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亚硝基-烯(Nitroso-ene)反应的研究进展 被引量:1
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作者 黄莎华 霍华兴 +1 位作者 李文华 洪然 《有机化学》 SCIE CAS CSCD 北大核心 2012年第10期1776-1791,共16页
烯丙基胺类化合物是有机化学中的重要合成中间体,亚硝基-烯(nitroso-ene)反应是合成这类化合物最为高效的方法之一.在一些天然产物和药物分子的全合成中,亚硝基-烯反应也往往作为关键步骤.这篇综述主要介绍了亚硝基–烯反应的发展、应... 烯丙基胺类化合物是有机化学中的重要合成中间体,亚硝基-烯(nitroso-ene)反应是合成这类化合物最为高效的方法之一.在一些天然产物和药物分子的全合成中,亚硝基-烯反应也往往作为关键步骤.这篇综述主要介绍了亚硝基–烯反应的发展、应用以及机理研究方面的进展. 展开更多
关键词 烯丙基胺 亚硝基化合物 亚硝基-烯(nitroso-ene)反应 天然产物合成
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Nitroso-R光度法检测湿法炼锌净化渣中的Co(Ⅱ)
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作者 麦蚁茜 黄晖 +3 位作者 何雨 庄大玲 付午杰 张启卫 《广州化工》 CAS 2014年第6期99-101,107,共4页
湿法炼锌净化渣中的钻是重要的二次资源,测定钻含量是钻合理回收的基本条件。在pH=7.5时,亚硝基R盐与co(II)形成络合物并被氧化形成Co(Ⅲ)的稳定络合物,并以浓硫酸破坏样品中干扰离子的络合物,消除干扰。在波长入=522nm检测,... 湿法炼锌净化渣中的钻是重要的二次资源,测定钻含量是钻合理回收的基本条件。在pH=7.5时,亚硝基R盐与co(II)形成络合物并被氧化形成Co(Ⅲ)的稳定络合物,并以浓硫酸破坏样品中干扰离子的络合物,消除干扰。在波长入=522nm检测,检测限为0.0274μg/mL(n=6),在0—5.0μg/mL范围内符合比尔定律。方法用于检测样品中的钴含量为2.80%,ICP检测结果为2.89%,结果满意。 展开更多
关键词 CO(II) nitroso—RSalt 分光光度法
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Improved Studies on the Synthesis,Characterization and Crystal Structure of 2,2-Dimethyl-5-nitro-5-nitroso-1,3-dioxane 被引量:1
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作者 张家荣 毕福强 +5 位作者 王伯周 张俊林 王民昌 贾思媛 霍欢 李祥志 《Chinese Journal of Structural Chemistry》 SCIE CAS CSCD 2017年第3期401-408,共8页
The synthetic process for 2,2-dimethyl-5-nitro-5-nitroso-1,3-dioxane(DMNNDO) was improved by using tri(hydroxymethyl)nitromethane and acetone as starting materials through a "one-pot" method combined with alkali... The synthetic process for 2,2-dimethyl-5-nitro-5-nitroso-1,3-dioxane(DMNNDO) was improved by using tri(hydroxymethyl)nitromethane and acetone as starting materials through a "one-pot" method combined with alkaline hydrolysis and nitrosation reactions. The yield of DMNNDO was increased from 37% to 45%. The structure of DMNNDO was characterized by IR,^1H NMR,^13 C NMR,and elemental analysis. Also the thermal decomposition of DMNNDO was studied by using DSC and TG-DTG to find that there are primarily two exothermic decomposition processes between 90 and 300 oC. The crystal structure of DMNNDO was studied by X-ray single-crystal diffraction for the first time. The molecular structure exists as a dimeric form due to the presence of nitroso group. The crystal belongs to monoclinic system,space group C2/c with a = 14.515(3),b = 9.955(2),c = 11.897(2) °,β = 98.500(3)°,V = 1.6998(2) nm^3,Z = 8,D_c = 1.486 g×cm^-3,μ = 0.128 mm^-1,F(000) = 800,S = 1.055,R = 0.0358 and wR = 0.0917. In particular,DMNNDO could be easily hydrolyzed in hydrous systems and the hydrolysis mechanism in CDCl_3 was revealed by means of NMR monitoring. 展开更多
关键词 2 2-dimethyl-5-nitro-5-nitroso-1 3-dioxane synthesis crystal structure thermal
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BEHAVIOUR OF α-NITROSO-β-NAPHTHOL IN HEMATITE FLOTATION
