2,3,4,7,8-五氯二苯并呋喃 | 57117-31-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 中文名称: 2,3,4,7,8-五氯二苯并呋喃
• 中文别名: 2,3,4,7,8--五氯二苯并对二恶英
• 英文名称: 2,3,4,7,8-pentachlorodibenzofuran
• 英文别名: 2,3,4,7,8-pentachlorodibenzodioxin；1,2,3,7,8-pentachlorodibenzofuran；2,3,4,7,8-pentachlorinated dibenzofuran；2,3,4,7,8-PeCDF
• CAS: 57117-31-4
• 化学式: C₁₂H₃Cl₅O
• 分子量: 340.42
• InChiKey: OGBQILNBLMPPDP-UHFFFAOYSA-N

物化性质

• 物理描述：
  2,3,4,7,8-pentachlorodibenzofuran is a solid. (NTP, 1992)
• 熔点：
  196.0 °C
• 溶解度：
  In water, 0.000235 mg/liter @ 23 °C
• 蒸汽压力：
  2.63X10-9 mm Hg @ 25 °C
• 保留指数：
  2536;2545;2586;2551;2551

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 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：
  13.1
• 氢给体数：
  0
• 氢受体数：
  1

ADMET

代谢

在多氯二苯并呋喃（pentaCDFs）中，1,2,3,4,8-、1,2,3,7,8-和2,3,4,7,8-多氯二苯并呋喃的转化率分别为高、中、低。1,2,3,7,8-多氯二苯并呋喃的主要代谢物（在7种发现的化合物中）是羟基多氯二苯并呋喃。据调查者称，可能还形成了6,7-二羟基多氯二苯并呋喃。还鉴定出了四氯化物。1,2,3,7,8-多氯二苯并呋喃的主要代谢物（在12种发现的化合物中）是二羟基多氯二苯并呋喃；其他衍生物包括单羟基四氯和五氯二苯并呋喃以及三氯二羟基二苯并呋喃。2,3,4,7,8-多氯二苯并呋喃的代谢导致了2种主要化合物（在10种发现的化合物中），一种甲氧基多氯二苯并呋喃和一个二甲氧基五氯联苯，后者是通过醚键断裂形成的。还发现了一种含硫代谢物。未代谢的多氯二苯并呋喃也随胆汁排出。从1,2,3,6,7,8-六氯二苯并呋喃中只鉴定出了少量的羟基多氯二苯并呋喃，而1,2,3,4,6,7-七氯二苯并呋喃没有检测到代谢物。/多氯二苯并呋喃/

Among the pentaCDFs, the rate of transformation of 1,2,3,4,8-, 1,2,3,7,8-, and 2,3,4,7,8-pentaCDF was high, moderate, and low, respectively. The predominant metabolite (out of 7 compounds found) of 1,2,3,7,8-pentaCDF was a hydroxy-pentaCDF. According to investigators, formation of 6,7-dihydroxy-pentaCDF may also have occurred. Tetrachlorinated compounds were also identified. The major metabolite (out of 12 compounds found) of 1,2,3,7,8-pentaCDF was a dihydroxy-pentaCDF; other derivatives included monohydroxy-tetra- and pentaCDFs and a trichloro-dihydroxyCDF. Metabolism of 2,3,4,7,8-pentaCDF led to 2 major compounds (out of 10 compounds found), a methoxy-pentaCDF, and a dimethoxy-pentachlorobiphenyl, the latter formed by ether cleavage. A sulfur containing metabolite was also present. Unmetabolized pentaCDFs were also excreted in the bile. Only a small amount of a hydroxy-pentaCDF was identified from 1,2,3,6,7,8- hexaCDF, whereas no metabolites were detected from 1,2,3,4,6,7-heptaCDF. /Pentachlorodibenzofurans/

来源:Hazardous Substances Data Bank (HSDB)

