1,2,3,4-四氯二苯并-对-二恶英 | 30746-58-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶英
• 中文名称: 1,2,3,4-四氯二苯并-对-二恶英
• 中文别名: 1,2,3,4-四氯二苯并对二噁英
• 英文名称: 1,2,3,4-tetrachloro-dibenzo[1,4]dioxine
• 英文别名: tetrachloro-dibenzo-p-dioxin；1,2,3,4-Tetrachlorodibenzo-p-dioxin；1,2,3,4-tetrachlorodibenzodioxin；1,2,3,4-tetrachlorodioxine；1,2,3,4-PCDD；tetrachlorodibenzo-p-dioxin
• CAS: 30746-58-8
• 化学式: C₁₂H₄Cl₄O₂
• 分子量: 321.975
• InChiKey: DJHHDLMTUOLVHY-UHFFFAOYSA-N

物化性质

• 熔点：
  189°C
• 沸点：
  407.62°C (rough estimate)
• 密度：
  1.6430 (estimate)
• 物理描述：
  1,2,3,4-tetrachlorodibenzo-p-dioxin appears as colorless needles or white powder. (NTP, 1992)
• 溶解度：
  1.96e-09 M
• 蒸汽压力：
  4.80e-08 mmHg
• 亨利常数：
  2.00e-05 atm-m3/mole
• 大气OH速率常数：
  8.50e-13 cm3/molecule*sec
• 保留指数：
  2340;2340;2379;2379;2379;2379;2402;2402;386.063

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

CDDs通过口服、吸入和皮肤暴露途径被吸收。CDDs通过血清脂质和脂蛋白在血浆中运输，主要分布到肝脏和脂肪组织。CDDs通过微粒体单加氧酶系统非常缓慢地被代谢为极性代谢物，这些代谢物可以与葡萄糖醛酸和谷胱甘肽发生结合反应。它们可能通过诱导I相和II相酶来增加自己的代谢速率。CDDs的主要排泄途径是胆汁和粪便，尽管也有少量通过尿液和哺乳排出。

CDDs are absorbed through oral, inhalation, and dermal routes of exposure. CDDs are carried in the plasma by serum lipids and lipoproteins, distributing mainly to the liver and adipose tissue. CDDs are very slowly metabolized by the microsomal monooxygenase system to polar metabolites that can undergo conjugation with glucuronic acid and glutathione. They may increase the rate of their own metabolism by inducing both phase I and phase II enzymes. The major routes of excretion of CDDs are the bile and the faeces, though smaller amounts are excreted in the urine and via lactation. (L177)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

CDDs通过结合芳基烃受体并随后改变某些基因的转录来产生其毒性作用。对Ah受体的亲和力取决于特定CDD的结构。基因表达的改变可能源于Ah受体及其异二聚体形成伙伴芳基烃受体核移位子的直接相互作用，以及基因调控元件的启动或随后激活其他转录因子的磷酸化/脱磷酸化级联。受影响的基因包括几个癌基因、生长因子、受体、激素和药物代谢酶。这些基因的转录/翻译改变被认为是CDDs大多数毒性作用的原因。

CDDs cause their toxic effects by binding to the aryl hydrocarbon receptor and subsequently altering the trascription of certain genes. The affinity for the Ah receptor depends on the structure of the specific CDD. The change in gene expression may result from the direct interaction of the Ah receptor and its heterodimer-forming partner, the aryl hydrocarbon receptor nuclear translocator, with gene regulatory elements or the initiation of a phosphorylation/dephosphorylation cascade that subsequently activates other transcription factors. The affected genes include several oncogenes, growth factors, receptors, hormones, and drug-metabolizing enzymes. The change in transcription/translation of these genes is believed to be the cause of most of the toxic effects of CDDs. (L177)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

3, 其对人类致癌性无法分类。

3, not classifiable as to its carcinogenicity to humans. (L135)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

暴露于大量氯代二苯并二噁烷（CDDs）会引起氯痤疮，这是一种严重的皮肤疾病，其症状类似于粉刺，主要发生在面部和上半身。CDDs还可能引起肝损伤，并导致长期的葡萄糖代谢改变和激素水平的微妙变化。此外，研究表明CDDs可能会破坏内分泌系统，削弱免疫系统，以及造成生殖损害和出生缺陷、中枢和周围神经系统病理变化、甲状腺疾病、子宫内膜异位症和糖尿病。(L177, L178)