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作者 WANG Wenmei YU Yongfu CHEN Quanyuan 《Acta Metallurgica Sinica(English Letters)》 SCIE EI CAS CSCD 1993年第11期4-4,共1页
Based on theoretical calculation of electronegativity of groups of flotation reagent and method of infrared adsorption spectroscopy,the collection and adsorption of α-nitroso-β- naphthol in hematite flotation have b... Based on theoretical calculation of electronegativity of groups of flotation reagent and method of infrared adsorption spectroscopy,the collection and adsorption of α-nitroso-β- naphthol in hematite flotation have been studied.The chemical adsorption seems to be predominant owing to formation of pentacyclic nitrosyl chelate compound by atoms of nitrosyl bond in α-nitroso-β-naphthol together with Fe(Ⅲ)on hematite surface.Mean- while,the nonuniform multilayer physical adsorption is also occurred. 展开更多
关键词 α-nitroso-β-naphthol HEMATITE ELECTRONEGATIVITY chelate property FLOTATION
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Synergistic Extraction of Lanthanides by 1-Nitroso-2-Naphthol and Trioctylphosphine Oxide in Paraffin Wax
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作者 郭效军 高锦章 +4 位作者 范海燕 彭波 王碧 邓启良 康敬万 《Rare Metals》 SCIE EI CAS CSCD 2000年第4期306-311,共6页
The paraffin wax was used as a diluent for 1-nitroso-2-naphthol(HA) and trioctylphosphine oxide(TOPO) in the extraction of lanthanides at 70℃. The composition of the extracted species was given as LnA_3(TOPO)_2 by me... The paraffin wax was used as a diluent for 1-nitroso-2-naphthol(HA) and trioctylphosphine oxide(TOPO) in the extraction of lanthanides at 70℃. The composition of the extracted species was given as LnA_3(TOPO)_2 by means of the slope analysis. The variation of the synergistic extraction equilibrium constant(K_ sex) was investigated at 60~80℃, and the thermodynamic data were calculated. The dependence of separation factors on temperature was also studied. 展开更多
关键词 Synergistic extraction LANTHANIDES 1-nitroso-2-naphthol Trioctylphosphine oxide
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Cobalt Determination by Means of Flow Injection On-line Sorbent Preconcentration-Flame Atomic Absorption Spectrometry with 1-Nitroso-2-naphthol as a Complexing Reagent
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作者 YIN Xue-feng ALI Akbar +3 位作者 XU Guang-ming LING Yun-yang GAO Jian YE Mei-ying 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2001年第3期264-270,共7页
The suitability of 1-nitroso-2-naphthol(NN) as a complexing agent for on-line preconcentration of cobalt eluted on the C_(18) microcolumn by means of the FI-FAAS system was tested. Various parameters affecting the com... The suitability of 1-nitroso-2-naphthol(NN) as a complexing agent for on-line preconcentration of cobalt eluted on the C_(18) microcolumn by means of the FI-FAAS system was tested. Various parameters affecting the complex formation and its elution were optimized. A 