隐丹参酮 | 35825-57-1

• 物质功能分类: 生物化工 - 天然产物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 隐丹参酮
• 中文别名: 隐丹参醌
• 英文名称: Cryptotanshinone
• 英文别名: CTS；(1R)-1,6,6-trimethyl-2,7,8,9-tetrahydro-1H-naphtho[1,2-g][1]benzofuran-10,11-dione；CPT；crytotanshinone
• CAS: 35825-57-1
• 化学式: C₁₉H₂₀O₃
• 分子量: 296.366
• InChiKey: GVKKJJOMQCNPGB-JTQLQIEISA-N

物化性质

• 熔点：
  192°C(lit.)
• 沸点：
  459.0±45.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：≥5mg/mL
• 最大波长(λmax)：
  263nm(lit.)
• LogP：
  4.130 (est)
• 碰撞截面：
  168 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  6.1
• 危险品标志：
  N,T
• 安全说明：
  S45,S60,S61
• 危险类别码：
  R50/53,R25
• WGK Germany：
  3
• 海关编码：
  2932999099
• 危险品运输编号：
  UN2811 - class 6.1 - PG 3 - EHS - Toxic solids, organic, n.o.s., HI： all
• RTECS号：
  SF8282645
• 包装等级：
  III
• 危险类别：
  6.1
• 危险标志：
  GHS06,GHS09
• 危险性描述：
  H301,H410
• 危险性防范说明：
  P273,P301 + P310,P501

制备方法与用途

根据提供的信息，以下是对隐丹参酮的概述：

化学性质与来源

• 化学性质：隐丹参酮是一种易溶于甲醇、乙醇、苯和乙醚的二萜类化合物。它特别容易溶解在丙酮和氯仿中。
• 来源：来源于唇形科植物丹参。

制剂研究

1. 脂质体：

   • 采用超声-匀浆-冷冻干燥法制备隐丹参酮纳米脂质体。
   • 冷冻干燥法制备的粒径范围为20至80nm之间，随着大豆卵磷脂与隐丹参酮配比的减小，粒径逐渐减少，包封率也相应降低。
   • 体外释药表现为零级动力学释药特征。

2. 固体分散体：

   • 使用溶剂蒸发法制备隐丹参酮-PVP固体分散体。
   • 熔融法制备隐丹参酮-PEG固体分散体。
   • 实验结果显示，PVP固体分散体在45分钟内的溶出度是原料药的9.7倍，而PEG固体分散体为7.5倍。PVP固体分散体比PEG固体分散体具有更高的溶出度。

体内代谢

• 代谢途径：大鼠口服隐丹参酮后3小时内，在胆汁中首先检测到原形药物和丹参酮Ⅱ-A。
• 具体代谢物：
  • 在6小时后的胆汁中出现的羟基化产物，例如1,2,3,4及5号化合物。这表明肝脏中的药酶发挥了作用。
  • 某些代谢产物在体外试验中表现出抑菌活性，但以原形药物(6号)的活性最强。

用途与药理

• 用途：隐丹参酮用于含量测定、鉴定和药理实验等场合。
• 药理作用：
  • 具有抗氧化、抗衰老功能；
  • 对治疗冠心病、心绞痛和心肌损害有一定疗效；
  • 拥有抑菌活性，1mg/ml浓度可抑制金黄色葡萄球菌及绿脓杆菌的生长。

结论

隐丹参酮是一种重要的天然产物，在药物制剂研究中展现出良好的溶出度提高潜力，并在生物体内通过复杂的代谢途径进行转化。了解其化学性质、药理作用及其代谢过程有助于更好地开发和应用这类化合物于临床治疗领域。

反应信息

• 作为反应物：
  描述：

  隐丹参酮 在 碳酸氢钠 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以20%的产率得到cryptotanshinone anhydride
  参考文献：
  名称：

  Potent, Irreversible Inhibition of Human Carboxylesterases by Tanshinone Anhydrides Isolated fromSalvia miltiorrhiza(“Danshen”)

