异补骨脂素 | 523-50-2

• 物质功能分类: 化学试剂 - 有机试剂 - 三环化合物
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 中文名称: 异补骨脂素
• 中文别名: 异补骨脂内酯；当归素；异补骨酯素；白芷素；爆裂霉素
• 英文名称: Angelicin
• 英文别名: furo[2,3-h]chromen-2-one
• CAS: 523-50-2
• 化学式: C₁₁H₆O₃
• mdl: MFCD00064930
• 分子量: 186.16
• InChiKey: XDROKJSWHURZGO-UHFFFAOYSA-N

物化性质

• 熔点：
  132-134°C
• 沸点：
  104°C/4mmHg(lit.)
• 密度：
  1.2477 (rough estimate)
• 溶解度：
  可溶于氯仿（少许）、乙酸乙酯（少许）、甲醇（少许）
• 最大波长(λmax)：
  302nm(EtOH)(lit.)
• LogP：
  2.080
• 物理描述：
  Solid
• 颜色/状态：
  White crystalline solid
• 气味：
  Slight hay-like odor
• 蒸汽压力：
  9.7X10-6 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Stable under recommended storage conditions.
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 保留指数：
  1774;1835

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 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：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

毒理性

• 毒性总结

识别和使用：异补骨脂素是一种天然呋喃香豆素。它已被测试为实验性治疗。人体研究：异补骨脂素在体外作为ERalpha受体激动剂，显著促进了MCF-7细胞增殖。当光激活时，当归素形成DNA单加合物。在人类细胞中，异补骨脂素促进了姐妹染色单体交换。动物研究：异补骨脂素在大鼠、小鼠和家兔中通过腹腔注射和口服给药时，具有强大的镇静、抗惊厥和中央肌肉松弛作用。异补骨脂素在细菌和动物细胞中具有光致突变性，生成DNA单加合物。

IDENTIFICATION AND USE: Isopsoralen is a natural furocoumarin. It has been tested as experimental therapy. HUMAN STUDIES: Isopsoralen acted in vitro as ERalpha receptor agonists and promoted MCF-7 cell proliferation significantly. Angelicin forms DNA monoadducts when photoactivated. In human cells isopsoralen promoted sister-chromatid exchanges. ANIMAL STUDIES: Isopsoralen had potent tranquilizing, anticonvulsant, and central muscle relaxant activity in rats, mice, and rabbits when given both ip and orally. Isopsoralen was photomutagenic in bacterial and animal cells generating DNA monoadducts.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

许多呋喃香豆素的作用机制是基于它们能够与DNA和其他细胞组分如RNA、蛋白质以及膜中的一些蛋白质（如磷脂酶A2和C、钙依赖性和cAMP依赖性蛋白激酶以及表皮生长因子）形成光加合物。呋喃香豆素插入DNA的碱基对之间，并在紫外线A照射后给出环加成物。

The mechanism of action many furocoumarins is based on their ability to form photoadducts with DNA and other cellular components such as RNA, proteins, and several proteins found in the membrane such as phospholipases A2 and C, Ca-dependent and cAMPdependent protein-kinase and epidermal growth factor. Furocoumarins intercalate between base pairs of DNA and after ultraviolet-A irradiation, giving cycloadducts. (L579)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌性证据

没有关于人类的数据。动物致癌性的证据有限。总体评估：第3组：该物质对人类致癌性无法分类。/天使ycin加紫外线A辐射/

No data are available in humans. Limited evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans. /Angelicin plus ultraviolet A radiation/

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剂：天使菌素加上紫外线A辐射

IARC Carcinogenic Agent:Angelicin plus ultraviolet A radiation

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：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

目标：研究不同浓度的补骨脂素和异补骨脂素的鼻腔吸收规律。方法：建立大鼠原位鼻腔循环实验模型，并通过高效液相色谱法测定补骨脂素和异补骨脂素的含量。结果：补骨脂素和异补骨脂素的鼻腔吸收符合零级动力学，随着浓度的增加而趋于饱和。结论：制备补骨脂素和异补骨脂素的鼻用制剂需要适宜的浓度。

OBJECTIVE: To investigate the nasal absorption regularities of psoralen and isopsoralen of different concentrations. METHOD: Building an experimental model of rat in situ nasal recirculation and determining the contents of psoralen and isopsoralen by HPLC. RESULT: The nasal absorption of psoralen and isopsoralen fitted in with zero order kinetics, getting saturated with the increase of concentration. CONCLUSION: A suitable concentration is necessary for the preparation of nasal remedies psoralen and isopsoralen.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

