(6aR)-2-methoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-1-ol | 37082-15-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: (6aR)-2-methoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-1-ol
• 英文别名: (-)-lirinidine；Nuciferine；lirinidine；1-hydroxy-2-methoxyaporphine
• CAS: 37082-15-8
• 化学式: C₁₈H₁₉NO₂
• 分子量: 281.354
• InChiKey: YXVXMURDCBMPRH-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6aR)-2-methoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-1-ol 在 aluminum tri-bromide 作用下， 以 乙腈 为溶剂， 反应 48.0h， 以65%的产率得到(6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-1,2-diol
  参考文献：
  名称：

  Synthesis and structure–activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors

  摘要：

  Acetylcholinesterase inhibitors (AChEIs) are currently the best available pharmacotherapy for Alzheimer patients, but because of bioavailability issues, there is still great interest in discovering better AChEIs. The aporphine alkaloid is an important class of natural products, which shows diverse biological activity, such as acetylcholinesterase inhibitory activity. To find new lead AChEIs compounds, eight aporphine alkaloids were synthesized by O-dealkylation, N-dealkylation, and ring aromatization reactions using nuciferine as raw material. The anti-acetylcholinesterase activity of synthesized compounds was measured using modified Ellman's method. The results showed that some synthesized compounds exhibited higher affinity to AChE than the parent compound nuciferine. Among these compounds, 1,2-dihydroxyaporphine (2) and dehydronuciferine (5) were the most active compounds (IC50 = 28 and 25 mu g/mL, respectively). Preliminary analysis of structure-activity relationships suggested that aromatization of the C ring, the presence of the alkoxyl group at C1 and the hydroxy group at C2 position as well as the alkyl substituent at the N atom were favorable to the acetylcholinesterase inhibition. Molecular docking was also applied to predict the binding modes of compounds 1, 2, and 9 into the huperzine A binding site of AChE.

  DOI：

  10.1007/s00044-013-0905-9
• 作为产物：
  描述：

  荷叶碱 在 sodium tetrahydroborate 、 二苄基二硒醚 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以76%的产率得到(6aR)-2-methoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-1-ol
  参考文献：
  名称：

  Synthesis and structure–activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors

  摘要：

  Acetylcholinesterase inhibitors (AChEIs) are currently the best available pharmacotherapy for Alzheimer patients, but because of bioavailability issues, there is still great interest in discovering better AChEIs. The aporphine alkaloid is an important class of natural products, which shows diverse biological activity, such as acetylcholinesterase inhibitory activity. To find new lead AChEIs compounds, eight aporphine alkaloids were synthesized by O-dealkylation, N-dealkylation, and ring aromatization reactions using nuciferine as raw material. The anti-acetylcholinesterase activity of synthesized compounds was measured using modified Ellman's method. The results showed that some synthesized compounds exhibited higher affinity to AChE than the parent compound nuciferine. Among these compounds, 1,2-dihydroxyaporphine (2) and dehydronuciferine (5) were the most active compounds (IC50 = 28 and 25 mu g/mL, respectively). Preliminary analysis of structure-activity relationships suggested that aromatization of the C ring, the presence of the alkoxyl group at C1 and the hydroxy group at C2 position as well as the alkyl substituent at the N atom were favorable to the acetylcholinesterase inhibition. Molecular docking was also applied to predict the binding modes of compounds 1, 2, and 9 into the huperzine A binding site of AChE.

  DOI：

  10.1007/s00044-013-0905-9

文献信息

• [EN] R(-)-2-METHOXY-11-HYDROXYAPORPHINE AND DERIVATIVES THEREOF<br/>[FR] R(-)-2-MÉTHOXY-11-HYDROXYAPORPHINE ET SES DÉRIVÉS
  申请人：MCLEAN HOSPITAL CORP

  公开号：WO2009009083A1

  公开（公告）日：2009-01-15

  The invention features derivatives of R(-)-2-methoxy-l 1- hydroxyaporphines and methods of treating Parkinson's disease, sexual dysfunction, and depressive disorders therewith.