Exposure to large amounts of CDDs causes chloracne, a severe skin disease with acne-like lesions that occur mainly on the face and upper body. CDDs may also cause liver damage and induce long-term alterations in glucose metabolism and subtle changes in hormonal levels. In addition, studies have shown that CDDs may disrupt the endocrine system and weaken the immune system, as well as cause reproductive damage and birth defects, central and peripheral nervous system pathology, thyroid disorders, endometriosis, and diabetes. (L177, L178)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服（L177）；吸入（L177）；皮肤（L177）

Oral (L177) ; inhalation(L177) ; dermal (L177)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

除了氯痤疮，CDD暴露还会导致皮肤疹、色素沉着和体毛过多。

In addition to chloracne, CDD exposure causes skin rashes, discoloration, and excessive body hair. (L177)

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 危险等级：
  6.1(a)
• 海关编码：
  2932999060
• 危险类别：
  6.1(a)
• 危险品运输编号：
  UN 2811

反应信息

• 作为反应物：
  描述：

  1,2,3,4-四氯二苯并-对-二恶英 在 硝酸 、 溶剂黄146 作用下， 以79%的产率得到2-nitro-6,7,8,9-tetrachlorodibenzo-p-dioxin
  参考文献：
  名称：

  Kuntsevich, A.D.; Golovkov, V.F.; Ivanov, K.N., Russian Journal of General Chemistry, 1994, vol. 64, # 10.2, p. 1532 - 1538

  摘要：

  DOI：
• 作为产物：
  描述：

  五氯酚 生成 1,2,3,4-四氯二苯并-对-二恶英
  参考文献：
  名称：

  DICKSON, L. C.;LENOIR, D.;HUTZINGER, O., CHEMOSPHERE, 19,(1989) N-9, C. 1435-1445

  摘要：

  DOI：

文献信息

• Copper-catalyzed chlorination and condensation of acetylene and dichloroacetylene
  作者：Philip H. Taylor、Andreas Wehrmeier、Sukh S. Sidhu、Dieter Lenoir、K.-W. Schramm、A. Kettrup

  DOI：10.1016/s0045-6535(99)00272-6

  日期：2000.6

  The chlorination and condensation of acetylene at low temperatures is demonstrated using copper chlorides as chlorinated agents coated to model borosilicate surfaces. Experiments with and without both a chlorine source and borosilicate surfaces indicate the absence of gas-phase and gas-surface reactions. Chlorination and condensation occur only in the presence of the copper catalyst. C2 through C8

  使用氯化铜作为模拟硼硅酸盐表面的氯化剂，证明了乙炔在低温下的氯化和缩合。在有和没有氯源和硼硅酸盐表面的情况下进行的实验表明，没有气相和气相表面反应。氯化和缩合仅在铜催化剂存在下发生。在废水中观察到C2至C8有机产物。仅从提取硼硅酸盐表面观察到PCDD / F。提出了与观察到的产物分布一致的全局反应模型。用二氯乙炔进行的类似实验表明，在不存在铜催化剂的情况下，反应性更高。在低温下在气相中和在存在硼硅酸盐表面的情况下观察到反应。仅在铜催化剂存在下观察到六氯苯的形成。仅从提取硼硅酸盐表面观察到PCDD / F。提出了一种由二氯乙炔形成六氯苯的整体反应模型。
• Phenothiazine derivatives and their method of use
  申请人：Rozman K. Karl

  公开号：US20050288279A1

  公开（公告）日：2005-12-29

  Novel phenothiazine derivatives and their use in the treatment of diabetes mellitus (type I and type II), and as an ovulation inhibitor (contraceptive), cancer chemotherapeutic and/or prophylactic agent, anti-obesity drug (body weight regulator), and immunostimulant.

  新型苯并噻嗪衍生物及其在糖尿病（I型和II型）治疗、作为排卵抑制剂（避孕药）、癌症化疗和/或预防药、抗肥胖药（体重调节剂）和免疫刺激剂方面的应用。
• 4-(c2-6alkoxy)-substituted chalcones as therapeutic agents
  申请人：——

