, disclosing their syn and anti equilibria in a state of solution.
Abstract: We have newly synthesized a series of N-[(N-nitrosoarylamino) methyl] succinimides, disclosing their syn and anti equilibria in a state of solution. It has been found that these nitrosoamines are capable of furnishing aromatic diazotates in basic media. By allowing the generating aromatic diazotates to react in situ, azo-couplings and triazene formations have been provided. The nitrosoamines behaved in acidic media to suffer a migration of the nitroso group similarly to the Fischer-Hepp migration.
TL;DR: Several 1-aryl-3,3-dimethyltriazene derivatives have been synthesized and tested for their antitumor activity against the TLX5 lymphoma in mice as mentioned in this paper.
Abstract: Several 1-aryl-3,3-dimethyltriazene derivatives have been synthesized and tested for their antitumor activity against the TLX5 lymphoma in mice. These compounds are characterized by the presence of a carbonyl group bound to the benzene nucleus in the para position to the triazene funciton. Three p-sulfamoyl derivatives have also been included and proved to be inactive. Among the carbonyl derivatives compounds 1 and 20, which can be used as reference, cause ILS of about 50%, respectively, at four and three dose levels. Compound 16, the o-nitro-phenylhydrazone of the hydrazide 1, is active at all six dose levels studied. The adduct 19, obtained from the same hydrazide and p-nitrobenzaldehyde, is active at four dose levels, and the ILS values at two optimum doses are significantly greater than those caused by compound 1.
TL;DR: In this article, a series of acyl derivatives of tumor inhibitory 4'-9-acridinylamino)methanesulfonanilide agents were evaluated against L1210 tumor implanted remotely from the drug administration site.
Abstract: N1-Acyl derivatives of the tumor inhibitory 4'-(9-acridinylamino)methanesulfonanilide agents act as prodrugs undergoing deacylation to liberate the core agents on incubation with pH 7.5 buffer or mouse blood. Against L1210 tumor implanted remotely from the drug administration site, lower acyl derivatives often provide enhanced effects over that obtained with nonacylated precursor alone. In certain homologous series of acyl derivatives, toxicity first increased with increasing lipophilic character, until greater than that of the core agent alone, and then at higher lipophilic levels decreased. Tumor inhibitory properties of the acyl derivatives in such series appeared inversely related to their toxicity. Several 3-(3,3-dialkyl-1-triazeno)acridine-substituted congeners provided excellent L1210 activity. Contrasting with most other tumor-active triazenes, one alkyl group need not be a methyl group of antileukemic activity to be observed. 3-Methyl-3-propyl-1-triazene and 3,3-diethyl-1-trazene analogues had comparable lipophilic-hydrophilic balance, toxicity, and antileukemic effectiveness; usual metabolic activation of the triazene N-methyl group may make little contribution to antitumor properties in the examples presented. Prepared as a nonalkylated triazene analogue, a 3-azidoacridine congener had high L1210 activity.