代谢

有限的数据表明，与PCDDs相比，PCDFs确实会发生代谢的自诱导和胆汁排泄。在大鼠接受2,3,7,8-TCDF预处理（1.0微摩尔/千克，提前3天）后，随后给予的（14C）2,3,7,8-TCDF的胆汁排泄显著增加。未经处理的大鼠在最初的8小时内排泄了剂量的5.7 ± 2.4%，而预处理的大鼠排泄了（14C）2,3,7,8-TCDF的13.2 ± 3.2%。类似地，在大鼠接受2,3,4,7,8-五氯二苯并呋喃预处理（500微克/千克，口服，提前3天）后，随后给予的（14C）2,3,4,7,8-五氯二苯并呋喃的胆汁消除增加了一倍。这些结果提示，2,3,7,8-TCDF和2,3,4,7,8-五氯二苯并呋喃的预处理诱导了这些同类物的代谢。

Limited data suggest that autoinduction of metabolism and biliary excretion does occur for PCDFs, in contrast to PCDDs. Pretreatment of rats with 2,3,7,8-TCDF (1.0 umol/kg, 3 days earlier) significantly increased the biliary excretion of a subsequent dose of (14C)2,3,7,8-TCDF. The naive rats excreted 5.7 + or - 2.4% of the dose over the initial 8 hr, while the pretreated rats excreted 13.2 + or - 3.2% of the (14C)2,3,7,8-TCDF. Similarly, pretreatment of rats with 2,3,4,7,8-pentaCDF (500 ug/kg, /orally/, 3 days earlier) resulted in a two-fold increase in the biliary elimination of a subsequent dose of (14C)2,3,4,7,8-pentaCDF. These results suggest that pretreatment with 2,3,7,8-TCDF and 2,3,4,7,8-pentaCDF induces the metabolism of these congeners.

来源:Hazardous Substances Data Bank (HSDB)

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（PCDFs和PBDFs）与芳基烃受体（AhR）结合，增加了其在XRE（外源化合物响应元件）启动子区域激活转录的能力。具体来说，AhR与PCDF结合，将其转运到细胞核，并与芳烃核转运蛋白（ARNT）和外来化合物响应元件（XRE）一起增加CYP1A1和芳基烃羟化酶（CYP1B1）的表达。AhR信号还通过环氧合酶-2增加花生四烯酸转化为前列腺素，改变WNT/β-连环蛋白信号，下调Sox9，并改变炎症细胞因子受体的信号传导。AhR信号还改变类固醇激素受体的蛋白酶体降解，改变细胞的UVB应激反应，并改变某些T细胞亚群的分化。由此产生的AhR介导的激活和改变导致体重减轻、癌症和胸腺萎缩（免疫和内分泌紊乱的特征），这是对PCDFs和相关有毒卤素代芳基烃的常见毒性反应。

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

• 致癌性证据

评估：对于多氯代二噁烷的人类致癌性，人类中的证据不足。对于2,3,4,7,8-五氯代二噁烷的致癌性，实验动物中的证据有限。总体评估：多氯代二噁烷对人体致癌性无法分类（第3组）。/多氯代二噁烷/

Evaluation: There is inadequate evidence in humans for the carcinogenicity of polychlorinated dibenzofurans. There is limited evidence in experimental animals for the carcinogenicity of 2,3,4,7,8-pentachlorodibenzofuran. Overall evaluation: Polychlorinated dibenzofurans are not classifiable as to their carcinogenicity to humans (Group 3). /Polychlorinated dibenzofurans/

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：2,3,4,7,8-五氯二苯并呋喃

IARC Carcinogenic Agent:2,3,4,7,8-Pentachlorodibenzofuran

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：1类：对人类致癌

IARC Carcinogenic Classes:Group 1: 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100F卷：（2012年）化学物质及相关职业