  摘要：

  The roots of Salvia miltiorrhiza ("Danshen") have been used in Chinese herbal medicine for centuries for a host of different conditions. While the exact nature of the active components of this material are unknown, large amounts of tanshinones are present in extracts derived from these samples. Recently, the tanshinones have been demonstrated to be potent human carboxylesterase (CE) inhibitors, with the ability to modulate the biological activity of esterified drugs. During the course of these studies, we also identified more active, irreversible inhibitors of these enzymes. We have purified, identified, and synthesized these molecules and confirmed them to be the anhydride derivatives of the tanshinones. These compounds are exceptionally potent inhibitors (K-i < 1 nM) and can inactivate human CEs both in vitro and in cell culture systems and can modulate the metabolism of the esterified drug oseltamivir. Therefore, the coadministration of Danshen extracts with drugs that contain the ester chemotype should be minimized since, not only is transient inhibition of CEs observed with the tanshinones, but also prolonged irreversible inhibition arises via interaction with the anhydrides.

  DOI：

  10.1021/acs.jnatprod.8b00378
• 作为产物：
  描述：

  3-((S)-1-((tert-butyldimethylsilyl)oxy)-2-propyl)-7,7-dimethyl-4-hydroxy-2-((triisopropylsilyl)oxy)-7,8,9,10-tetrahydrophenanthrene 在 硫酸 、 四丁基氟化铵 、 氧气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 40.75h， 生成 隐丹参酮
  参考文献：
  名称：

  Aromatic Annulation Strategy for the Synthesis of Angularly-Fused Diterpenoid Quinones. Total Synthesis of (+)-Neocryptotanshinone, (-)-Cryptotanshinone, Tanshinone IIA, and (.+-.)-Royleanone

  摘要：

  The application of a photochemical aromatic annulation strategy in highly efficient total syntheses of several diterpenoid quinones isolated from the traditional Chinese medicine Dan Shen is reported. The pivotal step in each synthesis involves the assembly of a key tricyclic intermediate via the application of a recently developed ''second-generation'' photochemical aromatic annulation method for the construction of highly substituted aromatic systems. In the total synthesis of neocrypto-tanshinone,;the synthesis of the requisite diazo ketone annulation substrate 7 was achieved using palladium-mediated coupling reactions and an intramolecular Friedel-Crafts cyclization to form key carbon-carbon bonds. The pivotal aromatic annulation reaction was then accomplished by irradiating a solution of the diazo ketone 7 and the readily available siloxyalkyne 6 in benzene at room temperature. The desired tricyclic phenol 16 was produced in 58-65% yield and was then converted to (+)-neocryptotanshinone (1) by treatment with tetra-n-butylammonium fluoride in the presence of oxygen. Cyclization to generate (-)-cryptotanshinone (2) was accomplished in high yield by brief exposure of 1 to an ethanolic solution of concentrated sulfuric acid, and dehydrogenation of 2 with DDQ furnished tanshinone IIA (3). As a further demonstration of the utility of the photochemical aromatic annulation strategy in the construction of angularly-fused diterpenes, the total synthesis of(+/-)-royleanone (4) was also investigated. Irradiation of a solution of the diazo ketone 18 and siloxyalkyne 25 produced the tricyclic intermediate 26, which was converted in two steps to royleanone by desilylation and oxidation.

  DOI：

  10.1021/jo00131a006

文献信息

• Design, synthesis and cytotoxicity of nitrogen-containing tanshinone derivatives
  作者：Ming-Ming Li、Fan Xia、Cheng-Ji Li、Gang Xu、Hong-Bo Qin

  DOI：10.1016/j.tetlet.2017.11.046

  日期：2018.1

  synthesize a small library of nitrogen heterocyclic derivatives featured with oxazole, imidazole, and pyrazine ring between C-11/C-12 by simple methods. Except for salviamine A and isosalviamine A, 22 new derivatives were synthesized. Their structures were confirmed by spectroscopic analysis. Moreover, 11 derivatives exhibited moderate cytotoxic activities against five human cancer lines in vitro.

