2-氨基-3,4-二甲基-3H-咪唑并喹啉 | 77094-11-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 2-氨基-3,4-二甲基-3H-咪唑并喹啉
• 中文别名: 2-氨基-3,4-二甲基-3H-咪唑并[4,5-f]喹啉
• 英文名称: 2-amino-3,4-dimethylimidazo[4,5-f]quinoline
• 英文别名: 2-amino-3,4-dimethylimidazo<4,5-f>quinoline；2-amino-3,4-dimethyl-3H-imidazo[4,5-f]quinoline；2-Amino-3,4-dimethylimidazo(4,5-f)quinoline；3,4-dimethylimidazo[4,5-f]quinolin-2-amine
• CAS: 77094-11-2
• 化学式: C₁₂H₁₂N₄
• mdl: MFCD00468067
• 分子量: 212.254
• InChiKey: GMGWMIJIGUYNAY-UHFFFAOYSA-N

物化性质

• 熔点：
  291-293
• 沸点：
  342.09°C (rough estimate)
• 密度：
  1.2046 (rough estimate)
• 溶解度：
  少许溶于甲醇
• 物理描述：
  2-amino-3,4-dimethylimidazo(4,5-f)quinoline appears as pale orange crystalline solid or light yellow powder. (NTP, 1992)
• 颜色/状态：
  Crystals
• 蒸汽压力：
  9.9X10-10 mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
• 解离常数：
  pKa1 = 3.72 (secondary amine); pKa2 = 7.31 (secondary amine)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  56.7
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

人类细胞色素P450 1A2在外源化学物质代谢中催化重要的反应，包括致癌芳香胺的N-羟基化。2001年，Chevalier等人报道了人类群体中四个新的P450 1A2序列变异...这些变异在大肠杆菌中得到了表达，并对蛋白质表达（全酶的光谱测量和免疫印迹）以及IQ（2-氨基-3-甲基咪唑[4,5-f]喹啉）和MeIQ（2-氨基-2,4-二甲基咪唑[4,5-f]喹啉）在lacZ回复突变试验中的生物活化进行了测量。对五种杂环胺底物的N-羟基化以及非那西汀的O-脱乙基化进行了酶动力学分析。R431W替换产生了最显著的影响：没有检测到全酶。这个残基位于“螺旋”肽区域，早期的定点突变研究表明它对维持蛋白质的三级结构至关重要。其他三个变异与野生型酶相比具有细微不同的催化活性。

Human cytochrome P450 1A2 catalyzes important reactions in xenobiotic metabolism, including the N-hydroxylation of carcinogenic aromatic amines. In 2001, Chevalier et al. reported four new P450 1A2 sequence variants in the human population ...These variants /have been expressed/ in Escherichia coli and protein expression (optical spectroscopy of holoenzyme and immunoblotting) and bioactivation of IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and MeIQ (2-amino-2,4-dimethylimidazo[4,5-f]quinoline) in the lacZ reversion mutagenicity test /were measured/. Enzyme kinetic analyses were performed for N-hydroxylation of five heterocyclic amine substrates and for O-deethylation of phenacetin. The most drastic effect was that of the R431W substitution: no holoenzyme was detectable. This residue is located in the "meander" peptide region and earlier site-directed mutagenesis studies demonstrated that it is critical for maintenance of protein tertiary structure. The other three variants had subtly different catalytic activities compared to the wild-type enzyme.

来源:Hazardous Substances Data Bank (HSDB)

代谢

MeIQ在多种途径下进行代谢，包括N-羟基化、芳香族羟基化以及乙酰化、硫酸化和葡萄糖苷酸化等结合反应，从而在体内和体外产生一系列复杂的代谢物。

MeIQ is metabolized along a number of pathways, including N-hydroxylation, aromatic hydroxylation and conjugation reactions of acetylation, sulfation and glucuronidation, to produce a complex array of metabolites both in vivo and in vitro.

