1,3-dihydroxy-6-methyl-9H-xanthen-9-one | 40547-32-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 1,3-dihydroxy-6-methyl-9H-xanthen-9-one
• 英文别名: 1,3-dihydroxy-6-methyl-9H-xanthone；6-methyl-1,3-dihydroxyxanthone；1,3-dihydroxy-6-methyl-xanthen-9-one；1,3-Dihydroxy-6-methyl-xanthen-9-on；1,3-dihydroxy-6-methylxanthen-9-one
• CAS: 40547-32-8
• 化学式: C₁₄H₁₀O₄
• mdl: MFCD11108885
• 分子量: 242.231
• InChiKey: USPLYEBEGSRMEJ-UHFFFAOYSA-N

物化性质

• 熔点：
  306 °C
• 沸点：
  498.1±45.0 °C(Predicted)
• 密度：
  1.452±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  1,3-dihydroxy-6-methyl-9H-xanthen-9-one 在 吡啶 、 4-二甲氨基吡啶 、 potassium osmate(VI) dihydrate 、 (8a,9R,8′′′a,9′′′R)-9,9′-[(2,5-diphenylpyrimidine-4,6-diyl)bis(oxy)]bis(6′-methoxy-10,11-dihydrocinchonan) 、 甲基磺酰胺 、 水 、 potassium carbonate 、 potassium hexacyanoferrate(III) 作用下， 以 二氯甲烷 、 丙酮 、 叔丁醇 为溶剂， 反应 7.0h， 生成 (1R,2R)-(-)-dicamphanoyl-3,3,10-trimethyl-6-methoxy-1,2-dihydropyrano[2,3-c]xanthen-7(1H)-one
  参考文献：
  名称：

  Anti-AIDS agents 85. Design, synthesis, and evaluation of 1R,2R-dicamphanoyl-3,3-dimethyldihydropyrano-[2,3-c]xanthen-7(1H)-one (DCX) derivatives as novel anti-HIV agents

  摘要：

  In this study, 1R,2R-dicamphanoyl-3,3-dimethydihydropyrano[2,3-c]xanthen-7(1H)-one (DCX) derivatives were designed and synthesized as novel anti-HIV agents against both wild-type and non-nucleoside reverse transcriptase (RT) inhibitor-resistant HIV-1 (RTMDR-1) strains. Twenty-four DCX analogs (6-29) were synthesized and evaluated against the non-drug-resistant HIV-1 NL4-3 strain, and selected analogs were also screened for their ability to inhibit the RTMDR-1 strain. Compared with the control 2-ethyl-3',4'-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (2-EDCP, 2), one of the best anti-HIV coumarin derivatives in our prior study, three DCX compounds (7, 12, and 22) showed better activity against both HIV strains with an EC50 range of 0.062-0.081 mu M, and five additional compounds (8, 11, 16, 18, and 21) exhibited comparable anti-HIV potency. Six DCX analogs (7, 11-12, 18, and 21-22) also showed enhanced selectivity index (SI) values in comparison to the control. Structure-activity relationship (SAR) information suggested that the extended conjugated system of the pyranoxanthone skeleton facilitates the interaction of the small DCX molecule within the viral binding pocket, consequently leading to enhanced anti-HIV activity and selectivity. Compared to DCP compounds, DCX analogs are a more promising new class of anti-HIV agents. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.025
• 作为产物：
  描述：

  4-甲基水杨酸 、 间苯二酚 在 zinc(II) chloride 、 三氯氧磷 作用下， 反应 3.0h， 以70.1%的产率得到1,3-dihydroxy-6-methyl-9H-xanthen-9-one
  参考文献：
  名称：