2.3×10^(-3) mol/L reagent solution and the aqueous sample solution acidified with 0.1% (volume fraction) nitric acid were on-line mixed (6.4 mL/min) on a reaction coil set at (65±1)℃ and flowed through the microcolumn for 30 s. The pH of the mixed solution was adjusted to 3—4 with HNO_3(1 mol/L) or NaOH(1 mol/L). The adsorbed complexes in the microcolumn were eluted into the nebulizer of FAAS in 10 s with ethanol acidified with 1% HNO_3(3.0 mL/min). A good precision(1.6% for 100μg/L Co(Ⅱ), n=10), a high enrichment factor 17.2, with detection limit (3σ) 3.2μg/L, and sample throughput (90 h^(-1)) were obtained. The method was applied to the certified reference materials(CRMs), NBS-362 and NBS-364, for the determination of cobalt and the results were in good agreement with the certified values. 展开更多
关键词 Cobalt FI on-line preconcentration AAS 1-nitroso-2-naphthol
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Solid-Liquid Extraction of Some Lanthanide Complexes with 1-Nitroso-2-Naphthol
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作者 Jin Zhang GAO Xiao Jun GUO +2 位作者 Bi WANG Qi Liang DENG Hai Yan FAN(Department of Chemistry, Northwest Normal University, Lanzhou 730070) 《Chinese Chemical Letters》 SCIE CAS CSCD 2000年第7期653-654,共2页
The extraction behavior of Sm(III), Eu(III),Er(III) and Yb(III) with 1- nitroso -2-naphthol (HA) in paraffin has been studied. The composition of,extracted complexes has been determined to be LnA(3) by slope analysis ... The extraction behavior of Sm(III), Eu(III),Er(III) and Yb(III) with 1- nitroso -2-naphthol (HA) in paraffin has been studied. The composition of,extracted complexes has been determined to be LnA(3) by slope analysis method. The effect of temperature on extraction system is also investigated and thermodynamic parameters are obtained. 展开更多
关键词 SOLID-LIQUID LANTHANIDE 1-nitroso-2-naphthol
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Inhibitory Effects of S-Nitroso-Glutathione on Sporulation Process of Eimeria tenella Oocysts
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作者 Yu Xing-xing Xing Tao +4 位作者 Zhang Hong-fei Yao Zheng-xing Zhou Guang-sheng Wang Hai-gen Zhu Ai-jun 《Journal of Northeast Agricultural University(English Edition)》 CAS 2017年第1期42-47,共6页
To study the inhibiting effects of S-Nitroso-Glutathione (GSNO) on sporulation process of Eimeria tenella (E. tenella) oocysts by detecting the sporulation rate, GSNO as nitric oxide donor was used to treat E. ten... To study the inhibiting effects of S-Nitroso-Glutathione (GSNO) on sporulation process of Eimeria tenella (E. tenella) oocysts by detecting the sporulation rate, GSNO as nitric oxide donor was used to treat E. tenella oocysts sporulated for different times; Several kinds of antioxidants and oxidants were used to investigate the inhibitory effects of GSNO on sporogony process of E. tenella oocysts. The results showed that GSNO still inhibited the oocysts sporulated 10 h, but had few