  本发明涉及R(-)-2-甲氧基-11-羟基阿波啡的衍生物及其用于治疗帕金森病、性功能障碍和抑郁障碍的方法。
• 荷叶碱衍生物及其制备方法和应用
  申请人：山东师范大学

  公开号：CN114516837A

  公开（公告）日：2022-05-20

  本发明涉及医药领域，具体涉及一种荷叶碱衍生物及其制备方法和应用。本发明所述荷叶碱衍生物具有式(I)所示结构：其中，R为取代苄基或取代吡啶基；所述取代苄基是被选自卤素、烷基、烷氧基、卤代烷基、硝基、氰基中的一种或多种取代基所取代的；所述取代吡啶基是被选自烷基所取代的；该结构式化合物与有机酸或无机酸形成的盐。该类化合物因具有生物碱与含杂原子的芳烃结构特征，可作为α‑糖苷酶抑制剂和/或胆汁酸螯合剂，具有良好的降糖降脂活性，可用于治疗与改善高血糖或高血脂等症的应用。
• 荷叶碱衍生物及其在制备降尿酸药物中的应用
  申请人：浙江沙棘生物科技有限公司

  公开号：CN114558012B

  公开（公告）日：2023-09-01

  本申请提供一种荷叶碱衍生物及其在制备降尿酸药物中的应用。其中，荷叶碱衍生物具有式I所示结构，其具有抑制URAT1表达的活性，可作为URAT1抑制剂用于降尿酸。式I其中，R选自烷基、环烷基、芳烃基、杂环基；所述烷基、芳烃基和杂环基是未被取代的或者被选自烷基、烷氧基、卤素、氰基、硝基中的一个或多个取代基所取代的；其中，所述芳烃基选自苯基、苄基、萘基和联二苯基；所述杂环基选自噻吩基、吡啶基、喹啉基、异喹啉基和异噁唑；所述烷基为C1‑C8烷基，所述环烷基为C3‑C6环烷基；所述药学上可接受的盐为式I化合物的无机酸盐或有机酸盐；其中，R不为溴甲基、异丙基、正己烷基、正辛烷基。
• Synthesis and structure–activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors
  作者：Zhongduo Yang、Zhuwen Song、Weiwei Xue、Jie Sheng、Zongmei Shu、Yin Shi、Jibei Liang、Xiaojun Yao

  DOI：10.1007/s00044-013-0905-9

  日期：2014.6

  Acetylcholinesterase inhibitors (AChEIs) are currently the best available pharmacotherapy for Alzheimer patients, but because of bioavailability issues, there is still great interest in discovering better AChEIs. The aporphine alkaloid is an important class of natural products, which shows diverse biological activity, such as acetylcholinesterase inhibitory activity. To find new lead AChEIs compounds, eight aporphine alkaloids were synthesized by O-dealkylation, N-dealkylation, and ring aromatization reactions using nuciferine as raw material. The anti-acetylcholinesterase activity of synthesized compounds was measured using modified Ellman's method. The results showed that some synthesized compounds exhibited higher affinity to AChE than the parent compound nuciferine. Among these compounds, 1,2-dihydroxyaporphine (2) and dehydronuciferine (5) were the most active compounds (IC50 = 28 and 25 mu g/mL, respectively). Preliminary analysis of structure-activity relationships suggested that aromatization of the C ring, the presence of the alkoxyl group at C1 and the hydroxy group at C2 position as well as the alkyl substituent at the N atom were favorable to the acetylcholinesterase inhibition. Molecular docking was also applied to predict the binding modes of compounds 1, 2, and 9 into the huperzine A binding site of AChE.
• Synthesis and bioactivity evaluation of novel nuciferine derivatives with antihyperuricemia and nephroprotective effects
  作者：Yu-kai Zhang、Jia-shu Chen、Min-min Wang、Chuan-zeng Wang、Mu-xuan Wang、Zhen Wang、Qin-liang Yang、Bin Sun、Jin-yue Sun、Yu-fa Liu、Chao Liu

  DOI：10.1016/j.bioorg.2022.105916

  日期：2022.9