claulansine F | 1361526-60-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: claulansine F
• 英文别名: 8-methoxy-3,3-dimethyl-11H-pyrano[3,2-a]carbazole-5-carbaldehyde
• CAS: 1361526-60-4
• 化学式: C₁₉H₁₇NO₃
• 分子量: 307.349
• InChiKey: QBWFLAHUWCLAKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  claulansine F 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以87%的产率得到8-methoxy-3,3-dimethyl-3H,11H-pyrano[3,2-a]carbazole-5-methanol
  参考文献：
  名称：

  一类吡喃并咔唑生物碱及其制备方法和其药物组合物与用途

  摘要：

  本发明公开了一类吡喃并咔唑生物碱及其制备方法和其药物组合物与用途。具体而言，本发明公开了如通式I所示的吡喃[3,2‑a]咔唑生物碱。这类生物碱是通过人工合成的方式制备，含有其药物组合物，以及它们在制备治疗神经退行性疾病药物中的应用，特别是脑卒中或阿尔茨海默病、抑郁症、帕金森病。

  公开号：

  CN108239095A
• 作为产物：
  描述：

  3-tert-butyldiphenylsilyloxy-4-methylnitrobenzene 在 titanium(IV) isopropylate 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 氢气 、 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 溶剂黄146 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 反应 97.5h， 生成 claulansine F
  参考文献：
  名称：

  Pyrano[3,2-a]carbazole alkaloids as effective agents against ischemic stroke in vitro and in vivo

  摘要：

  A series of pyrano[3,2-a]carbazole alkaloids were designed and synthesized as analogues of Claulansine F (Clau F, 10a) isolated from Clausena lansium. Some of compounds showed strong neuroprotective effects and were promising agents against ischemic stroke. Among these compounds, 7c was the most active in inhibiting the programmed death of PC12 cells and primary cortical neurons. This compound induced neuroprotection following ischemic reperfusion and decreased neurological deficit scores in treated animals. Furthermore, 7c could penetrate the blood-brain barrier (BBB) in rats, and its exposure in the brain was 4.3-fold higher than that in plasma. More importantly, compared to edaravone, 7c exhibited stronger free radical scavenging activity. Our findings suggest that 7c may be promising for further evaluation as an intervention for ischemic stroke. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.11.084

文献信息

• Claulansine F–Donepezil Hybrids as Anti-Alzheimer’s Disease Agents with Cholinergic, Free-Radical Scavenging, and Neuroprotective Activities
  作者：Yingda Zang、Ke Liu、Weiping Wang、Chuangjun Li、Jie Ma、Jingzhi Yang、Xinyi Chen、Xiaoliang Wang、Dongming Zhang

  DOI：10.3390/molecules26051303

  日期：——

  The multifactorial nature of Alzheimer’s disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F–donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC50) 1.63–4.62 μM). Moreover, (E)-3-(8-(tert-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol-5-yl)-N-((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide (6bd) exhibited better neuroprotective effects against OGD/R (oxygen–glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, 6bd could cross the blood–brain barrier in vitro. More importantly, compared to edaravone, 6bd had stronger free-radical scavenging activity. Molecular docking studies revealed that 6bd could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate 6bd as a leading structure worthy of further investigation.

  阿尔茨海默病（AD）的多因素性质需要开发多靶点药物，以应对关键的病理过程。总共设计和合成了26种Claulansine F-donepezil杂合物作为多靶点药物。在这些化合物中，有六种表现出优秀的乙酰胆碱酯酶（AChE）抑制活性（半最大抑制浓度（IC50）为1.63-4.62μM）。此外，（E）-3-（8-（叔丁基）-3,3-二甲基-3,11-二氢吡喃[3,2-a]咔唑-5-基）-N-（（1-（2-氯苯甲基）哌啶-4-基）甲基）丙烯酰胺（6bd）对OGD/R（氧-葡萄糖剥夺/再氧化）表现出比Claulansine F更好的神经保护作用。此外，6bd在体外可以穿越血脑屏障。更重要的是，与雷达伏酮相比，6bd具有更强的自由基清除活性。分子对接研究揭示了6bd可以与AChE的催化活性位点相互作用。所有这些出色的体外结果表明6bd作为一个值得进一步研究的领先结构。
• Design, synthesis and biological evaluation of pyranocarbazole derivatives against Alzheimer’s disease, with antioxidant, neuroprotective and cognition enhancing properties
  作者：Yingda Zang、Jingwen Ning、Ke Liu、Meiyu Shang、Caixia Zang、Chuangjun Li、Jie Ma、Xinyi Chen、Jingwei Ma、Gen Li、Yang Yang、Xiuqi Bao、Dan Zhang、Dongming Zhang