来源:Hazardous Substances Data Bank (HSDB)

代谢

一旦被吸收，MeIQ通过N-羟基化激活为它的致突变和反应性形式，主要由人类肝细胞色素P450同种酶P450 IA2激活，在一定程度上也由P450 IA1激活。人类肝脏微粒体可以将MeIQ激活为DNA反应性物质。负责的细胞色素P450同种酶被暂时识别为CYP IA2（P450 IA2）。其他代谢途径似乎导致解毒。

Once absorbed, MeIQ is activated through N-hydroxylation to its mutagenic and reactive form, mainly by the human hepatic cyochrome P450 isozyme P450 IA2 and to some extent by P450 IA1. Human liver microsomes can activate MeIQ into a DNA-reactive species. The cytochrome P450 isozyme responsible has been identified tentatively as CYP IA2 (P450 IA2). Other metabolic pathways appeared to result in detoxication.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

人类中关于MeIQ致癌性的证据不足。在实验动物中关于MeIQ致癌性的证据充分。总体评估：MeIQ（2-氨基-3,4-二甲基咪唑[4,5-f]喹啉）可能对人类致癌（2B组）。

There is inadequate evidence in humans for the carcinogenicity of MeIQ. There is suffcient evidence in experimental animaIs for the carcinogenicity of MeIQ. Overall evaluation: MeIQ (2-Amino-3,4-dimethylimidazo(4,5-f)quinoline) is possibly carcinogenic to humans (Group 2B).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

根据实验动物中充分的致癌性证据和支持的遗传毒性数据，可以合理预期MeIQ是一种人类致癌物。[美国卫生与公共服务部/国家毒理学计划；第十一份致癌物报告：2-氨基-3,4-二甲基咪唑]

MeIQ is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity in experimental animals and supporting genotoxicity data.[DHHS/National Toxicology Program; Eleventh Report on Carcinogens: 2-Amino-3,4-Dimethylimidazo

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：偶氮甲苯

IARC Carcinogenic Agent:MeIQ

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：2B组：可能对人类致癌

IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第7卷补充：致癌性的总体评估：更新国际癌症研究机构专著第1至42卷，1987年；440页；ISBN 92-832-1411-0（已绝版）

IARC Monographs:Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

在小鼠中，静脉注射的（14）C-MeIQ迅速分布到肝脏、肾脏、胃、淋巴组织和内分泌组织。MeIQ穿过胎盘到达怀孕的NMRl小鼠的胎儿，但在24小时后胎儿组织中没有保留放射性标记。

ln mice, intravenously administered (14)C-MeIQ was distributed rapidly to the liver, kidney, stomach, lymphomyeloid tissues and endocrine tissues. MeIQ crossed the placenta to reach the fetus in pregnant NMRl mice, but no radiolabel was retained in fetal tissues after 24 hr.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

对雄性和雌性大鼠中(14C)-标记的2-氨基-3-甲基咪唑[4,5-f]喹啉(IQ)和2-氨基-3,4-二甲基咪唑[4,5-f]喹啉(MeIQ)的吸收和排泄进行了研究。排泄是迅速的，在24小时内，超过90%的放射性物质已经离开了大鼠。72小时后，两种化合物的粪便排泄大约为45-65%，相应的通过尿液排泄的量达到了37-49%。只有1-2%留在了尸体中，而在呼出的空气中发现的不到0.2%。在另一项24小时的研究中，约70%的IQ和80%的MeIQ在胆汁中找到。这两种化合物的胆汁排泄模式不同，胆汁的诱变性与放射性物质的排泄密切相关。