IARC Monographs:Volume 100F: (2012) Chemical Agents and Related Occupations

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

Fischer-344雄性大鼠单次口服剂量为34-338微克/千克的14C-2,3,4,7,8-五氯二苯并呋喃，给药3天后，CDF衍生放射性在肝脏中浓度最高（>50%），其次是脂肪（6%）、皮肤（0.9%）和肌肉（0.5%）。当以每克组织的剂量百分比表示时，肝脏为5.9%，其次是脂肪为0.3%，肾上腺为0.15%。无论结果如何表示，组织分布与剂量无关，所有其他组织和器官中只有微量的放射性。.../大约/30%的CDF衍生放射性在三天的期间内通过粪便排出，与剂量无关。在呼出的空气中没有检测到放射性，尿液排泄每天占剂量的<0.01%。给药后1天对粪便样本的分析表明，>50%的CDF衍生放射性是母化合物；然而，两天后这一比例降至20%。这些结果与在大鼠中获得的四取代同系物的结果相比，表明在CDF环的第四个位置添加氯代物可以使排泄率减半。.../这与/两种同系物的代谢处理有关。/2,3,4,7,8-五氯二苯并呋喃/

Male Fischer-344 rats received a single oral dose of 14C-2,3,4,7,8-pentaCDF at 34-338 ug/kg, and 3 days after dosing, CDF-derived radioactivity was most concentrated in the liver (>50%), followed by adipose (6%), skin (0.9%), and muscle (0.5%). When expressed as percentage of the dose per gram of tissue, the liver had 5.9% followed by adipose with 0.3%, and adrenal with 0.15%. Regardless of how the results were expressed, tissue distribution was not dose-related, and all other tissues and organs had only traces of radioactivity. .../About/ 30% of the CDF-derived radioactivity was excreted in the feces over a 3 day period, regardless of the dose. No radioactivity was detected in expired air, and urinary excretion accounted for <0.01% of the dose per day. Analysis of fecal samples 1 day after dosing suggested that >50% of the CDF-derived radioactivity was parent compound; however, 2 days later this fell to 20%. These results, when compared with those obtained with the tetra-substituted congener in rats, suggest that by adding a chlorine substitute to position four in the CDF ring, excretion rate is decreased by half. .../This/ is related to the metabolic handling of the two congeners. /2,3,4,7,8-Pentachlorodibenzofuran/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

年轻雄性威斯大鼠单次口服剂量为1.0毫克/千克体重的2,3,4,7,8-五氯二苯并呋喃（2,3,4,7,8-pentaCDF），在沙拉油中给药后，吸收了大约6.8%。每日粪便排泄量约为给药剂量的0.1%，而在尿液中未检测到2,3,4,7,8-五氯二苯并呋喃。给药四周后，肝脏中2,3,4,7,8-五氯二苯并呋喃的保留量为剂量的48.8%。在给药后一周并在整个研究期间将5%的活性炭珠添加到饮食中，使2,3,4,7,8-五氯二苯并呋喃的粪便排泄量增加了大约3倍，但对尿液排泄没有影响。在基础饮食中补充活性炭珠的大鼠的肝脏和肝外组织（除肾脏外）中的2,3,4,7,8-五氯二苯并呋喃水平低于仅接受基础饮食的大鼠。

Young male Wistar rats absorbed approximately 6.8% of a single oral dose of 1.0 mg 2,3,4,7,8-pentaCDF/kg bw given in salad oil. The daily fecal excretion was about 0.1% of the administered dose/day, whereas no 2,3,4,7,8-pentaCDF was detected in urine. Four weeks after dosing the retention of 2,3,4,7,8-pentaCDF in the liver was 48.8% of the dose. The addition of 5% of activated charcoal beads to the diet, one week after dosing and throughout the study, increased the fecal elimination of 2,3,4,7,8-pentaCDF about 3-fold, but had no effect on urinary elimination. Both the liver and extrahepatic tissues, except the kidney, from rats on basal diet supplemented with activated charcoal beads had lower levels of 2,3,4,7,8-pentaCDF than rats on basal diet only. /2,3,4,7,8-Pentachlorodibenzofuran/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