inhibiting effect on the oocysts sporulated for 14 h; the antioxidants, such as Vitamin C (VC), mannitol and sodium salicylate, could not eliminate the inhibitory effects of GSNO on oocysts; neither did the ferrous sulfate (FeSO4) nor Dithiothreitol (DTT). However, the oxidants, potassium dichromate (K2Cr2OT) and potassium permanganate (KMnO4) could obviously repress the effects of GSNO on oocysts. At present, the inhibitory mechanism of GSNO on unsporulated oocysts was still unclear. 展开更多
关键词 S-nitroso-glutathione Eimeria tenella inhibiting characteristic
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Synthesis and Characterization of Nitrosonaphthol Dyes Based on 1-Naphthol and Their Dyeing Properties on Tanned Leather
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作者 Umar Salami Ameuru Mohammed Kabir Yakubu Kasali Ademola Bello 《Open Journal of Applied Sciences》 2014年第6期354-359,共6页
Nitrosonaphthol dyes and other corresponding analogues were synthesised from 1-Naphthol. The dyes were applied onto chrome and vegetable tanned leather upon characterization. The results indicate that the dye bath exh... Nitrosonaphthol dyes and other corresponding analogues were synthesised from 1-Naphthol. The dyes were applied onto chrome and vegetable tanned leather upon characterization. The results indicate that the dye bath exhaustion was better on chrome tanned leather than on vegetable tanned leather. This may be attributed to the chelating effect of chrome on leather and the higher temperature of dyeing the chrome tanned leather compared with the vegetable tanned leather. The fastness properties of the dyes of washing ranging from (3 - 5), perspiration on acid (4 - 5), alkaline (4 - 5) and light (4 - 7) were impressive on both vegetable and chrome tanned leather respectively. 展开更多
关键词 2-nitroso-1-Naphthol Tanned LEATHER EXHAUSTION FASTNESS
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Emerging progress:photochemical transformation of nitroso compounds
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作者 Ze-Le Chen Qiang-Qiang Li +1 位作者 Armido Studer Jun Xuan 《Science China Chemistry》 2025年第1期118-133,共16页
Nitroso compounds have emerged as highly valuable reaction partners or reagents in organic synthesis due to their rich reactivity.The versatile profile of these compounds allows them to function as electrophiles,nucle... Nitroso compounds have emerged as highly valuable reaction partners or reagents in organic synthesis due to their rich reactivity.The versatile profile of these compounds allows them to function as electrophiles,nucleophiles,diradicals,and radical acceptors in diverse transformations.In recent years,notable progress has been made in harnessing photochemical reactions with nitroso compounds to prepare N,O-containing structures using mild and eco-friendly conditions.Various nitroso compounds like nitrosoarenes,acyloxy nitroso compounds,N-nitrosoamines and nitrites have received significant attention for their ability to introduce NO moieties into complex molecules that are otherwise difficult to access.In this review,we provide an overview of the recent advancements in the visible light-induced conversion of nitroso compounds,with particular emphasis on their role as bifunctional reagents and acceptors of radicals,carbenes and nitrenes. 展开更多