The absorption and excretion of (14C)-labelled 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) were studied in rats of both sexes. The excretion was rapid, and within 24 hr more than 90% of the radioactivity had left the rats. After 72 hr the fecal excretion of both compounds was approximately 45-65% and the corresponding excretion via the urine amounted to 37-49%. Only 1-2% was left in the carcasses and less than 0.2% was found in the expired air. About 70% of the IQ and 80% of the MeIQ was found in the bile fluid in a separate 24-hr study. The two compounds had different biliary excretion patterns and the mutagenicity of the bile correlated closely with the excretion of radioactivity.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  T
• 海关编码：
  2933990090

制备方法与用途

类别：有毒物品

可燃性危险特性：

• 可燃；燃烧产生有毒氮氧化物烟雾

储运特性：

• 库房应通风、低温且干燥

灭火剂：

• 干粉、泡沫、砂土、二氧化碳，以及雾状水

反应信息

• 作为反应物：
  描述：

  、 2-氨基-3,4-二甲基-3H-咪唑并喹啉 在 tris-(dibenzylideneacetone)dipalladium(0) 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 以94%的产率得到
  参考文献：
  名称：

  2'-脱氧鸟苷的PhIP加合物的合成及其掺入寡聚DNA中。

  摘要：

  膳食诱变剂2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）的2'-脱氧鸟苷加合物已经合成，并通过固态合成技术掺入DNA中。获得C8-dG加合物的关键步骤是通过适当保护的8-溴-2'-脱氧鸟嘌呤衍生物进行PhIP的钯（黄磷螯合）催化的N-芳基化（Buchwald-Hartwig反应）。反应以良好的收率进行而没有复杂的副产物，并且通过标准方法将加合物转化为所需的5'-O-DMT-3'-O-亚磷酰胺。该修饰的脱氧核苷用于合成三个寡聚脱氧核苷酸，其中在单个位点掺入了C8-PhIP-dG加合物。通过反相HPLC纯化低聚物，并通过质谱法表征。

  DOI：

  10.1021/tx0600191
• 作为产物：
  描述：

  7-methyl-6-formamidoquinoline 在 盐酸 、 lithium aluminium tetrahydride 、 硫酸 、 硝酸 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 4.0h， 生成 2-氨基-3,4-二甲基-3H-咪唑并喹啉
  参考文献：
  名称：

  Synthesis of mutagenic heteroaromatics: 2-Aminoimidazo(4,5-f)quinolines.

  摘要：

  合成了两种强效的诱变剂，2-氨基-3-甲基咪唑[4, 5-f]喹啉和2-氨基-3, 4-二甲基咪唑[4, 5-f]喹啉。

  DOI：

  10.1248/cpb.30.1857

文献信息

• Syntheses of 2-Amino-3,4-dimethyl-3<i>H</i>-imidazo[4,5-<i>f</i>]quinoline and Its Related Compounds
  作者：Hiroshi Kasai、Susumu Nishimura

  DOI：10.1246/bcsj.55.2233

  日期：1982.7

  The strongly mutagenic compound, 2-amino-3,4-dimethyl-3H-imidazo[4,5-f]quinoline (Me-IQ), isolated from broiled sardines was synthesized from 6-amino-7-methylquinoline. Several structurally related compounds were also synthesized to clarify the structure-activity relationship. Some of them also showed strong mutagenic activity towards Salmonella typhimurium TA98.

  从烤沙丁鱼中分离出强诱变化合物 2-氨基-3,4-二甲基-3H-咪唑[4,5-f]喹啉 (Me-IQ)，由 6-氨基-7-甲基喹啉合成。还合成了几种结构相关的化合物以阐明构效关系。其中一些还对鼠伤寒沙门氏菌TA98表现出强烈的诱变活性。
• STRUCTURE AND CHEMICAL SYNTHESIS OF ME-IQ, A POTENT MUTAGEN ISOLATED FROM BROILED FISH
  作者：Hiroshi Kasai、Ziro Yamaizumi、Keiji Wakabayashi、Minako Nagao、Takashi Sugimura、Shigeyuki Yokoyama、Tatsuo Miyazawa、Susumu Nishimura

  DOI：10.1246/cl.1980.1391

  日期：1980.11.5

  Structure of a mutagenic compound (Me-IQ) isolated from broiled fish was determined to be 2-amino-3,4-dimethylimidazo[4,5-f]quinoline based on the mass-, UV- and 1H-NMR-spectra and chemical synthesis. Me-IQ showed strong mutagenic activity towards Salmonella typhimurium TA98 in the presence of S-9 mix.