2,3,4,7,8-五氯二苯并呋喃（2,3,4,7,8-pentachlorodibenzofuran）在玉米油中的口服生物利用度与TCDD相似。此外，2,3,4,7,8-五氯二苯并呋喃的吸收与剂量（0.1、0.5或1.0微摩尔/千克）无关。

The oral bioavailability of 2,3,4,7,8-pentaCDF (2,3,4,7,8-pentachlorodibenzofuran) in corn oil is similar to that of TCDD. Furthermore, 2,3,4,7,8-pentaCDF absorption was independent of the dose (0.1, 0.5, or 1.0 umol/kg).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠、豚鼠、仓鼠和小鼠的研究中发现，尿液和胆汁中排出的TCDD衍生的放射性物质几乎全部是TCDD的代谢物。肝脏和脂肪中TCDD代谢物的明显缺失表明，一旦形成，TCDD的代谢物就会迅速排出。因此，尿液和胆汁中TCDD的排出依赖于毒素的代谢。其他化合物的更有限数据也表明，这种关系可能也适用于1,2,3,7,8-五氯二苯并呋喃（pentaCDF）和2,3,4,7,8-五氯二苯并呋喃（pentaCDF）……。

Studies in the rat, guinea pig, hamster, and mouse have found that essentially all of the TCDD-derived radioactivity excreted in the urine and bile corresponds to metabolites of TCDD. The apparent absence of TCDD metabolites in liver and fat suggests that once formed, the metabolites of TCDD are excreted readily. Thus, urinary and biliary elimination of TCDD depends on metabolism of the toxin. The more limited data for other compounds also suggest that this relationship may be true for ...1,2,3,7,8-pentaCDF, /and/ 2,3,4,7,8-pentaCDF... .

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险类别：
  6.1(a)
• 危险品运输编号：
  UN 2811

反应信息

• 作为产物：
  描述：

  矮壮素 在 氧气 作用下， 生成 2,3,4,7,8-五氯二苯并呋喃
  参考文献：
  名称：

  Estimation of dioxin emission from fires in chemicals

  摘要：

  The formation of the 17 toxic 2,3,7,8-substituted PCDDs and PCDFs during combustion of selected chemicals were measured by high-resolution GC/MS. The 16 chemicals studied were commonly used chlorinated pesticides, industrial chemicals, and PVC. In a series of experiments carried out in a DIN 53,436 furnace, 2.5 g of these compounds were burned at 500 degrees C and 900 degrees C, respectively. The resultant yields ranged from 740 ng ITEQ/g for pentachlorophenol, to below 0.01 ng ITEQ/g for PVC and dichlobenil. The results show that some chemicals generate PCDD/F in very high possibly dangerous - amounts during burning, whereas others generate insignificant amounts. The influence of scale were studied for chlorobenzene and 4-chloro-3-nitro-benzoic acid in additional experiments, carried out in a cone calorimeter burning 20 g substance, and in ISO 9705 room test burning about 50 kg. A good agreement between the results for large and small scale indicated that formation of PCCD/F during a fire may be estimated from laboratory experiments. This suggest laboratory test may be used to screen for chemicals posing a hazard for release of PCDD/F during fires. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0045-6535(99)00231-3

文献信息

• On Dioxin Formation in Iron Ore Sintering
  作者：Mariusz K. Cieplik、Jose Pastor Carbonell、Christina Muñoz、Sarah Baker、Sophie Krüger、Per Liljelind、Stellan Marklund、Robert Louw

  DOI：10.1021/es026292g

  日期：2003.8.1

  sintering facility could satisfactorily imitate the large-scale process, in part or as a whole. Results obtained with realistic feed mixtures point at dioxin formation in the sinter bed at levels significant enough to explain a major part of the outputs observed in the real-life process. With approximately 8 ppm (wt) of chloride added as NaCl, the PCDD/F output doubled, but with the same proportion of