  丹参酮用作起始原料，可通过简单方法合成C-11 / C-12之间以恶唑，咪唑和吡嗪环为特征的小氮杂环衍生物库。除了唾液胺A和异水杨胺A以外，还合成了22种新的衍生物。通过光谱分析证实了它们的结构。此外，有11种衍生物在体外对5种人类癌症系表现出中等的细胞毒活性。
• CHEMICALLY ACTIVATED WATER-SOLUBLE PRODRUG
  申请人：SUMITOMO DAINIPPON PHARMA CO., LTD

  公开号：US20200207782A1

  公开（公告）日：2020-07-02

  The present invention addresses the problem of providing a novel chemically activated water-soluble prodrug. The present invention provides a compound represented by formula (1), or a pharmacologically acceptable salt thereof (in the formula, A represents A-0; X 1 and X 2 are the same as or different from each other and each independently represent a hydroxyl group or —O—C(═O)—Y—(C(R 1A ) (R 1B ))n-NH—R 2 , where X 1 and X 2 are not simultaneously hydroxyl groups, n is 2, 3, or 4, Y represents an oxygen atom or —NR 4 , R 1A and R 1B are the same as or different from each other and each independently represent a hydrogen atom, etc., and R 2 represents a hydrogen atom, etc.; and R a to R d are optionally present, are the same as or different from each other, and each independently represent a hydrogen atom, etc.).

  本发明解决了提供一种新型化学活化的水溶性前药的问题。本发明提供了由式（1）表示的化合物，或其药理学上可接受的盐（在该式中，A代表A-0；X1和X2彼此相同或不同，每个独立地代表一个羟基或—O—C(═O)—Y—(C(R1A)(R1B))n-NH—R2，其中X1和X2不同时是羟基，n为2、3或4，Y代表氧原子或—NR4，R1A和R1B彼此相同或不同，每个独立地代表氢原子等，R2代表氢原子等；以及Ra到Rd可选地存在，彼此相同或不同，每个独立地代表氢原子等）。
• [EN] NOVEL PHENAZINE DERIVATIVES AND THEIR USE<br/>[FR] NOUVEAUX DÉRIVÉS DE PHÉNAZINE ET LEUR UTILISATION
  申请人：UNIV CATHOLIQUE LOUVAIN

  公开号：WO2012085222A1

  公开（公告）日：2012-06-28

  The present invention is directed to novel compounds of formula (I) and their use as anti-angiogenic agents and anti-cancer agents.

  本发明涉及式（I）的新化合物及其作为抗血管生成和抗癌剂的用途。
• AMYLOID-BINDING COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Vanderbilt University

  公开号：US20210011008A1

  公开（公告）日：2021-01-14

  A method of screening for amyloid-binding compounds, amyloid-binding compounds, and a method of detecting amyloid-β (Abeta) plaques in a subject are disclosed. The method of screening for amyloid-binding compounds includes combining amyloid, a dye, and at least one test compound to form a sample solution; equilibrating the sample solution; measuring a fluorescence signal of the sample solution; and comparing the measured fluorescence signal of the sample to a control; wherein attenuation of the fluorescence signal, as compared to the control, indicates that one or more of the test compounds bind amyloid. The amyloid-binding compound includes a compound detected by the screening method. The method of detecting amyloid-β (Abeta) plaques in a subject includes administering one or more of the amyloid-binding compounds to the subject, and detecting the compound within the subject.

  揭示了一种筛选淀粉样结合化合物、淀粉样结合化合物的方法，以及检测受试者中淀粉-β（Abeta）斑块的方法。筛选淀粉样结合化合物的方法包括将淀粉、染料和至少一种试剂化合物组合以形成样品溶液；平衡样品溶液；测量样品溶液的荧光信号；并将所测得的样品的荧光信号与控制进行比较；其中，与控制相比减弱的荧光信号表明一个或多个试剂化合物与淀粉结合。淀粉样结合化合物包括通过筛选方法检测到的化合物。在受试者中检测淀粉-β（Abeta）斑块的方法包括向受试者施用一个或多个淀粉样结合化合物，并在受试者内检测化合物。
• 一种具C环骈合内酯环新颖骨架的松香烷类 化合物及其制备方法与应用
  申请人：杭州济蒿医药科技有限公司

  公开号：CN111606917B

  公开（公告）日：2021-10-01

  本发明公开了一种具C环骈合内酯环新颖骨架的松香烷类化合物，以松香烷二萜醌类化合物为原料，在金属催化剂的作用下，通过与酸酐缩合得到具有C环骈合内酯环新颖骨架的松香烷类化合物。本发明构建的一类新的松香烷类化合物，有效改进了化合物的非平面性，不仅在结构上具有新颖性，而且相应的生物活性也得到显著提升，提示该类化合物具有更大的成药潜力。

表征谱图