527-73-1Relevant articles and documents
Evaluation of (S)- and (R)-misonidazole as GPX inhibitors: Synthesis, characterization including circular dichroism and in vitro testing on bovine GPx-1
Wilde, Felix,Chamseddin, Chamseddin,Lemmerhirt, Heidi,Bednarski, Patrick J.,Jira, Thomas,Link, Andreas
, p. 153 - 160 (2014)
Racemic misonidazole, a radiosensitizer formally used in radiation therapy of cancer and to date still applied, was once reported to exhibit strong inhibitory effects on mouse glutathione peroxidases (GPX). This appeared to qualify misonidazole as a lead structure for the development of novel GPX inhibitors to cause oxidative stress in chemotherapy-resistant tumors. A unique feature of misonidazole as an inhibitor of GPX is the absence of a thiol functionality. Therefore, it was expected to selectively target inhibition devoid of promiscuous interactions with cations and sulfhydryl groups. We synthesized the isomers of misonidazole and analyzed the ability of chiroptical high-performance liquid chromatography (HPLC) to identify the particular enantiomers. Due to the chiral pool synthesis, the assignment of the correct configuration could be verified. Finally, we evaluated both isomers for their inhibitory activities on bovine erythrocyte GPx-1, which is 87% homologous to the human enzyme. Despite the previously reported inhibition of racemic misonidazole on the less homologous mouse GPx-1, we did not find any significant inhibitory activity on the bovine enzyme for either isomer. Though misonidazole appears unlikely to be an inhibitor of human GPx-1 activity, we still spotlight misonidazole as a promising fragment-like lead structure in general. The (S)- and (R)-isomers of misonidazole were synthesized and analyzed for their inhibitory activities on bovine erythrocyte GPx-1, which is 87% homologous to the human enzyme. Although misonidazole was found to be not likely to be an inhibitor of human GPx-1 activity, misonidazole is still spotlighted as a promising fragment-like lead structure in general.
Preparation method of 2-nitroimidazole
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Paragraph 0029; 0031; 0032; 0034; 0035; 0037, (2020/05/01)
The invention discloses a preparation method of 2-nitroimidazole. The method comprises the following steps: carrying out selective bromination on imidazole as an initial raw material in an imidazole ionic liquid, introducing bromine atoms to the 2-site of the imidazole ring to generate 2-bromoimidazole, and carrying out a nitrosation reaction under the action of a catalyst to obtain 2-nitroimidazole. Based on the defects of difficultly available and expensive raw material 2-aminoimidazole sulfate, risk in use of fluoroboric acid, high copper sulfate consumption and environmental pollution caused by high copper sulfate consumption in the prior art, a new synthesis route is developed, wherein the raw materials are easy to obtain, the steps are short, the cost is low, and the method is environmentally friendly.
Synthesis and Antitrypanosomal Activity of 1,4-Disubstituted Triazole Compounds Based on a 2-Nitroimidazole Scaffold: a Structure-Activity Relationship Study
Assun??o, Elvis L. F.,Carvalho, Diego B.,das Neves, Amarith R.,Kawasoko Shiguemotto, Cristiane Y.,Portapilla, Gisele B.,de Albuquerque, Sergio,Baroni, Adriano C. M.
, p. 2019 - 2028 (2020/09/21)
Chagas disease affects 6–8 million people worldwide, remaining a public health concern. Toxicity, several adverse effects and inefficiency in the chronic stage of the disease are the major challenges regarding the available treatment protocols. This work involved the synthesis of twenty-two 1,4-disubstituted-1,2,3-triazole analogues of benznidazole (BZN), by using a click chemistry strategy. Analogues were obtained in moderate to good yields (40-97 %). Antitrypanosomal activity was evaluated against the amastigote forms of Trypanosoma cruzi. Compound 8 a (4-(2-nitro-1H-imidazol-1-yl)methyl)-1-phenyl-1H-1,2,3-triazole) without substituents on phenyl ring showed similar biological activity to BZN (IC50=3.0 μM, SI>65.3), with an IC50=3.1 μM and SI>64.5. Compound 8 o (3,4-di-OCH3?Ph) with IC50 = 0.65 μM was five-fold more active than BZN, and showed an excellent selectivity index (SI>307.7). Compound 8 v (3-NO2, 4-CH3?Ph) with IC50=1.2 μM and relevant SI>166.7, also exhibited higher activity than BZN. SAR analysis exhibited a pattern regarding antitrypanosomal activity relative to BZN, in compounds with electron-withdrawing groups (Hammett σ+) at position 3, and electron-donating groups (Hammett σ-) at position 4, as observed in 8 o and 8 v. Further research might explore in vivo antitrypanosomal activity of promising analogues 8 a, 8 o, and 8 v. Overall, this study indicates that approaches such as the bioisosteric replacement of amide group by 1,2,3-triazole ring, the use of click chemistry as a synthesis strategy, and design tools like Craig-plot and Topliss tree are promising alternatives to drug discovery.
Synthesis and antiproliferatory activity of ruthenium complexes containing N-heterocyclic carboxylates
Kennedy, David C.,James, Brian R.
, p. 32 - 36 (2017/03/11)
Solvates of the complexes Ru2Cl(pic)4(EtOH) (2), Ru(Im-CO2)3 (3), and Ru(Im-CO2)(Im-CO2H)Cl2 (4), were synthesized from reaction of RuCl3·3H2O or K3[RuCl6] with the N-heterocyclic carboxylic acids pyridine-2-carboxylic acid (picolinic acid, Hpic), and imidazole-4-carboxylic acid (Im-CO2H). Crystals of 2–4 could not be grown and hence characterization was done by elemental analysis, NMR, IR, and conductivity data; 2 and 4 were tested for antiproliferatory activity in vitro against a human breast cancer cell line, but were less active than, for example, Ru complexes containing bis-imidazole or 4,4′-biimidazole that we studied previously [see Can. J. Chem. 89 (2011) 948]. Preliminary work with a third potential ligand, 3-nitro-1,2,4-triazole-5-carboxylic acid (abbreviated HCANT), and other nitro heterocyclic compounds is also presented.
