2-(5-十四碳烯基)环丁酮 | 142784-27-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 2-(5-十四碳烯基)环丁酮
• 英文名称: N-(acetyloxy)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
• 英文别名: 2-(acetyloxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine；N-acetoxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine；2-(acetoxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine；N-Acetoxy-phip；[(1-methyl-6-phenylimidazo[4,5-b]pyridin-2-yl)amino] acetate
• CAS: 142784-27-8
• 化学式: C₁₅H₁₄N₄O₂
• 分子量: 282.302
• InChiKey: OVPSYMLYTZOTQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  69
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(5-十四碳烯基)环丁酮 生成 5-羟基-异构酶P
  参考文献：
  名称：

  在人血浆和肝细胞中由2-氨基-1-甲基苯基咪唑并[4,5- b ]吡啶的N-氧化代谢产物形成的人血清白蛋白加合物的质谱表征

  摘要：

  2-氨基-1-甲基-6-苯基咪唑并[4,5- b ]吡啶（PhIP）是在熟肉中形成的致癌性杂环芳香胺，被代谢活化为亲电子中间体，该中间体与DNA和蛋白质形成共价加合物。我们先前确定了白蛋白与遗传毒性代谢物2-羟基氨基-1-甲基-6-苯基咪唑并[4,5- b ]吡啶（HONH-PhIP）反应后，在人血清白蛋白的Cys 34残基上形成的PhIP加合物。从胰蛋白酶/胰凝乳蛋白酶消化物中回收的主要加成肽被鉴定为缺失的裂解肽LQQC * [SO 2 PhIP]PFEDHVK，[半胱氨酸-S-基-PhIP] -S-二氧化物连接的加合物。在这项研究中，我们已经表征了N-磺氧基-2-氨基-1-甲基-6-苯基咪唑并[4,5- b ]吡啶（N-磺氧基-PhIP）的白蛋白加合产物，这被认为是主要的PhIP的遗传毒性代谢物在体内形成。靶向和依赖数据的扫描方法表明，N-磺氧基-PhIP与人血浆中白蛋白的Cys 34加成后形成LQQC

  DOI：

  10.1021/acs.chemrestox.5b00075
• 作为产物：
  描述：

  乙酸酐 、 N-(1-甲基-6-苯基咪唑并[4,5-b]吡啶-2-基)羟胺 以 甲醇 、 溶剂黄146 为溶剂， 反应 0.17h， 以75%的产率得到2-(5-十四碳烯基)环丁酮
  参考文献：
  名称：

  Heterogeneous DNA Adduct Formation in Vitro by the Acetylated Food Mutagen 2-(Acetoxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine: A Fluorescence Spectroscopic Study

  摘要：

  The food mutagen 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) forms adducts to DNA guanine bases at the C-8 position. No other DNA adduction site has been verified for PhIP, nor has any experimental data been collected on the conformation of the PhIP-DNA covalent complex. To determine if multiple PhIP-DNA adduct species exist, or if PhIP-DNA adducts assume multiple conformations, 2-(acetoxyamino)-1-methyl-6-phenylimidazo [4,5-b]-pyridine (N-acetoxy-PhIP) was reacted with calf thymus DNA, followed by an evaluation of the resulting adduct complexes by fluorescence spectroscopy. Approximately 20% of the N-acetoxy-PhIP formed covalent complexes with DNA. Two major and several minor spots were observed by P-32-postlabeling, suggesting a minimum of two major adduct species. UV/vis spectra of the PhIP-modified DNA also showed heterogeneous formation of PhIP-DNA adducts. Fluorescence excitation and emission spectroscopy with or without fluorescence quenching (silver ion and acrylamide) was used to evaluate the number of adducts formed, and the low-resolution conformation of each adduct. Four adduct fluorophores were observed and assigned the nomenclature PAi, where ''PA'' denotes PhIP Adduct and i = 1-4 in order of fluorescence emission band energies, with 1 the highest and 4 the lowest energy, respectively. Excitation maxima for the adduct fluorophores ranged from 340 to 370 nm, and emission maxima ranged from 390 to 420 nm. The fluorescence from adduct PA1 was quenched by silver but not acrylamide, suggesting a helix-internal configuration. Adduct PA2 fluorescence was strongly enhanced upon silver binding but was not affected by acrylamide, also indicating that this adduct was internal. The fluorescence from adducts PA3 and PA4 was quenched by acrylamide but not silver; thus PA2 and PA3 were tentatively assigned as solvent-accessible. These data are the first suggesting heterogeneous formation of PhIP adducts to intact DNA, but we cannot as yet determine how many chemical species of adduct are formed or if a given species exists in multiple conformations.