  一种Xanthone-NO供体化合物及其制备方法 和在制备抗肿瘤药物中的应用

  摘要：

  本发明属于抗肿瘤药物技术领域，公开了一种Xanthone‑NO供体化合物及其制备方法和在制备抗肿瘤药物中的应用。本发明的Xanthone‑NO供体化合物具有式Ⅰ所示的结构：其中，R1、R2、R3相同或不同的分别为H、OH、Cl、Br或F；n＝2～8。本发明制备方法为由取代水杨酸与间苯三酚制备xanthones，然后与1,n‑二溴取代烷反应制备3‑O‑溴代烷基xanthone，再溴转化得到。本发明化合物对乳腺癌、肝癌细胞具有优良的体外肿瘤细胞增殖抑制活性，并且能多靶点诱导肿瘤细胞的凋亡，因此可应用于制备抗肿瘤药物中，特别多靶点治疗癌症药物及由一氧化氮异常所引起肿瘤的药物。

  公开号：

  CN107602522B

文献信息

• Synthesis and bioactivity of novel xanthone and thioxanthone <scp>l</scp>-rhamnopyranosides
  作者：Gao-peng Song、Su-mei Li、Hong-zong Si、Yi-bin Li、Ya-sheng Li、Ji-hong Fan、Qian-qian Liang、Hui-bing He、Han-ming Ye、Zi-ning Cui

  DOI：10.1039/c5ra02846a

  日期：——

  A series of xanthone and thioxanthone rhamnopyranosides were designed and synthesized. Their in vitro cytotoxicity and topoisomerase inhibitory activity were evaluated. The bioassay results indicated that the introduction of the 2,3-di-O-acetyl-α-L-rhamnopyranosyl moiety to anthracene was helpful to improve the cytotoxicity in vitro. The modifications of anthracene had an important effect on the tumor

  设计并合成了一系列的an吨酮和噻吨酮鼠李吡喃糖苷。评价了它们的体外细胞毒性和拓扑异构酶抑制活性。生物测定结果表明，将2,3-二-O-乙酰基-α - L-鼠李糖基吡喃糖基部分引入蒽有助于改善体外细胞毒性。蒽的修饰对肿瘤细​​胞的生长抑制活性有重要影响。有趣的是，在这些蒽类似物中观察到了细胞毒性和topo I活性之间的一致性，这表明将聚亚甲基胺侧链或吡唑环并入蒽醌生色团能够同时增强topo I抑制活性和细胞毒性。其中，发现了作为新的先导化合物的化合物11，它对12种肿瘤细胞株具有广泛的体外细胞毒性，并具有潜在的抗多药耐药性。它证明了化合物11能诱导细胞凋亡的KB细胞通过内部和外部途径。流式细胞仪分析显示，用化合物11处理KB细胞会导致细胞凋亡，并伴随细胞周期停滞在G2 / M期。此外，化合物11引起拓扑异构酶I催化活性的显着且剂量依赖性的抑制。
• Incorporation of nitric oxide donor into 1,3-dioxyxanthones leads to synergistic anticancer activity
  作者：Jie Liu、Cao Zhang、Huailing Wang、Lei Zhang、Zhenlei Jiang、Jianrun Zhang、Zhijun Liu、Heru Chen

  DOI：10.1016/j.ejmech.2018.03.072

  日期：2018.5

  based on molecular similarity strategy. Incorporation of nitrate into 1,3-dioxyxanthones with electron-donating groups at 6–8 position brought about synergistic anticancer effect. Among them, compound 4g-4 was confirmed the most active agent against HepG-2 cells growth with an IC50 of 0.33 ± 0.06 μM. It dose-dependently increased intramolecular NO levels. This activity was attenuated by either NO scavenger

  五十1,3- dioxyxanthone硝酸盐（4A〜中，N = 1-6），设计并基于分子相似策略合成。将硝酸盐掺入1,3-二氧杂蒽酮中具有给电子基团的6-8位可产生协同的抗癌作用。其中，化合物4g-4被证实是最有效的抗HepG-2细胞生长的药物，IC 50为0.33±0.06μM。它剂量依赖性地增加了分子内NO水平。NO清除剂PTIO或线粒体醛脱氢酶（mtADH）抑制剂PCDA减弱了这种活性。凋亡分析表明，对于不同剂量的4g-4，早期/晚期凋亡和坏死对细胞死亡的不同贡献。4克-4在S期捕获更多的细胞。Western Blot的结果表明4g-4调节p53 / MDM2促进癌细胞凋亡。所有证据都支持4g-4是一种有前途的抗癌药。
• Identification of Xanthones as Selective Killers of Cancer Cells Overexpressing the ABC Transporter MRP1
  作者：Estelle Genoux-Bastide、Doriane Lorendeau、Edwige Nicolle、Samir Yahiaoui、Sandrine Magnard、Attilio Di Pietro、Hélène Baubichon-Cortay、Ahcène Boumendjel