METHOD FOR MANUFACTURING RADIOACTIVE HALOGEN LABELED COMPOUND
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Paragraph 0039; 0040, (2016/12/22)
PROBLEM TO BE SOLVED: To provide means for efficiently manufacturing a radioactive halogen labeled compound. SOLUTION: There is provided a method for manufacturing a radioactive halogen labeled compound represented by the formula: Sub-X, where Sub represents a substrate and X represents a radioactive halogen atom, and including (1) a process of reacting a high molecular compound containing a substrate and a radioactive halogenated ion under a condition where a phase transfer catalyst exists, (2) a process of binding a byproduct represented by a formula: Sub-OH, where Sub represents a substrate, isolating from the high molecular compound and a compound having an isocyanate group, (3) a process of removing a byproduct bound with the compound having the isocyanate group, and (4) a process of obtaining the radioactive halogen labeled compound from a reaction product of the high molecular compound and the radioactive halogenated ion. COPYRIGHT: (C)2015,JPOandINPIT
A green and facile approach for synthesis of nitro heteroaromatics in water
Zhao, Xiu X.,Zhang, Ji C.,Li, Sheng H.,Yang, Qing P.,Li, Yu C.,Pang, Si P.
, p. 886 - 890 (2014/08/05)
A convenient and green method for the oxidation of nitrogen-rich heterocyclic amines to nitro-substituted heteroaromatics using potassium peroxymonosulfate (2KHSO5·KHSO4·K 2SO4, Oxone) in water was developed. This method has several advantages over previous methods: operational simplicity, safety, inexpensive reagents, the use of H2O as the sole solvent, and mild conditions. The utility of the present oxidative system was demonstrated by the synthesis of the important energetic compounds 3,4,5-trinitro-1H-pyrazole (TNP) and 5-amino-3-nitro-1H-1,2,4-triazole (ANTA).
Synthesis of a hypoxia-targeted conjugate of the cardioprotective agent 3′,4′-dihydroxyflavonol and evaluation of its ability to reduce ischaemia/reperfusion injury
Yap, Suwan,Woodman, Owen L.,Crack, Peter J.,Williams, Spencer J.
supporting information; experimental part, p. 5102 - 5106 (2011/10/09)
3′,4′-Dihydroxyflavonol (DiOHF) is a cardioprotective flavonol that reduces injury associated with myocardial ischaemia and reperfusion. We hypothesized that the efficacy of DiOHF could be enhanced through its targeting to hypoxic regions of partial reperfusion. Copper(I)-catalyzed ligation of an azide-modified DiOHF analogue to 2-propargyl-nitroimidazole afforded a DiOHF-nitroimidazole conjugate (DiOHF-NIm). When incubated with Con8 cells under normoxic conditions DiOHF-NIm could be detected in both the culture supernatant and cell lysate, whereas under hypoxic conditions it was present in substantially reduced amounts consistent with its selective metabolism under hypoxia. DiOHF-NIm possessed antioxidant activity comparable to DiOHF through scavenging of superoxide produced by NADPH/NADPH oxidase, but had significantly attenuated vasorelaxant activity. DiOHF-NIm treatment significantly reduced lactate dehydrogenase release following ischaemia/reperfusion in hindlimbs of anaesthetized rats (p 0.05), to a level similar to DiOHF treatment but also at earlier time points. DiOHF-NIm significantly reduced levels of myeloperoxidase (p 0.05), a biomarker of neutrophil accumulation, whereas the reduction afforded by DiOHF was not significant. DiOHF-NIm therefore represents a promising potential therapeutic for ischaemia/reperfusion injury.
New Synthesis of 2-Nitroimidazoles
Davis, Dwight P.,Kirk, Kenneth L.,Cohen, Louis A.
, p. 253 - 256 (2007/10/02)
1-Triphenylmethylimidazoles are treated with n-butyllithium in tetrahydrofuran at 0 deg C to form the 2-lithio derivatives.The latter species react with n-propyl nitrate to give 1-trityl-2-nitroimidazoles which, after acid hydrolysis, provide the correspondine 2-nitroimidazoles. 2-Nitroimidazole was obtained from imidazole from overall yields of 27-35percent; 4-methyl-2-nitroimidazole was obtained in 40percent overall yield from 4-methylimidazole.Imidazole-4,5-dicarboxylic acid was converted, in several steps, to 1-tritylimidazole-4-methanil, and the latter compound was transformed into 2-nitroimidazole-4-methanol in an overall yield of 18percent.Protection of the hydroxymethyl function was found to be unnecessary during carbanion formation and nitration.Attempts to nitrate 1-methylimidazole or 1-methoxymethylimidazole by the same procedure failed.
Mass Spectrometry of Nitroazoles. 3-Ortho Effects: The loss of OH. and H2O from Methyl Substituted Nitrodiazoles
Luijten, W. C. M. M.,Thuijl, J. van
, p. 299 - 303 (2007/10/02)
Methyl substituted nitrodiazoles which have the substituents at adjacent positions in the ring are subject to several ortho effects.Deuterium labelling of the methyl group and the mobile N-bonded hydrogen show that the loss of OH. originates from the substituents.In some cases the N-bonded hydrogen atom participates also in the loss of OH. and of H2O.