  DOI：

  10.1021/tx00047a005

文献信息

• Identification of Carcinogen DNA Adducts in Human Saliva by Linear Quadrupole Ion Trap/Multistage Tandem Mass Spectrometry
  作者：Erin E. Bessette、Simon D. Spivack、Angela K. Goodenough、Tao Wang、Shailesh Pinto、Fred F. Kadlubar、Robert J. Turesky

  DOI：10.1021/tx100098f

  日期：2010.7.19

  DNA adducts of carcinogens derived from tobacco smoke and cooked meat were identified by liquid chromatography−electrospray ionization/multistage tandem mass spectrometry (LC-ESI/MS/MSn) in saliva samples from 37 human volunteers on unrestricted diets. The N-(deoxyguanosin-8-yl) (dG-C8) adducts of the heterocyclic aromatic amines 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-9H-pyrido[2

  通过液相色谱-电喷雾电离/多级串联质谱 (LC-ESI/MS/MS n ) 在来自 37 名无限制饮食的人类志愿者的唾液样本中鉴定了源自烟草烟雾和熟肉的致癌物的 DNA 加合物。杂环芳香胺 2-amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine (PhIP), 2-amino-9 H的N -(deoxyguanosin-8-yl) (dG-C8) 加合物-吡啶并[2,3- b ]吲哚(AαC)、2-氨基-3,8-二甲基咪唑[4,5- f ]喹喔啉(MeIQx)和芳香胺4-氨基联苯(4-ABP)是通过 LC-ESI/MS/MS n 进行表征和定量，在 MS 3处采用连续反应监测使用线性四极杆离子阱 (LIT) 质谱仪 (MS) 的扫描阶段模式。PhIP 的 DNA 加合物最常被发现：dG-C8-PhIP 在 29 名曾经吸烟者中有 13 名的唾液样本和
• Screening for DNA Adducts by Data-Dependent Constant Neutral Loss-Triple Stage Mass Spectrometry with a Linear Quadrupole Ion Trap Mass Spectrometer
  作者：Erin E. Bessette、Angela K. Goodenough、Sophie Langouët、Isil Yasa、Ivan D. Kozekov、Simon D. Spivack、Robert J. Turesky

  DOI：10.1021/ac802096p

  日期：2009.1.15

  A two-dimensional linear quadrupole ion trap mass spectrometer (LIT/MS) was employed to simultaneously screen for DNA adducts of environmental, dietary, and endogenous genotoxicants, by data-dependent constant neutral loss scanning followed by triple-stage mass spectrometry (CNL-MS3). The loss of the deoxyribose (dR) from the protonated DNA adducts ([M + H − 116]+) in the MS/MS scan mode triggered the acquisition of MS3 product ion spectra of the aglycone adducts [BH2]+. Five DNA adducts of the tobacco carcinogen 4-aminobiphenyl (4-ABP) were detected in human hepatocytes treated with 4-ABP, and three DNA adducts of the cooked-meat carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) were identified in the livers of rats exposed to MeIQx, by the CNL-MS3 scan mode. Buccal cell DNA from tobacco smokers was screened for DNA adducts of various classes of carcinogens in tobacco smoke including 4-ABP, 2-amino-9H-pyrido[2,3-b]indole (AαC), and benzo[a]pyrene (BaP); the cooked-meat carcinogens MeIQx, AαC, and 2-amino-1-methyl-6-phenylmidazo[4,5-b]pyridine (PhIP); and the lipid peroxidation products acrolein (AC) and trans-4-hydroxynonenal (HNE). The CNL-MS3 scanning technique can be used to simultaneously screen for multiple DNA adducts derived from different classes of carcinogens, at levels of adduct modification approaching 1 adduct per 108 unmodified DNA bases, when 10 μg of DNA is employed for the assay.

  利用二维线性四极杆离子阱质谱仪（LIT/MS），通过数据依赖性恒定中性损失扫描和三级质谱（CNL-MS3），同时筛选环境、饮食和内源性基因毒性物质的 DNA 加合物。在 MS/MS 扫描模式下，质子化 DNA 加合物（[M + H - 116]+）中脱氧核糖（dR）的损失触发了琼脂糖核苷酸加合物 [BH2]+ 的 MS3 产物离子谱的获取。通过 CNL-MS3 扫描模式，在经 4-ABP 处理的人类肝细胞中检测到五种烟草致癌物 4- 氨基联苯（4-ABP）的 DNA 加合物，在暴露于 MeIQx 的大鼠肝脏中检测到三种熟肉致癌物 2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉（MeIQx）的 DNA 加合物。对烟草烟雾中各类致癌物质（包括 4-ABP、2-氨基-9H-吡啶并[2,3-b]吲哚（AαC）和苯并[a]芘（BaP））的 DNA 加合物进行了筛查；熟肉致癌物 MeIQx、AαC 和 2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶 (PhIP)；以及脂质过氧化产物丙烯醛 (AC) 和反式-4-羟基壬烯醛 (HNE)。CNL-MS3 扫描技术可用于同时筛查来自不同类别致癌物的多种 DNA 加合物，当使用 10 μg DNA 进行检测时，加合物修饰水平接近每 108 个未修饰 DNA 碱基 1 个加合物。
• Carcinogen-DNA adducts in human breast epithelial cells
  作者：K. Gorlewska-Roberts、B. Green、M. Fares、C.B. Ambrosone、F.F. Kadlubar