补骨脂中的香豆素组分是一种新药，其中补骨脂素和异补骨脂素是活性成分。通过液相色谱-串联质谱法研究了这两种化合物在大鼠静脉给药后的药代动力学、组织分布和排泄。补骨脂素和异补骨脂素的消除半衰期分别为4.88小时和5.35小时。给药后，组织曲线下面积以下列顺序降低：补骨脂素为肝>肺>心>肾>脾>脑；异补骨脂素为肾>肺>肝>心>脾>脑。给药后，补骨脂素和异补骨脂素分别有51.27%和56.25%以原型排泄，尿液是主要的排泄途径。此外，还研究了补骨脂素和异补骨脂素在大鼠口服给药后的药代动力学。补骨脂素和异补骨脂素的消除半衰期分别为4.13小时和5.56小时，它们的相对生物利用度分别为61.45%和70.35%。总的来说，结果表明补骨脂中的香豆素组分具有高的口服生物利用度，它们在静脉给药后能迅速广泛分布到组织中，但清除和排泄速度较慢。

Coumarin components from Psoralea corylifolia L. are novel drugs in which psoralen and isopsoralen are the active components. The pharmacokinetics, tissue distribution and excretion of the two compounds were studied by liquid chromatography-tandem mass spectrometry after intravenous administration to Wistar rats. The elimination half-lives of psoralen and isopsoralen were 4.88 and 5.35 hr. After dosing, the area under the curves of the tissues decreased in the following order: liver > lung > heart > kidney > spleen > brain for psoralen; and kidney > lung > liver > heart > spleen > brain for isopsoralen. After dosing, 51.27% of psoralen and 56.25% of isopsoralen were excreted as prototype, and urine was the major excretion route. In addition, the pharmacokinetics of psoralen and isopsoralen after oral administration to Wistar rats were also studied. The elimination half-lives of psoralen and isopsoralen were 4.13 and 5.56 hr, and their relative bioavailabilities were 61.45% and 70.35%. Overall, the results show that coumarin components from P. corylifolia L. have high oral bioavailability, they are rapidly and widely distributed into tissues after intravenous administration, but they are slowly cleared and excreted

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S26,S36/37/39
• 危险类别码：
  R40,R36/37/38,R20/21/22
• WGK Germany：
  3
• 海关编码：
  2932999099
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

简介

异补骨脂素是一种呋喃香豆素，通常从 P. corylifolia 的种子中分离出来。与其他呋喃香豆素一样，它对许多革兰氏 (+) 和革兰氏 (-) 细菌具有抗菌活性，并被证明可以防止他克林诱导的人肝来源 HepG2 细胞 (EC50 = 47 μg/ml) 中的细胞毒性和去氧肾上腺素预收缩的大鼠主动脉中的血管松弛。

毒性

异补骨脂素的LD50为322 mg/kg，对大鼠口服有急性毒性。可能的副作用包括改变昼夜节律和翻正反射、共济失调和镇痛。

生物活性

异补骨脂素 (Angelicin) 是一种天然的三环芳烃化合物，结构上与补骨脂素相似，具有抗癌、抗炎、抗病毒等活性。其IC50为49.56 μM；抑制MHV-68，IC50: 5.39 μg/ml (28.95 μM)。

化学性质

异补骨脂素是一种白色针状结晶，溶于氯仿，来源于补骨脂。

用途

异补骨脂素具有抗菌和消炎的作用，并且可用于含量测定、鉴定以及药理实验等。

反应信息

• 作为反应物：
  描述：

  异补骨脂素 生成 9-tritiofuro[2,3-h]chromen-2-one
  参考文献：
  名称：

  ISAACS, S. T.;RAPOPORT, H.;HEARST, J. E., J. LABELLED COMPOUNDS AND RADIOPHARM., 1982, 19, N 3, 345-356

  摘要：

  DOI：
• 作为产物：
  描述：

  (2H)-furo<2,3-h>-1-benzopyran 生成 异补骨脂素
  参考文献：
  名称：

  WULFF, WILLIAM D.;MCCALLUM, J. STUART;KUNNG, FEN-ANN, J. AMER: CHEM. SOC., 110,(1988) N2, C. 7419-7434

  摘要：

  DOI：

文献信息

• [EN] PI-3 KINASE INHIBITOR PRODRUGS<br/>[FR] PROMEDICAMENTS D'INHIBITEURS DE PI-3 KINASE
  申请人：SEMAFORE PHARMACEUTICALS INC

  公开号：WO2004089925A1

  公开（公告）日：2004-10-21

  The invention provides novel prodrugs of inhibitors of PI-3 kinase. The novel compounds are LY294002 and analogs thereof comprising a reversibly quaternized amine.

  这项发明提供了PI-3激酶抑制剂的新型前药。这些新型化合物是LY294002及其类似物，包括可逆性季铵化胺。
• [EN] THIENOPYRANONES AND FURANOPYRANONES AS KINASE, BROMODOMAIN, AND CHECKPOINT INHIBITORS<br/>[FR] THIÉNOPYRANONES ET FURANOPYRANONES EN TANT QU'INHIBITEURS DE KINASE, DE BROMODOMAINE ET DE POINTS DE CONTRÔLE
  申请人：SIGNALRX PHARMACEUTICALS INC

  公开号：WO2018140730A1

  公开（公告）日：2018-08-02

  The invention relates to compounds and methods of treating diseases including but not limited to, cancer, non-cancer proliferative disease, sepsis, autoimmune disease, viral infaction, atheroscleosis. Type 1 or 2 diabetes, obesity, inflammatory disease, or Myc-depenent disorder including by modulating biological processes by the inhibition of cell cycle checkpoint targets CDKs, and/or PI3 kinase, and/or bromodomain protein binding to substrates, comprising the administration of a compound(s) of Formula 1 -Vl (or pharmaceutically acceptable salts thereof) as defined herein.