  从烤鱼中分离出的致突变化合物 (Me-IQ) 的结构被确定为 2-氨基-3,4-二甲基咪唑并[4,5-f]喹啉，基于质谱、UV-和 1H-NMR-光谱和化学合成。在 S-9 混合物的存在下，Me-IQ 对鼠伤寒沙门氏菌 TA98 显示出强烈的诱变活性。
• METHOD FOR PRODUCTION OF ANTIMUTAGENIC SUBSTANCE USING LACTIC ACID BACTERIUM
  申请人：Fujita Minoru

  公开号：US20100143965A1

  公开（公告）日：2010-06-10

  Disclosed is a method for producing an antimutagenic substance by using a lactic acid bacterium, which can produce the antimutagenic substance in a large quantity in an extremely simple manner and is economically advantageous; particularly a method for producing an antimutagenic substance effective for a carcinogenic substance, particularly a heterocyclic amine (HCA) which is a carcinogenic substance derived from a food, by using a lactic acid bacterium. Specifically disclosed is a method for producing an antimutagenic substance by using a lactic acid bacterium, which is characterized by suspending the lactic acid bacterium in a poorly nutrient or nutrient-free medium and leaving the lactic acid bacterium in the medium. Preferably, the poorly nutrient or nutrient-free medium is selected from the group consisting of physiological saline, a phosphate-buffered saline without a calcium or magnesium salt (PBS (−)), a citrate buffer, a distilled water, an ion-exchanged water, a natural water, a well water, a tap water, a mineral-added water, a vitamin-added water, an ion supply beverage for an athlete and the like. More preferably, the lactic acid bacterium is Lactobacillus plantarum strain KK-2503 or Lactobacillus alimentarius strain KN-15.

  本发明揭示了一种使用乳酸菌制备抗突变物质的方法，该方法可以以极其简单的方式大量生产抗突变物质，具有经济优势；特别是一种使用乳酸菌制备抗癌物质的方法，特别是一种来自食物的致癌物质，如杂环胺（HCA）的抗突变物质。具体揭示了一种使用乳酸菌制备抗突变物质的方法，其特征在于将乳酸菌悬浮在营养不良或无营养的培养基中，并将乳酸菌留在培养基中。最好选择营养不良或无营养的培养基，包括生理盐水、不含钙或镁盐的磷酸盐缓冲盐水（PBS（−））、柠檬酸盐缓冲液、蒸馏水、离子交换水、天然水、井水、自来水、矿物质添加水、维生素添加水、运动员离子供应饮料等。更好的是，乳酸菌是植物乳杆菌KK-2503菌株或食品乳杆菌KN-15菌株。
• sYCLIC PHENOL SULFIDE-METAL COMPLEXES, CATALYSTS COMPRISING THE SAME AND ANALYTICAL METHODS FOR HYDROGEN PEROXIDE
  申请人：Cosmo Research Institute