关键词 nitroso compounds PHOTOCHEMISTRY radical reaction carbene transformation nitrosoARENES
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N-亚硝基乙基异丙胺和N-亚硝基二异丙胺致小鼠肝毒性和肠道菌群代谢差异
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作者 文海若 寇小旋 +2 位作者 赵晶 赵婷婷 汪祺 《药物评价研究》 北大核心 2025年第9期2453-2461,共9页
目的从肠道菌群的角度探讨结构相似的N-亚硝基乙基异丙胺(NEIPA)和N-亚硝基二异丙胺(NDIPA)的肝毒性强弱与其代谢途径差异的关联。方法70只C57BL/6J小鼠随机分为7组:对照组(0.5%CMC-Na),NEIPA低、中、高剂量(25、50、100 mg∙kg^(−1))组,... 目的从肠道菌群的角度探讨结构相似的N-亚硝基乙基异丙胺(NEIPA)和N-亚硝基二异丙胺(NDIPA)的肝毒性强弱与其代谢途径差异的关联。方法70只C57BL/6J小鼠随机分为7组:对照组(0.5%CMC-Na),NEIPA低、中、高剂量(25、50、100 mg∙kg^(−1))组,NDIPA低、中、高剂量(25、50、100 mg∙kg^(−1))组,各组连续ig给药7 d,随后设置3周恢复期,并且分别在末次给药和恢复期结束解剖动物和观察指标。实验期间,每天观察动物一般状态,每周测定体质量。末次给药后称肝脏质量、进行血清生化检查和肝组织病理学检查。试验期间收集粪便,并进行16S rRNA基因测序,比较其在肠道菌群结构组成方面的差异。结果与对照组相比,NEIPA组和NDIPA组在首次给药后28 d内均未观察到异常症状或明显体质量下降,且NEIPA组和NDIPA组与对照组在脏器指数上无显著差异;首次给药后7、28 d时,NEIPA高剂量组在丙氨酸氨基转移酶(ALT)水平上显著升高(P<0.01、0.001);给药7 d时,NDIPA高剂量组肌酸激酶(CK)水平显著升高(P<0.05),但在首次给药后28 d时无显著差异。NEIPA中、高剂量组可见肝细胞肥大/核巨大,病变发生率及病变程度随剂量增加而增加;肠道菌群分析结果提示,与对照组相比,在给予NEIPA的小鼠中,Turicibacter、Lactobacillus、Akkermansia和Faecelbaculum的丰度显著增加,Liilactobacilus、f_Lachnospiraceae、Lachnospiraceae_NK4A136_group的丰度降低;在给予NDIPA的小鼠中,f_Muribaculaceae、g_unclassifed_o-Clostridia_UCG-014、Lactobacillus和Akkermansia的丰度增加,Lachnospiraceae_NK4A136和liilactobacilus的丰度降低。结论NEIPA仅比NDIPA多一个α-氢原子,但肝毒性存在一定差异,NEIPA增加了与胆汁酸代谢相关的Turicibacter的丰度,NDIPA增加了有促炎作用的o-Clostridia_UCG-014的丰度。NEIPA和NDIPA肝毒性风险的差异可能归因于它们不同的代谢途径,相关代谢途径及机制有待深入研究。 展开更多
关键词 N-亚硝基杂质 N-亚硝基乙基异丙胺(NEIPA) N-亚硝基二异丙胺(NDIPA) C57BL/6J小鼠 肠道菌群代谢 遗传毒性 肝毒性
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胃萎方通过抑制核因子-κB/信号转导及转录激活蛋白3信号通路逆转N-甲基-N’-硝基-N-亚硝基胍诱导的大鼠胃癌前病变
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作者 陈丽凤 陈默 +4 位作者 吴昦辰 郑启忠 黄墩煌 张冬英 陈一斌 《中医临床研究》 2025年第6期29-34,共6页
目的:研究胃萎方对信号转导及转录激活蛋白3(Signal Transducer and Activator of Transcription 3,STAT3)/核因子-κB(Nuclear Factor-κB,NF-κB)信号通路的调控作用,探讨胃萎方对胃癌前病变(Precancerous Lesion of Gastric Cancer,P... 目的:研究胃萎方对信号转导及转录激活蛋白3(Signal Transducer and Activator of Transcription 3,STAT3)/核因子-κB(Nuclear Factor-κB,NF-κB)信号通路的调控作用,探讨胃萎方对胃癌前病变(Precancerous Lesion of Gastric Cancer,PLGC)的疗效及作用机制。方法:从70只雄性Wistar大鼠中随机选择20只作为空白组,其余50只为造模组。采用N-甲基-N’-硝基-N-亚硝基胍(MNNG)诱导GPL大鼠实验模型。14周后,对随机选择的造模组大鼠10只进行胃组织学分析,确认造模成功,造模组剩余40只大鼠随机分为模型组、胃萎方治疗组各20只。使用胃萎方干预后,观察大鼠体质量增长、胃黏膜组织结构变化,以及血清胃蛋白酶原(Pepsinogen,PG)Ⅰ,PGⅡ和胃泌素的浓度,并检测NF-κB p65和STAT3的基因及蛋白表达。结果:与空白组比较,模型组大鼠体质量增长缓慢,胃黏膜组织细胞异型增生明显,血清PGⅠ、胃泌素水平和PGⅠ/PGⅡ比值显著降低,胃黏膜NF-κB/STAT3信号通路被激活;与模型组比较,胃萎方治疗组大鼠整体情况改善,胃黏膜组织结构重塑、萎缩性胃黏膜和非典型腺上皮减少,PGⅠ/PGⅡ比值和胃泌素水平增加(P<0.01),NF-κB p65和STAT3的mRNA及蛋白的表达受到一定程度的抑制(P<0.05)。结论:胃萎方能够通过抑制NF-κB/STAT3信号通路逆转MNNG诱导的大鼠GPL,为胃萎方的临床应用提供了基础证据。 展开更多