  铁矿石烧结是“二恶英”，多氯二苯并对二恶英和二苯并呋喃（PCDD / Fs）的重要来源。本文报道了尝试确定造成PCDD / F形成的材料，条件和机理的尝试（i）通过研究矿石的显着特性（即关于模型有机物的氧化，冷凝和氯化），以及（ii）使用现实生活的材料在微观尺度上模拟工业过程。采用实验设计原理（DOE）。铁矿石的反应性差异很大。褐铁矿/针铁矿“软”矿石是一种非常活泼的氧化催化剂（例如，用于苯和苯酚），该特性可用于清除粗烧结工艺废气，而赤铁矿/磁铁矿“硬”矿石则不是。后者，但是强烈促进苯酚缩合为二苯并呋喃。新建的实验室级微型烧结设备可以部分或整体令人满意地模仿大规模过程。用实际的进料混合物获得的结果表明，在烧结床中二恶英的形成水平足以说明在现实生活中观察到的大部分产出。通过添加约8 ppm（wt）的氯化物作为NaCl，PCDD / F的产量增加了一倍，但是在氯的施用比例与C2Cl4相同的情况
• PCDD/DF formations by the heterogeneous thermal reactions of phenols and their TiO2 photocatalytic degradation by batch-recycle system
  作者：Hajime Muto、Koki Saitoh、Hitoshi Funayama

  DOI：10.1016/s0045-6535(00)00552-x

  日期：2001.10

  and dibenzofurans (PCDD/DFs) formation by the thermal reactions of phenols with CuCl2 under oxygen flux were carried out in relation to their formation mechanisms. To evaluate the effect of photocatalytic degradation of titanium dioxide (TiO2) thin film prepared by the sol-gel method, the photocatalysis of PCDD/DFs in acetonitrile/water solution by batch-recycle system was conducted. For the thermal reaction

  就酚类与CuCl2在氧通量下的热反应，进行了多氯代二苯并二恶英和二苯并呋喃（PCDD / DFs）的形成机理的研究。为了评价溶胶-凝胶法制备的二氧化钛（TiO2）薄膜的光催化降解效果，采用间歇循环系统对PCDD / DFs在乙腈/水溶液中的光催化性能进行了研究。对于2,4,5-三氯苯酚（2,4,5-TCP）和CuCl2的粉末混合物的热反应系统，总PCDD /的形成速率为8.1 microg / g-2,4,5-TCP / min PCDDs的DFs和6.9 microg / g-2,4,5-TCP / min，与苯酚蒸气/氧气/ CuCl2粉末系统相比，PCDD / DF的总速率高出约40倍。对于2,4,5-TCP的系统，PCDDs主要是通过邻苯氧酚（POP）中间体通过2,4,5-三氯苯酚的缩合反应形成的。对于PCDD / DF光催化降解，大多数PCDD同系物会快速分解，并且在辐照后24小时使用由2
• Emissions of polychlorinated dibenzo-p-dioxins and dibenzofurans from catalytic and thermal oxidizers burning dilute chlorinated vapors
  作者：John R. Hart

  DOI：10.1016/j.chemosphere.2003.10.017

  日期：2004.3

  (ng/dscm)=8.4 exp(-0.0084T degrees C); (2) dioxin/furan production occurs at the combustion catalyst; (3) small variations in temperature cause large changes in the congener distribution of the dioxin and furan isomers; (4) molar TEQ yields from the parent compounds fed to the oxidizers are very small (10(-9)-10(-13)); (5) catalytic and thermal oxidizers may destroy dioxins fed from the ambient air; and (6)