  公开号：EP1123930A1

  公开（公告）日：2001-08-16

  Provided is a metal complex which can be used in applications, such as catalysts for various chemical reactions, information/electronic materials, and the like, and which especially has a peroxidase-like activity and a high activity in phosphodiester hydrolysis. Also, provided is a novel method for analyzing a hydrogen peroxide using a metal complex having a peroxidase-like activity. A cyclic phenol sulfide metal complex is produced by bringing a cyclic phenol sulfide metal complex represented by the formula with at least one selected from metals of the Groups 8, 1A to 7A, 1B and 3B, and is used as a catalyst for oxidation by hydrogen peroxide or a catalyst for hydrolysis of phosphodiester. Furthermore, hydrogen peroxide is analyzed using the catalyst for hydrolysis. (wherein X1 represents a hydrogen atom, a hydrocarbon group, a carboxyalkyl group, or a carbamoylalkyl group; Y1 represents a hydrogen atom, a hydrocarbon group, a halogenated hydrocarbon group, a halogen atom, an acyl group, a hydroxyl group, a carboxyl group, an amido group, an amino group, a nitro group, a cyano group, a chlorosulfonic acid group, an alkoxysulfonyloxy group, or a sulfonic acid group; Z1 represents Sm1, SO, or SO2; m1 is an integer of from 1 to 7; n1 is an integer of from 4 to 8).

  本发明提供了一种金属络合物，可用于各种化学反应催化剂、信息/电子材料等应用，尤其具有过氧化物酶样活性和较高的磷酸二酯水解活性。此外，还提供了一种使用具有过氧化物酶样活性的金属复合物分析过氧化氢的新方法。通过将式中代表的环状苯酚硫化物金属络合物与至少一种选自第 8、1A 至 7A、1B 和 3B 族的金属结合，制得环状苯酚硫化物金属络合物，并将其用作过氧化氢氧化催化剂或磷酸二酯水解催化剂。此外，使用该水解催化剂分析过氧化氢。 (其中 X1 代表氢原子、烃基、羧基或氨基甲酰基；Y1代表氢原子、烃基、卤代烃基、卤素原子、酰基、羟基、羧基、氨基、氨基、硝基、氰基、氯磺酸基、烷氧基磺酰氧基或磺酸基；Z1代表Sm1、SO或SO2；m1为1至7的整数；n1为4至8的整数）。
• Method for analyzing hydrogen peroxide with a catalyst comprising a cyclic phenol sulfide metal complex
  申请人：Cosmo Research Institute

  公开号：EP1327618A1

  公开（公告）日：2003-07-16

  Provided is a novel method for analyzing a hydrogen peroxide using a metal complex having a peroxidase-like activity. A cyclic phenol sulfide metal complex is obtainable by bringing a cyclic phenol sulfide metal complex represented by the formula with at least one selected from metals of the Groups 8, 1A to 7A, 1B and 3B, and is used as a catalyst for oxidation by hydrogen peroxide. Furthermore, hydrogen peroxide is analyzed using the catalyst for hydrolysis. (wherein X1 represents a hydrogen atom, a hydrocarbon group, a carboxyalkyl group, or a carbamoylalkyl group; Y1 represents a hydrogen atom, a hydrocarbon group, a halogenated hydrocarbon group, a halogen atom, an acyl group, a hydroxyl group, a carboxyl group, an amido group, an amino group, a nitro group, a cyano group, a chlorosulfonic acid group, an alkoxysulfonyloxy group, or a sulfonic acid group; Z1 represents Sm1, SO, or SO2; m1 is an integer of from 1 to 7; n1 is an integer of from 4 to 8).

  本发明提供了一种利用具有类似过氧化物酶活性的金属络合物分析过氧化氢的新方法。通过将式中代表的环状苯酚硫化物金属络合物与至少一种选自第 8、1A 至 7A、1B 和 3B 族金属的金属结合，可获得环状苯酚硫化物金属络合物，并将其用作过氧化氢氧化的催化剂。此外，使用该催化剂分析过氧化氢的水解作用。 (其中 X1 代表氢原子、烃基、羧基或氨基甲酰基；Y1代表氢原子、烃基、卤代烃基、卤素原子、酰基、羟基、羧基、氨基、氨基、硝基、氰基、氯磺酸基、烷氧基磺酰氧基或磺酸基；Z1代表Sm1、SO或SO2；m1为1至7的整数；n1为4至8的整数）。