  DOI：10.1002/cmdc.201100102

  日期：2011.8.1

  leading to cell death through apoptosis. However, clinical use of verapamil is hampered by its cardiotoxicity. Then, in the search for compounds that act similarly to verapamil, but without major side effects, we investigated xanthones. Herein we show that xanthones induce apoptosis among resistant cells overexpressing MRP1 similarly to the verapamil effect. Among the xanthones studied, 1,3‐dihydroxy‐6‐methoxyxanthone

  多药耐药蛋白1（MRP1）属于ATP结合盒（ABC）转运蛋白家族。MRP1通过与谷胱甘肽（GSH）结合或与游离GSH共同转运（在药物与GSH之间没有共价键合）引起药物外流，从而介导MDR（多药耐药性）。我们最近报道，钙通道阻滞剂维拉帕米可激活过表达MRP1的细胞中大量GSH外排，从而导致细胞通过凋亡而死亡。但是，维拉帕米的临床使用受到其心脏毒性的阻碍。然后，在寻找与维拉帕米具有相似作用但无主要副作用的化合物时，我们研究了氧杂蒽酮。在本文中，我们显示黄嘌呤类药物在过表达MRP1的耐药细胞中诱导细胞凋亡，这与维拉帕米的作用相似。在研究的氧杂蒽中，1 3-二羟基-6-甲氧基黄酮被认为是活性最高的衍生物，能够特异性杀灭被人MRP1转染的细胞，效力比维拉帕米还要强。在相同条件下，活性氧杂蒽酮对对照（敏感）细胞没有毒性作用。因此，黄嘌呤类被认为是选择性治疗MRP1阳性肿瘤的新型潜在抗癌药。
• 呫吨酮类化合物及其抗抑郁用途
  申请人：南京工业大学

  公开号：CN104177324B

  公开（公告）日：2016-05-11

  本发明公开了一种呫吨酮类化合物及其抗抑郁用途，化合物为具有式（I）结构或其药学上可接受的盐。该类化合物经实验表明，具有良好的抗抑郁活性，其中部分化合物的抗抑郁活性优于文拉法辛，因此本发明的化合物及其药用盐可以用于制备抗抑郁药物。
• (2-Arylhydrazonomethyl)-substituted xanthones as antimycotics: synthesis and fungistatic activity against Candida species
  作者：Stéphane Moreau、Martine Varache-Lembège、Stéphane Larrouture、Djibril Fall、Arlette Neveu、Gérard Deffieux、Joseph Vercauteren、Alain Nuhrich

  DOI：10.1016/s0223-5234(01)01332-0

  日期：2002.3

  A series of arylhydrazones derived from various 6,8-diacetoxy- or 6,8-dihydroxy-9-oxo-9H-xanthene carboxaldehydes were synthesized and evaluated for their in vitro antifungal properties against two human pathogenic yeasts (Candida albicans and C. krusei) according to a diffusion method. The activity was strongly dependent from the position of the (1-arylhydrazinyl-2-ylidene)methyl chain in the xanthone molecular skeleton. Compounds having the nitrogen side chain in the 4-position, with a further halogen substitution on the terminal phenyl ring showed fungistatic effects. Within this series, the 4-fluorophenylhydrazinyl derivative 13g exhibited the highest activity, particularly against C. krusei, with a greater efficacy than that of econazole, used as reference. (C) 2002 Published by Editions scientifiques et medicales Elsevier SAS.