6-methyl-1,3,8-trichlorodibenzofuran | 118174-38-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 6-methyl-1,3,8-trichlorodibenzofuran
• 英文别名: 1,3,8-trichloro-6-methyldibenzofuran
• CAS: 118174-38-2
• 化学式: C₁₃H₇Cl₃O
• 分子量: 285.557
• InChiKey: RPMARRQIRRJWEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  13.1
• 氢给体数：
  0
• 氢受体数：
  1

ADMET

代谢

在现有文献中没有找到关于二苯并呋喃在哺乳动物体内的代谢信息。细菌Sphingomonas、Brevibacterium、Terrabacter和Staphylococcus auricularis通过二苯并呋喃4,4a-二加氧酶将二苯并呋喃降解为2,2',3-三羟基联苯。

No information on the metabolism of dibenzofuran in mammalian organisms was found in the available literature. The bacteria Sphingomonas, Brevibacterium, Terrabacter, and Staphylococcus auricularis degrade dibenzofuran to 2,2',3-trihydroxybiphenyl via dibenzofuran 4,4a-dioxygenase. (L952)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

卤素代二苯并呋喃（多氯二苯并呋喃PCDFs和多溴二苯并呋喃PBDFs）能与芳香烃受体（AhR）结合，增强了其激活XRE（外源化学物反应元件）启动子区域的转录能力。特别是AhR与PCDF结合后，将其转移到细胞核中，并与芳香烃核转位蛋白（ARNT）和外来化合物反应元件（XRE）共同作用，增加了CYP1A1和芳香烃羟化酶（CYP1B1）的表达。AhR信号通路还能通过环氧合酶-2增加花生四烯酸转化为前列腺素的过程，改变Wnt/β-连环蛋白信号通路，下调Sox9的表达，并改变炎症细胞因子受体的信号传导。AhR信号还能改变类固醇激素受体的蛋白酶体降解，改变细胞对UVB应激的反应，并改变某些T细胞亚群的分化。这些由AhR介导的激活和改变会导致体重减轻、癌症和胸腺萎缩（这是免疫和内分泌紊乱的特征），这些都是PCDFs和相关有毒卤素代芳香烃的常见毒性反应。

Halogenated dibenzofurans (PCDFs and PBDFs) bind the aryl hydrocarbon receptor (AhR), which increases its ability to activate transcription in the XRE (xenobiotic resoponse element) promoter region. Specifically AhR binds to the PCDF, translocates it to the nucleus and together with hydrocarbon nuclear translocator (ARNT) and xenobiotic responsive element (XRE) increases the expression of CYP1A1 and aryl hydrocarbon hydroxylase (CYP1B1). AhR signaling also increseases conversion of arachidonic acid to prostanoids via cyclooxygenase-2, alters Wnt/beta-catenin signaling downregulating Sox9 and alters signaling by receptors for inflammatory cytokines. AhR signalling also alters proteasomal degradation of steroid hormone receptors, alters cellular UVB stress response and changes the differentiation of certain T-cell subsets. The resulting AhR mediated activation and alteration leads to body weight loss, cancer and thymic atrophy (characteristic of immune and endocrine disruption) which are common toxic responses to PCDFs and related toxic halogenated aryl hydrocarbons.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

无致癌性迹象（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity (not listed by IARC). (L135)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

CDFs会导致呕吐和腹泻、贫血、更频繁的肺部感染、麻木以及对神经系统等其他影响，以及肝脏的轻微变化。然而，在摄入CDFs的人群中没有发现永久性的肝脏变化或明确的肝脏损伤。

CDFs cause vomiting and diarrhea, anemia, more frequent lung infections, numbness and other effects on the nervous system, and mild changes in the liver. However, there were no permanent liver changes or definite liver damage found in people who ingested CDFs. (L952)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

吸入 (L952) ; 皮肤 (L952) ; 口服 (L952)

Inhalation (L952) ; dermal (L952) ; oral (L952)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

皮肤和眼部刺激，尤其是严重的痤疮、肤色变黑和带有分泌物的肿胀眼睑是CDF中毒最明显的健康影响。

Skin and eye irritations, especially severe acne, darkened skin color, and swollen eyelids with discharge are the most obvious health effects of the CDF poisoning. (L952)

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为产物：
  描述：

  4-氯-2-甲基苯酚 、 2,4,6-三氯苯胺 、 硝酸异戊酯 在 苯酚 、 silica gel 、 二甲基亚砜 、 potassium carbonate 、 6-methyl-1,3,8-trichlorodibenzofuran 、 petroleum spirit 、 Anisole methanol 作用下， 反应 20.5h， 以gave (in CDCL3)的产率得到6-methyl-1,3,8-trichlorodibenzofuran
  参考文献：
  名称：

  Synthesis and application of alkyl-substituted dibenzofurans as

  摘要：

  提供了一种通过给予生物活性量的取代二苯并呋喃或取代二苯并二氧杂环来抑制雌激素活性的方法。

  公开号：

  US05516790A1
• 作为试剂：
  描述：

  4-氯-2-甲基苯酚 、 2,4,6-三氯苯胺 、 硝酸异戊酯 在 苯酚 、 silica gel 、 二甲基亚砜 、 potassium carbonate 、 6-methyl-1,3,8-trichlorodibenzofuran 、 petroleum spirit 、 Anisole methanol 作用下， 反应 20.5h， 以gave (in CDCL3)的产率得到6-methyl-1,3,8-trichlorodibenzofuran
  参考文献：
  名称：