关键词 胃萎方 胃癌前病变 核因子-ΚB 信号转导及转录激活蛋白3 N-甲基-N’-硝基-N-亚硝基胍
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盐酸曲美他嗪中潜在基因毒性杂质N-亚硝基曲美他嗪的HPLC-MS/MS测定研究
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作者 钞瑞瑞 陈恪然 +5 位作者 刘佳莹 李佳炜 刘依铭 陆宇婷 宋敏 杭太俊 《药学与临床研究》 2025年第3期227-230,共4页
目的:建立盐酸曲美他嗪中潜在基因毒性杂质N-亚硝基曲美他嗪的高效液相色谱-串联质谱检测(HPLC-MS/MS)方法并进行检查研究。方法:用Shimadzu VP-ODS-C_(18)(4.6 mm×250 mm,5μm)色谱柱,0.1%甲酸水溶液与0.1%甲酸甲醇溶液为流动相... 目的:建立盐酸曲美他嗪中潜在基因毒性杂质N-亚硝基曲美他嗪的高效液相色谱-串联质谱检测(HPLC-MS/MS)方法并进行检查研究。方法:用Shimadzu VP-ODS-C_(18)(4.6 mm×250 mm,5μm)色谱柱,0.1%甲酸水溶液与0.1%甲酸甲醇溶液为流动相进行梯度洗脱分离,同位素内标法ESI正离子化MRM检测盐酸曲美他嗪中的N-亚硝基曲美他嗪。结果:N-亚硝基曲美他嗪在0.5~100 ng·mL^(-1)浓度范围内有良好的线性关系;检测限和定量限分别达0.2 ng·mL^(-1)和0.5 ng·mL^(-1);回收率在94.58%~101.4%之间。结论:建立的N-亚硝基曲美他嗪HPLCMS/MS方法专属灵敏准确,可以用于盐酸曲美他嗪中潜在基因毒性杂质的限度研究。 展开更多
关键词 曲美他嗪 N-亚硝基曲美他嗪 基因毒性杂质 高效液相色谱-串联质谱检测
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QUANTITATIVE PATTERN RECOGNITION FOR STRUCTURE-CARCINOGENIC ACTIVITY RELATIONSHIP OF N-NITROSO COMPOUNDS BASED UPON DI-REGION THEORY 被引量:1
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作者 戴乾圜 钟儒刚 《Science China Chemistry》 SCIE EI CAS 1989年第7期776-790,共15页
In this paper, it is evidenced by the quantitative structu re-carcinogenic activity relation-ship (QSCAR) and the pattern recognition treatment of N-nitroso compounds (NNC) that thekey step of carcinogenesis induced b... In this paper, it is evidenced by the quantitative structu re-carcinogenic activity relation-ship (QSCAR) and the pattern recognition treatment of N-nitroso compounds (NNC) that thekey step of carcinogenesis induced by NNC is the cross-linking on the complementary basepair of DNA, through the bifunctional alkylation between α-carbon and another carbonwithin the same chain. The alkylation by the α-carbon atom is through the diazonium salt,but that by the atom other than the α-position is through the active ester formed from thehydroxylated metabolite of the chain. Therefore, the alkylation by the β-position of NNC,or by its γ-position under suitable conditions, of which the distances from the α-positionboth approach 2. 80-3. 00 A, would be the most favourable positions along with the α-posi-tion for the cross-linking to occur between the complementary base pairs of DNA, whichwill yield the carcinogenic activity of NNC. The above conception of bifunctional alkyla-tion can reduce the QSCAR of NNC to a reasonable structure-chemical reactivity relationshipunder the complex biological conditions, and is the successful extension of the Di-regiontheory to the carcinogenesis mechanism of the important NNC series. In the light of theabove viewpoint, for 153 NNCs including the nitrosamines and nitrosamides which havebeen tested reliably with animals, the correct discrimination ratio by quantitative patternrecognition according to carcinogenic activity indexes divided into 5 degrees comes up to ashigh as 97%. 展开更多