  通过对低（几至几百）百万分之一的氯化和非氯化挥发性有机化合物（VOC）的氧化进行的57次现场测试，发现了多氯二苯并对二恶英和二苯并呋喃（二恶英）的排放。在使用铂，铂/钯或铬（IV）氧化物燃烧催化剂的催化氧化剂中，或在热氧化剂（无催化剂）中发生氧化。催化剂入口温度为293至573摄氏度。热氧化剂的运行温度（火焰后）为773至927摄氏度。报告了有毒的二恶英和呋喃异构体的数据，并进行了加权和表示为国际有毒当量（ 2,3,7,8-四氯二苯并-对-二恶英的TEQ）。最大烟囱排放为1.07 ng / m3 TEQ，发生在293摄氏度。该现场研究的主要结果是：（1）堆中的TEQ水平随工作温度的降低而呈指数增长，经验公式为TEQ（ng / dscm）= 8.4 exp（-0.0084T摄氏度）; （2）在燃烧催化剂处产生二恶英/呋喃；（3）温度的微小变化会导致二恶英和呋喃异构体的同类物分布发生较大变化；
• Emission Factors and Importance of PCDD/Fs, PCBs, PCNs, PAHs and PM₁₀ from the Domestic Burning of Coal and Wood in the U.K.
  作者：Robert G. M. Lee、Peter Coleman、Joanne L. Jones、Kevin C. Jones、Rainer Lohmann

  DOI：10.1021/es048745i

  日期：2005.3.1

  fuels. However, their combined emissions from the domestic burning of coal and wood would contribute only a few percent to annual U.K. emission estimates. Emissions of PAHs and PM10 were major contributors to U.K. national emission inventories. Major emissions were found from the domestic burning for Cl1,2,3DFs, while the contribution of PCDD/F-sigmaTEQ to total U.K. emissions was minor.

  本文介绍了当煤和木材经过受控燃烧实验时针对一系列持久性有机污染物（POPs）得出的排放因子（EFs），旨在模拟空间供暖的家庭燃烧。排放了各种各样的持久性有机污染物，煤炭的排放量高于木材的排放量。对于颗粒物，PM10（大约10 g / kg燃料）和多环芳烃（对于sigmaPAHs大约100 mg / kg燃料）获得了最高的EF。对于氯化物，多氯联苯（PCB）的EF最高，而多氯萘（PCN），二苯并-对-二恶英（PCDD）和二苯并呋喃（PCDF）的丰度较低。对于sigmaPCB，EF大约为1000 ng / kg燃料，对于sigmaPCNs大约为100s ng / kg燃料，对于sigmaPCDD / Fs大约为100 ng / kg燃料。该研究证实，一氯化至三氯化二苯并呋喃Cl1,2,3DFs是低温燃烧过程（如煤炭和木材的国内燃烧）的有力指标。结论是，在固体燃料燃烧期间通常形成许多PCB和PC
• [EN] PFKFB3 INHIBITORS AND THEIR USES<br/>[FR] INHIBITEURS DE PFKFB3 ET LEURS UTILISATIONS
  申请人：GERO DISCOVERY LLC

  公开号：WO2020080979A1

  公开（公告）日：2020-04-23

  This disclosure relates to new phthalimide and isoindolinone derivatives and other PFKFB3 inhibitors for use in the treatment of diseases. The invention further relates to pharmaceutical compositions containing such PFKFB3 inhibitors, methods of preparation thereof, methods for their use as therapeutic agents, and methods of preparation of a medicament for use in therapy, as well as kits and other inventiions comprising such PFKFB3 inhibitors. These PFKFB3 inhibitors are useful for the treatment and prophylaxis of cancer, neurodegenerative diseases, autoimmune diseases, inflammatory disorders, multiple sclerosis, metabolic diseases, inhibition of angiogenesis and other diseases and conditions, where the modulation of PFKFB3 and/or PFKFB4 has beneficial effect as well as neuroprotection.

  这项披露涉及新的邻苯二甲酰亚胺和异吲哚酮衍生物以及其他PFKFB3抑制剂，用于治疗疾病。该发明还涉及含有此类PFKFB3抑制剂的药物组合物，其制备方法，作为治疗剂的使用方法，以及用于治疗的药物的制备方法，以及包含此类PFKFB3抑制剂的工具包和其他发明。这些PFKFB3抑制剂对于治疗和预防癌症、神经退行性疾病、自身免疫疾病、炎症性疾病、多发性硬化症、代谢性疾病、抑制血管生成以及其他疾病和情况具有用途，在这些情况下，PFKFB3和/或PFKFB4的调节具有益处，以及神经保护作用。