  DOI：10.1016/j.bioorg.2022.106179

  日期：2022.12

  and synthesized as derivatives of Claulansine F and CZ-7. Some of the compounds showed strong neuroprotective effects and anti-lipid peroxidation capacity. Among these compounds, 10b, introduced leucine at the C-3 position of pyranocarbazole, was the most active in inhibiting the programmed death of SH-SY5Y cells. This compound exhibited stronger free radical scavenging activity than Edaravone. Furthermore

  设计并合成了一系列新型吡喃并咔唑生物碱，作为 Claulansine F 和 CZ-7 的衍生物。一些化合物显示出很强的神经保护作用和抗脂质过氧化能力。在这些化合物中，在吡喃并咔唑的C-3位引入亮氨酸的10b对SH-SY5Y细胞程序性死亡的抑制作用最强。该化合物表现出比依达拉奉更强的自由基清除活性。此外，10b可以穿透血脑屏障 (BBB)。更重要的是，10b在 10-40 mg/kg 的剂量范围内表现出学习和记忆改善的趋势。机制研究表明，10b可降低Aβ脑内氧化应激25-35 -中毒小鼠，进而改善Aβ 25-35 -中毒小鼠的认知功能。我们的研究结果表明，10b可能有望作为阿尔茨海默氏病的干预措施进行进一步评估。
• 一类吡喃并咔唑生物碱衍生物及其治疗阿尔茨海默症的用途
  申请人：中国医学科学院药物研究所

  公开号：CN114685519A

  公开（公告）日：2022-07-01

  本发明涉及天然药物及药物化学领域，公开了一类吡喃并咔唑生物碱衍生物及其治疗阿尔茨海默症的用途。具体而言，本发明公开了如通式I、II所示的一类含苄基哌嗪片段的吡喃[3,2‑a]咔唑生物碱。这类化合物是通过人工合成的方式制备，含有其药物组合物，以及它们在制备治疗阿尔茨海默症的药物用途。
• Pyranocarbazole derivatives as potent anti-cancer agents triggering tubulin polymerization stabilization induced activation of caspase-dependent apoptosis and downregulation of Akt/mTOR in breast cancer cells
  作者：Om P.S. Patel、Ashutosh Arun、Pankaj K. Singh、Deepika Saini、Sharanbasappa Shrimant Karade、Manish K. Chourasia、Rituraj Konwar、Prem P. Yadav

  DOI：10.1016/j.ejmech.2019.02.003

  日期：2019.4

  A series of new pyranocarbazole derivatives were synthesized via semi-synthetic modification of koenimbine (la) and koenidine (1b) isolated from the leaves of Murraya koenigii. Among all, compound 3bg displayed significant anti-cancer activity against MDA-MB-231, DU145 and PC3 cell lines with the IC50 values of 3.8, 7.6 and 5.8 mu M, respectively. It was also observed that the halogenated-benzyl substitution at N-9 position, C-3 Methyl and C-7 methoxy group on carbazole motif are favoured for anti-cancer activity. The detailed investigation was carried out with compound 3bg and its SEDDS (self-emulsifying drug delivery systems) formulation 3bgF. The in vivo drug release behavior study showed that the formulation enhanced slow release and better bioavailability at a tumor site. Compound 3bg and its formulation (3bgF) significantly inhibited cell proliferation and colony formation, induced G2/M arrest, reduced cellular ROS generation and induced caspase-dependent apoptosis in MDA-MB-231 cells. 3bg also induced significant alteration of Bax/Bcl expression ratio suggesting involvement of mitochondrial apoptosis. Additionally, 3bg caused down-regulation of mTOR/Akt survival pathway. 3bg do not bind to DNA, but interacts with tubulin as observed with in silico molecular docking studies. This interaction results in stabilization of tubulin polymerization similar to paclitaxel as detected in cell-free assay. Oral administration of 3bgF for 30 days at dose rate of 10 and 20 mg/kg body weight significantly reduced tumor growth in syngenic rat LA-7 mammary tumor model. These results indicated that the pyranocarbazole natural product based N-substituted analogues can act as potential anti-cancer lead. (C) 2019 Elsevier Masson SAS. All rights reserved.