关键词 N-nitroso COMPOUNDS Di-region theory pattern recognition chemical CARCINOGENESIS structure-carcinogenic activity relationship
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N-亚硝基布美他尼体外致突变性风险评价
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作者 蒋晨晨 靳龙龙 +4 位作者 寇小旋 宋捷 石皓琨 黄勤 文海若 《中国药物警戒》 2025年第10期1114-1119,1131,共7页
目的评估N-亚硝基布美他尼的体外致突变性风险,为其安全性评价提供依据。方法采用Derek Nexus和Sarah Nexus软件进行构效分析,预测其致突变性及警示结构;参照欧洲药品管理局(European Medicines Agency,EMA)指南,开展增强细菌回复突变试... 目的评估N-亚硝基布美他尼的体外致突变性风险,为其安全性评价提供依据。方法采用Derek Nexus和Sarah Nexus软件进行构效分析,预测其致突变性及警示结构;参照欧洲药品管理局(European Medicines Agency,EMA)指南,开展增强细菌回复突变试验(使用鼠伤寒沙门氏菌TA98、TA100、TA1535、TA1537和大肠杆菌WP2 uvrA(pKM101)菌株,在无代谢活化、30%大鼠S9和30%仓鼠S9代谢活化及预培养30 min条件下进行);同时进行小鼠淋巴瘤细胞tk基因突变试验(Mouse Lymphoma Assay,MLA),检测其在不同处理条件下的细胞毒性和突变频率。结果构效预测显示,Derek Nexus因N-亚硝基结构预测其存在细菌突变风险(评级“貌似可信”),Sarah Nexus评级为“模棱两可”。增强细菌回复突变试验中,每皿125~5000μg剂量下,各菌株回复突变菌落数未明显增加;MLA试验中,312.5~2500μg·mL^(-1)浓度范围内,细胞相对总生长率(Relative Total Growth,RTG)未见明显毒性,突变频率与阴性对照组相比无明显差异,结果均为阴性。结论N-亚硝基布美他尼在体外试验条件下未显示致突变性风险,为其风险评估提供参考。 展开更多
关键词 N-亚硝基布美他尼 致突变性 细菌回复突变试验 小鼠淋巴瘤细胞试验 构效分析 药物安全性评价
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5种β受体拮抗剂类药物中的N-亚硝基类杂质的含量研究
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作者 田珩 杨仪雪 +2 位作者 戴聪 刘亚雄 严全鸿 《中国药房》 CAS 北大核心 2024年第8期936-941,共6页
目的测定普萘洛尔、美托洛尔、阿替洛尔、艾司洛尔、比索洛尔原料药/制剂中N-亚硝基类杂质含量,明确其含量的关注阈值。方法采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱技术。以ACE Excel 3 C18-AR为色谱柱,以含0.01 mol/L乙酸铵... 目的测定普萘洛尔、美托洛尔、阿替洛尔、艾司洛尔、比索洛尔原料药/制剂中N-亚硝基类杂质含量,明确其含量的关注阈值。方法采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱技术。以ACE Excel 3 C18-AR为色谱柱,以含0.01 mol/L乙酸铵的0.2%甲酸溶液-甲醇为流动相进行梯度洗脱,流速为0.60 mL/min,柱温为40℃,进样量为5μL;以可加热的电喷雾离子源为离子源,以全扫描-选择离子监测模式进行正离子扫描。采用该法对10家企业生产的15批β受体拮抗剂类药物原料药/制剂中N-亚硝基类杂质含量进行测定,并采用Discovery Studio软件对待测杂质进行毒性预测和关注阈值估算。结果5种β受体拮抗剂类药物中,N-亚硝基普萘洛尔、N-亚硝基美托洛尔、N-亚硝基阿替洛尔、N-亚硝基艾司洛尔、N-亚硝基比索洛尔检测质量浓度的线性范围分别为1.01~503.38、1.02~508.38、0.97~483.63、1.11~554.27、1.05~523.92 ng/mL(r>0.999),定量限分别为1.04、0.25、0.05、0.55、1.05 ng/mL,检测限分别为0.52、0.08、0.02、0.17、0.52 ng/mL,精密度、重复性、加样回收率、稳定性、耐用性试验的RSD均小于7.5%(n=6或n=5)。15批样品中,除1批样品外,其余批次均检出了N-亚硝基普萘洛尔(1.07~8.91 ng/mg)、N-亚硝基美托洛尔(1.43~3.37 ng/mg)、N-亚硝基阿替洛尔(1.33 ng/mg)、N-亚硝基艾司洛尔(0.19 ng/mg)、N-亚硝基比索洛尔(1.27 ng/mg)。经预测,上述5种杂质有不同程度的生育毒性、致突变性、致癌性,关注阈值分别为1.0、0.4、4.3、0.2、46.7 ng/mg。结论所建方法简单快捷、灵敏度高、专属性强,估算的关注阈值明确,可用于多种β受体拮抗剂类药物中N-亚硝基类杂质的含量控制。 展开更多
关键词 β受体拮抗剂类药物 N-亚硝基类杂质 超高效液相色谱-四极杆/静电场轨道阱高分辨质谱技术 基因毒性 关注阈值
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N-亚硝基二甲胺和N-亚硝基二乙胺的小鼠重复给药毒性及遗传毒性研究 被引量:3
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作者 叶倩 汪祺 +3 位作者 林志 杨艳伟 耿兴超 文海若 《药物评价研究》 CAS 北大核心 2024年第1期57-67,共11页