  公开号：US20040259957A1

  公开（公告）日：2004-12-23

  The present invention pertains to compounds of the following formula: (1) wherein: R ALK is primary or secondary aliphatic saturated C 2-6 alkyl; each of R B2 , R B3 , R B4 , and R B5 is independently —H, —OH, or —OMe; each of R 1 and R 2 is independently: —H, optionally substituted C 1-4 alkyl, or optionally substituted C 5-20 aryl; R A3 is —H, —OH, —OC(═O)RE, —OS(═O) 2 OH, or —OP(═O)(OH) 2 ; R E is: —H, optionally substituted C 1-6 alkyl, optionally substituted C 3-20 heterocyclyl, or optionally substituted C 5-20 aryl; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, for both diagnosis and treatment of, for example, proliferative conditions, such as cancer, and inflammatory conditions. 1

  本发明涉及以下式的化合物：（1） 其中：RALK是一级或二级脂肪饱和C2-6烷基；RB2、RB3、RB4和RB5中的每一个独立地是—H、—OH或—OMe；R1和R2中的每一个独立地是：—H、可选地取代的C1-4烷基或可选地取代的C5-20芳基；RA3是—H、—OH、—OC(═O)RE、—OS(═O)2OH或—OP(═O)(OH)2；RE是：—H、可选地取代的C1-6烷基、可选地取代的C3-20杂环基或可选地取代的C5-20芳基；或其药学上可接受的盐、溶剂化物、酰胺、酯、醚、化学保护形式或前药。本发明还涉及包含这种化合物的制药组合物，以及这种化合物和组合物的使用，无论是体外还是体内，用于诊断和治疗增生性疾病，例如癌症和炎症性疾病。
• 3, 4-Methylenedioxy-substituted chalcones as therapeutic agents
  申请人：——

  公开号：US20040254149A1

  公开（公告）日：2004-12-16

  The present invention pertains to the use of a compounds for the manufacture of a medicament for use in the treatment of a proliferative condition, wherein the compounds have the following formula: 1 wherein: each of R B2 , R B3 , R B4 , and R B5 is independently —H, —OH, or —OMe; each of R 1 and R 2 is independently: —H, optionally substituted C 1-4 alkyl, or optionally substituted C 5-20 aryl; R A3 is —H, —OH, —OC(═O)R E , —OS(═O) 2 OH, or —OP(═O)(OH) 2 ; R E is: —H, optionally substituted C 1-6 alkyl, optionally substituted C 3-20 heterocyclyl, or optionally substituted C 5-20 aryl; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug thereof. The present invention also pertains to such compounds, pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, for both diagnosis and treatment of, for example, proliferative conditions, such as cancer, and inflammatory conditions.

  本发明涉及使用某些化合物制备药物，用于治疗增殖性疾病，其中该化合物具有以下结构式：1其中：RB2、RB3、RB4和RB5中的每一个独立地为—H、—OH或—OMe；R1和R2中的每一个独立地为—H、选择性地取代的C1-4烷基或选择性地取代的C5-20芳基；RA3为—H、—OH、—OC(═O)RE、—OS(═O)2OH或—OP(═O)(OH)2；RE为：—H、选择性地取代的C1-6烷基、选择性地取代的C3-20杂环基或选择性地取代的C5-20芳基；或其药学上可接受的盐、溶剂化物、酰胺、酯、醚、化学保护形式或前药。本发明还涉及这些化合物、包含这些化合物的药物组成物，以及这些化合物和组成物的使用，无论是在体内还是体外，用于诊断和治疗增殖性疾病，例如癌症和炎症性疾病。
• Compounds that act to modulate insect growth and methods and systems for identifying such compounds
  申请人：Henrich C. Vincent

  公开号：US20050049230A1

  公开（公告）日：2005-03-03

  Disclosed are methods and systems for screening for compounds that act to modulate insect growth. Bioassays including cell culture and/or transgenic insects engineered with various components of the ecdysoid receptor (EcR) and/or the farsenoid-X receptor (RXR) systems to identify compounds that act as insecticides and/or hormone receptor activators are described. Also described are compounds, and compositions, identified as being putative insecticides based upon their ability to activate EcR and/or FXR mediated transcription.

  本发明涉及筛选调节昆虫生长的化合物的方法和系统。描述了生物测定法，包括细胞培养和/或转基因昆虫，这些昆虫经过工程改造，具有ecdysoid受体（EcR）和/或farsenoid-X受体（RXR）系统的各种组分，以识别作为杀虫剂和/或激素受体激活剂的化合物。还描述了被鉴定为潜在杀虫剂的化合物和组合物，这些化合物和组合物的鉴定基于它们激活EcR和/或FXR介导的转录的能力。

表征谱图