  DOI：10.1002/em.10060

  日期：——

  Diet and environmental exposures are often regarded as significant etiologic factors in human breast cancer. Chemicals that may be involved in these exposures include heterocyclic amines, aromatic amines, and polycyclic aromatic hydrocarbons, which also serve as strong mammary carcinogens in different animal models. In this study, we chose to quantify the major DNA adducts derived from one member of

  饮食和环境暴露通常被认为是人类乳腺癌的重要病因。这些暴露中可能涉及的化学物质包括杂环胺，芳香胺和多环芳香烃，它们在不同的动物模型中也可作为强致癌物。在这项研究中，我们选择量化源自每种致癌物类别中的一种的主要DNA加合物，即2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP），从人乳中脱落的导管上皮细胞中分离出的DNA中分别存在4-氨基联苯（ABP）和苯并[a] py（B [a] P）。牛奶是从健康，禁烟的母亲那里收集的。将分离的DNA消化成3'核苷酸，并进行（32）P-后标记。使用Oasis Sep-Paks进行加合物富集，并使用放射线检测通过HPLC进行分析。对于分析至关重要的是合成PhIP和ABP的C8-dG加成物的双（磷酸盐）标准品和B [a] P的N（2）-dG加成物，它们作为紫外线标记添加到每个反应中。在分析的64个样品中，发现了31个样品中的加合物。30个样品包含可检测水平的PhIP加合物，平均值为4
• Characterization of a peptide adduct formed by N-acetoxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a reactive intermediate of the food carcinogen PhIP
  作者：C.L Chepanoske、K Brown、K.W Turteltaub、K.H Dingley

  DOI：10.1016/j.fct.2003.11.012

  日期：2004.8

  2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a member of a class of compounds known as the heterocyclic amines (HCAs) that are formed in meat during cooking. It is a multi-organ carcinogen in rodents forms adducts and with DNA and protein. Although protein adducts are not thought to be involved in cancer development, they may be useful as internal dosimeters of PhIP exposure and bioactivation

  2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）是一类在烹饪过程中在肉中形成的称为杂环胺（HCA）的成员。它是一种多器官致癌物，以啮齿动物形式形成加合物，并带有DNA和蛋白质。尽管蛋白质加合物不被认为与癌症发展有关，但它们可作为PhIP暴露和生物激活的内部剂量计。为了表征在人类中形成的加合物以及开发定量加合物水平的测定方法，我们已经表征了由假定的遗传毒性代谢物N-乙酰氧基-PhIP形成的肽加合物。具有内部序列Leu-Gln-Lys-Cys-Pro-Tyr的模型肽，该序列与人血清白蛋白中HCA的潜在靶序列同源，将其与N-乙酰氧基-PhIP反应并鉴定加合物，并通过LC-ESI-MS / MS进一步表征。N-乙酰氧基-PhIP通过半胱氨酸和PhIP的环外氨基与肽共价结合。需要进一步的工作来确定这种加合物是否形成并在暴露于PhIP后在人体中在体内稳定。
• Liver cell clones for artifical liver and extracorporeal liver assist device
  申请人：JMS Co., Ltd.

  公开号：EP1063289A1

  公开（公告）日：2000-12-27

  Disclosed is a blood perfusion device or apparatus that is used for bioartificial liver support. Human hepatocyte lines established from normal regenerating liver tissue and modulated in toxin-challenging conditions are provided. These functional hepatocytes exhibit extraordinarily enhanced detoxification functions, which are characterised by the elevated glutathione content and glutathione S-transferase activity. A bioreactor is constructed with the functional hepatocytes for bioartificial liver support system, which includes perfusion inlets and perfusion outlets, a containment vessel, a centrifugal pump and macroporous microcarriers where the functional hepatocytes are grown.

  所公开的是一种用于生物人工肝支持的血液灌流装置或设备。提供了从正常再生肝组织中建立并在毒素挑战条件下调节的人类肝细胞系。这些功能性肝细胞的解毒功能异常增强，其特点是谷胱甘肽含量和谷胱甘肽 S 转移酶活性升高。该系统包括灌注入口和灌注出口、密闭容器、离心泵和生长功能肝细胞的大孔微载体。