目的 连续7 d重复给予C57BL/6J小鼠N-亚硝基二甲胺(NDMA)和N-亚硝基二乙胺(NDEA),观察至首次给药后28 d,评价两者主要毒性靶器官及遗传毒性风险。方法 分设溶媒对照组(0.5%羧甲基纤维素钠),受试物组(分别给予0.75、1.50、3.00 mg·k... 目的 连续7 d重复给予C57BL/6J小鼠N-亚硝基二甲胺(NDMA)和N-亚硝基二乙胺(NDEA),观察至首次给药后28 d,评价两者主要毒性靶器官及遗传毒性风险。方法 分设溶媒对照组(0.5%羧甲基纤维素钠),受试物组(分别给予0.75、1.50、3.00 mg·kg^(-1)NDMA或3.25、7.50、15.00 mg·kg^(-1)NDEA)和阳性对照组(200 mg·kg^(-1)甲磺酸乙酯、40 mg·kg^(-1)N-乙基-N-亚硝基脲)。溶媒对照组和受试物组连续7 d每天ig给药1次,阳性对照组连续3 d每天ig给药1次。末次给药后开展小鼠肝、肾和外周血彗星试验,计算每只动物的肝、肾和血细胞尾DNA百分含量(%Tail DNA)和尾距(tail moment)平均值。观察结束后(D28)开展小鼠磷脂酰肌醇聚糖A类(Pig-a)基因突变试验,计算网织红细胞(RETCD24-)和总红细胞(RBCCD24-)的突变率。并在末次给药和恢复期结束后,试剂盒法检测小鼠肝、肾和肺的8-羟基脱氧鸟苷(8-OHdG)水平、实时荧光定量PCR(qRT-PCR)法检测DNA损伤基因(ATM、gH2AX、Nbn、Prkdc、Trp)和肝药酶基因(CYP2E1、CYP2A6)。结果 NDMA剂量为3 mg·kg^(-1)时,动物全部死亡,自连续给药4 d后,NDEA 15 mg·kg^(-1)组小鼠体质量与溶媒对照组相比显著性降低(P<0.001);且NDMA和NDEA组与溶媒对照组在脏器系数、血液生化指标、组织病理学等方面存在显著差异(P<0.05、0.01、0.001),提示NDMA和NDEA对肝脏和肾脏存在一定毒性;NDMA和NDEA组小鼠肝、肾彗星试验结果均为阳性,Pig-a基因突变试验中NDEA高剂量组RETCD24-结果为阳性;与溶媒对照组比较,NDMA和NDEA组小鼠肝、肾和肺中8-OHdG含量显著升高(P<0.05、0.001),DNA损伤和肝药酶基因表达也存在显著差异(P<0.05、0.001)。结论 NDMA分别在1.5 mg·kg^(-1)剂量条件下产生肝脏毒性,0.75、1.50 mg·kg^(-1)剂量条件下使小鼠肝、肾细胞产生致突变性和肝、肾DNA损伤;NDEA可在15 mg·kg^(-1)剂量条件下产生肝脏毒性,并导致肝、肾细胞产生致突变性和DNA损伤;8-OHdG和DNA损伤基因等指标检测结果与NDMA和NDEA遗传毒性结果具有一定关联性。 展开更多
关键词 N-亚硝基杂质 N-亚硝基二甲胺 N-亚硝基二乙胺 重复给药毒性试验 C57BL/6J小鼠 彗星试验 Pig-a基因突变试验 遗传毒性
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羧基亚硝基氟橡胶在液相四氧化二氮中的老化行为
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作者 李少范 苏允兰 +2 位作者 张欢 许文 赵莹 《宇航材料工艺》 CSCD 北大核心 2024年第6期105-112,共8页
采用多种分析测试方法研究了羧基亚硝基氟橡胶在液相四氧化二氮(N_(2)O_(4))介质中的老化行为。差式扫描量热分析、热重分析、溶剂溶胀方法和扫描电子显微镜结果表明,随着老化天数的增加,样品的玻璃化转变温度(T_(g))未发生明显变化,但... 采用多种分析测试方法研究了羧基亚硝基氟橡胶在液相四氧化二氮(N_(2)O_(4))介质中的老化行为。差式扫描量热分析、热重分析、溶剂溶胀方法和扫描电子显微镜结果表明,随着老化天数的增加,样品的玻璃化转变温度(T_(g))未发生明显变化,但是热稳定性有所下降,溶胀度增加,同时样品表面逐渐出现微裂纹;表明样品在液相介质中逐渐发生老化。X-射线光电子能谱结果表明,与未老化样品相比,老化样品表面各元素含量并未发生明显变化,但部分交联点被破坏。热重-红外-气相色谱/质谱联用系统结果表明老化过程中,白炭黑填料的表面改性剂在N_(2)O_(4)介质作用下发生氧化,从而降低了样品的热稳定性。 展开更多
关键词 羧基亚硝基氟橡胶 热稳定性 表面形貌 老化行为
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HPLC-MS/MS法测定盐酸拉贝洛尔中潜在基因毒性杂质 被引量:4
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作者 韩佳芮 徐艳梅 +1 位作者 郝丽娟 高燕霞 《河北科技大学学报》 CAS 北大核心 2024年第3期277-282,共6页
为了更好地控制盐酸拉贝洛尔中潜在的基因毒性杂质,保证用药安全,建立了高效液相色谱-质谱(HPLC-MS/MS)法检测盐酸拉贝洛尔中潜在遗传毒性杂质N-亚硝基拉贝洛尔。液相色谱条件:以Waters ACQUITY UPLC CSH C_(18)(150 mm×3.0 mm,1.7... 为了更好地控制盐酸拉贝洛尔中潜在的基因毒性杂质,保证用药安全,建立了高效液相色谱-质谱(HPLC-MS/MS)法检测盐酸拉贝洛尔中潜在遗传毒性杂质N-亚硝基拉贝洛尔。液相色谱条件:以Waters ACQUITY UPLC CSH C_(18)(150 mm×3.0 mm,1.7μm)为色谱柱,流动相A为0.01 mol/L甲酸铵-0.1%甲酸水溶液,流动相B为乙腈溶液,梯度洗脱,流速为0.5 mL/min,柱温为50℃,进样体积为10μL。以电喷雾电离源为离子源,负离子模式,采用多反应监测,建立质谱条件,对盐酸拉贝洛尔中N-亚硝基拉贝洛尔进行定量检测。结果表明:N-亚硝基拉贝洛尔质量浓度在1.01~100.60 ng/mL范围内有良好的线性关系;低、中、高3个浓度的加样回收率(n=3)为96.84%~99.53%;检测限和定量限分别为0.01 ng/mL和0.03 ng/mL;6批盐酸拉贝洛尔样品中N-亚硝基拉贝洛尔的含量为0.37~0.79 ng/mL。所提出的方法灵敏度高、专属性强,可用于测定盐酸拉贝洛尔中的N-亚硝基拉贝洛尔,为盐酸拉贝洛尔的质量控制提供参考。 展开更多
关键词 化学分析 盐酸拉贝洛尔 HPLC-MS/MS 基因毒性杂质 N-亚硝基拉贝洛尔
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1,3-苯二氮衍生物的合成
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作者 刘莹 侯梦利 白娟 《合成化学》 CAS 2024年第7期610-621,共12页
苯二氮类化合物具有强大的药理作用,是药物化学和有机合成工作者研究的热点。近几年研究发现:1,3-苯二氮类衍生物同样具有生物活性,也可作为临床药物。因此本课题利用7-endo亚硝基-烯反应构建1,3-苯二氮衍生物,从市售的含不同取代基的... 苯二氮类化合物具有强大的药理作用,是药物化学和有机合成工作者研究的热点。近几年研究发现:1,3-苯二氮类衍生物同样具有生物活性,也可作为临床药物。因此本课题利用7-endo亚硝基-烯反应构建1,3-苯二氮衍生物,从市售的含不同取代基的邻氨基苯乙酮系列化合物出发,将其转化为羟肟酸后,在CuCl_(2)/H_(2)O_(2)体系下,发生7-endo亚硝基-烯反应,生成1,3-苯二氮类衍生物。 展开更多
关键词 亚硝基-烯反应 邻氨基苯乙酮 羟肟酸 1 3-苯二氮 有机合成
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