  Synthesis and application of alkyl-substituted dibenzofurans as

  摘要：

  提供了一种通过给予生物活性量的取代二苯并呋喃或取代二苯并二氧杂环来抑制雌激素活性的方法。

  公开号：

  US05516790A1

文献信息

• SYNTHESIS OF DIINDOLYLMETHANES AND INDOLO[3,2-B]CARBAZOLES, COMPOUNDS FORMED THEREBY, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：Wisconsin Alumni Research Foundation

  公开号：US20160039754A1

  公开（公告）日：2016-02-11

  Described is a method to make diindolylmethanes and indolyl/pyrrolylmethanes, The method includes the steps of contacting an ether comprising an arylpropargyl moiety and an amine-protected, substituted or unsubstituted aniline moiety with a substituted or unsubstituted indol or a substituted or unsubstituted pyrrole, in the presence of a metal-containing catalyst, for a time and at a temperature to cause an annulation/arylation cascade reaction that yields a diindolylmethane or a indolyl/pyrrolylmethane. The resulting compounds are effective to modulate activity of arylhydrocarbon receptors, to inhibit activity of PCSK9, and to stimulate secretion of glucagon-like peptide 1 in mammals.

  描述了一种制备二吲哚基甲烷和吲哚基/吡咯基甲烷的方法。该方法包括以下步骤：在金属催化剂的存在下，使包含芳基炔丙基部分和胺保护的、取代的或未取代的苯胺部分的醚与取代的或未取代的吲哚或取代的或未取代的吡咯接触，接触一段时间和温度，以引发环化/芳基化级联反应，从而产生二吲哚基甲烷或吲哚基/吡咯基甲烷。所得化合物能有效调节芳基烃受体的活性，抑制PCSK9的活性，并刺激哺乳动物胰高血糖素样肽1的分泌。
• Enhancement of Natural Killer (NK) Cell Proliferation and Activity
  申请人：Gamida Cell Ltd.

  公开号：US20140023626A1

  公开（公告）日：2014-01-23

  Methods of ex-vivo culture of natural killer (NK) cells are provided and, more particularly, methods for enhancing propagation and/or functionality of NK cells by treating the cells with an aryl hydrocarbon antagonist in combination with cytokines driving NK cell proliferation. Also envisioned are compositions comprising cultured NK cells and therapeutic uses thereof.

  提供了自体培养自然杀伤细胞（NK细胞）的方法，更具体地，通过将细胞与芳香族碳氢化合物拮抗剂和促进NK细胞增殖的细胞因子联合处理，提高NK细胞的繁殖和/或功能。此外，还设想了包含培养的NK细胞的组合物及其治疗用途。
• Methods of Culturing and Expanding Mesenchymal Stem Cells and Isolated Cell Populations Generated Thereby
  申请人：Gamida Cell Ltd.

  公开号：US20140023623A1

  公开（公告）日：2014-01-23

  A method of culturing mesenchymal stem cells (MSCs) is provided. The method comprising culturing a population of the MSCs in a medium comprising an aryl hydrocarbon receptor antagonist, thereby culturing MSCs.

  提供了一种培养间充质干细胞（MSCs）的方法。该方法包括在含有芳香族羟基化合物受体拮抗剂的培养基中培养MSCs的群体，从而培养MSCs。
• COMPOUNDS THAT EXPAND HEMATOPOIETIC STEM CELLS
  申请人：Boitano Anthony E.

  公开号：US20100183564A1

  公开（公告）日：2010-07-22

  The present invention relates to compounds and compositions for expanding the number of CD34+ cells for transplantation. The invention further relates to a cell population comprising expanded hematopoietic stem cells (HSCs) and its use in autologous or allogeneic transplantation for the treatment of patients with inherited immunodeficient and autoimmune diseases and diverse hematopoietic disorders to reconstitute the hematopoietic cell lineages and immune system defense.

  本发明涉及用于扩增CD34+细胞数量的化合物和组合物。该发明进一步涉及包含扩增造血干细胞（HSCs）的细胞群体及其在自体或异体移植中的使用，用于治疗遗传性免疫缺陷和自身免疫性疾病以及不同的造血障碍，以重建造血细胞系和免疫系统防御。
• EXPANDED HEMATOPOIETIC STEM CELLS FROM CORD BLOOD AND THEIR THERAPEUTIC USE
  申请人：Novartis AG

  公开号：EP3524604A1

  公开（公告）日：2019-08-14

  The present invention relates to compounds and compositions for expanding the number of CD34+ cells for transplantation. The invention further relates to a cell population comprising expanded hematopoietic stem cells (HSCs) and its use in autologous or allogeneic transplantation for the treatment of patients with inherited immunodeficient and autoimmune diseases and diverse hematopoietic disorders to reconstitute the hematopoietic cell lineages and immune system defense.

  本发明涉及用于扩大移植用CD34+细胞数量的化合物和组合物。本发明进一步涉及由扩增的造血干细胞（HSCs）组成的细胞群及其在自体或异体移植中的用途，用于治疗遗传性免疫缺陷和自身免疫性疾病以及各种造血疾病患者，以重建造血细胞系和免疫系统防御。