  这项发明涉及化合物和治疗疾病的方法，包括但不限于癌症、非癌性增生性疾病、败血症、自身免疫疾病、病毒感染、动脉粥样硬化、1型或2型糖尿病、肥胖症、炎症性疾病或通过通过抑制细胞周期检查点靶点CDKs、和/或PI3激酶、和/或溴结构域蛋白结合到底物来调节生物过程，包括根据本文所定义的将化合物的给药作为公式1-Vl（或其药学上可接受的盐）的组成部分。
• Thienopyranones as Kinase and Epigenetic Inhibitors
  申请人：SignalRx Pharmaceuticals, Inc.

  公开号：US20150344494A1

  公开（公告）日：2015-12-03

  The invention relates to methods of treating diseases including but not limited to, cancer non-cancer proliferative disease, sepsis, autoimmune disease, viral infaction, atheroscleosis, Type 1 or 2 diabetes, obesity, inflammatory disease, or Myc-depenent disorder including by modulating biological processes by the inhibition of PI3 kinase and/or bromodomain protein binding to substrates composing the administration of a compound(s) of Formula I-IX (or pharmaceutically acceptable salts thereof) as defined herein.

  这项发明涉及治疗疾病的方法，包括但不限于癌症、非癌性增生性疾病、败血症、自身免疫疾病、病毒感染、动脉粥样硬化、1型或2型糖尿病、肥胖症、炎症性疾病或Myc依赖性疾病，通过调节生物过程，通过抑制PI3激酶和/或溴结构域蛋白与构成给药的底物结合的生物过程，包括使用本文所定义的化合物的给药（或其药学上可接受的盐）的I-IX式。
• Coumarins by Direct Annulation: β‐Borylacrylates as Ambiphilic C ₃ ‐Synthons
  作者：Max Wienhold、John J. Molloy、Constantin G. Daniliuc、Ryan Gilmour

  DOI：10.1002/anie.202012099

  日期：2021.1.11

  2‐halo‐phenol derivatives to generate structurally and electronically diverse coumarins. Key to this [3+3] disconnection is the BPin unit which serves a dual purpose as both a traceless linker for C(sp2)–C(sp2) coupling, and as a chromophore extension to enable inversion of the alkene geometry via selective energy transfer catalysis. Mild isomerisation is a pre‐condition to access 3‐substituted coumarins

  模块化β-硼基丙烯酸酯已被验证为可编程的、两亲性C 3 -合成子，可在2-卤代苯酚衍生物的级联成环中生成结构和电子多样化的香豆素。这种 [3+3] 断开的关键是 BPin 单元，它具有双重用途，既作为 C(sp 2 )–C(sp 2 ) 耦合的无痕连接子，又作为发色团延伸，通过选择性能量转移催化。轻度异构化是获得 3-取代香豆素的先决条件，并提供了分歧的手柄。该方法在含有这种古老化学型的代表性天然产物的合成中得到展示。公开了在 A 环上修饰的 π 扩展雌酮衍生物的简便进入，以证明该方法在生物测定开发或药物再利用中的潜力。
• REACTIVE CYANINE COMPOUNDS
  申请人：Corona Cesear

  公开号：US20110053162A1

  公开（公告）日：2011-03-03

  The invention provides compounds and compositions of Formulas I-VII, and methods of using the compounds. The compounds can be used to prepare dye conjugates that are uniformly and substantially more fluorescent on proteins, nucleic acids or other biopolymers, than conjugates labeled with structurally similar known carbocyanine dyes. In addition to having more intense fluorescence emission than structurally similar dyes at virtually identical wavelengths, and decreased artifacts in their absorption spectra upon conjugation to biopolymers, the compounds can have greater photostability and/or higher absorbance (extinction coefficients) at the wavelength(s) of peak absorbance than such structurally similar dyes.

  该发明提供了公式I-VII的化合物和组合物，以及使用这些化合物的方法。这些化合物可用于制备染料共轭物，其在蛋白质、核酸或其他生物聚合物上比使用结构类似已知碳氰染料标记的共轭物具有更均匀和明显更荧光。除了在几乎相同波长下比结构类似染料具有更强的荧光发射外，并且在与生物聚合物结合时吸收光谱中的伪迹减少，这些化合物在吸收峰波长处可能具有更高的光稳定性和/或更高的吸光度（消光系数）比这些结构类似的染料。

表征谱图