tetrahydroberberine hydrochloride | 19976-45-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 原小檗碱生物碱及其衍生物
• 英文名称: tetrahydroberberine hydrochloride
• 英文别名: (+/-)-Canadine HCl；16,17-dimethoxy-5,7-dioxa-13-azapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-2,4(8),9,15(20),16,18-hexaene;hydrochloride
• CAS: 19976-45-5
• 化学式: C₂₀H₂₁NO₄*ClH
• 分子量: 375.852
• InChiKey: LQVZRJHGNBMZAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  40.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tetrahydroberberine hydrochloride 在 碘 、 sodium acetate 、 三溴化硼 、 溶剂黄146 、 cesium fluoride 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 coptisine iodide
  参考文献：
  名称：

  Cytotoxicity evaluation of natural coptisine and synthesis of coptisine from berberine

  摘要：

  The crude extract (80% MeOH in water) of Chelidonii herba exhibited very interesting cytotoxicity against brine shrimp (Artemia salina Leach) nauplii and cultured human tumour cell in vitro, the colon carcinoma HT 29 (144 h treatment). Fractionation of the crude extract and bioassay-guided procedures showed that the cytotoxic and,the antitumour activities. were concentrated in the basic extract. On the basis of IR, MS and H-1 NMR the compound responsible of the cytotoxic activity was determined to be coptisine. Cytotoxicity evaluation of-coptisine was next extended to-a panel of human and murine cell lines in comparison with the established antitumour drugs mitoxantrone, doxorubicin (D. x) and cisplatin. (CDDP). Coptisine was cytotoxic on LoVo and HT 29 and less potent on L-1210, and it was partially crossresistant on the human tumour colon cell line resistant to Dx, LoVo/Dx, whereas it was not significantly crossresistant on the murine leukaemia cell line resistant to. CD. DP, L-1210/CDDP. Coptisine alkaloid was then synthesised in gram amount from commercial berberine. A four-step synthetic route was elaborated. The overall yield was about 8-10%. The structural identity of synthetic coptisine was verified by IR and NMR methods. A comparison of the cytotoxic effects on the human tumour colon cell line LoVo and on the murine leukaemia L1210 showed, for both natural and synthetic coptisines, a comparable cytotoxic activity more evident against-HT 29 cell line and LoVo. cell line, while the activity was lower against the L1210 cell line. (C) 2001 Editions scientifiques et medicales. Elsevier SAS.

  DOI：

  10.1016/s0014-827x(01)01121-1
• 作为产物：
  描述：

  盐酸小檗碱 在 sodium tetrahydroborate 、 水 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以89%的产率得到tetrahydroberberine hydrochloride
  参考文献：
  名称：

  Compounds and methods for modulating Rho GTPases

  摘要：

  本发明涉及影响Rho家族GTP酶的GTP结合活性的方法和组合物，优选是Rac GTP酶（Rac1、Raclb、Rac2和/或Rac3）。

  公开号：

  EP2014651A1

文献信息

• 盐酸去亚甲基四氢小檗碱晶型及其制备方法
  申请人：中国药科大学

  公开号：CN111808094B

  公开（公告）日：2022-03-11

  本发明属于药物化学技术领域，具体涉及盐酸去亚甲基四氢小檗碱的三种晶型A、B、C及其制备方法，本发明进一步提供了此三种晶型的X‑ray射线粉末衍射特征吸收峰，红外吸收峰以及DSC图谱。晶型X‑ray射线粉末衍射特征衍射峰约为6.264、9.603、10.622、11.933、12.338、13.206、15.011、15.409、17.879、18.273、18.569、18.844、19.223、19.865、20.174、21.348、21.742、22.393、23.280、24.699、26.133、26.700、27.180、27.630、28.419、29.088、31.801°。本发明还涉及三种盐酸去亚甲基四氢小檗碱晶型的制备方法。该制备方法工艺简单、收率高、成本低；产品纯度高、质量稳定。
• Improving solubility and avoiding hygroscopicity of tetrahydroberberine by forming hydrochloride salts by introducing solvents: [HTHB]Cl, [HTHB]Cl·CH₃OH and [HTHB]Cl·CH₃COOH
  作者：Yunan Zhang、Dajun Zhang、Yu Zhang、Lixin Liu、Xuesong Zhang、Lei Zhang、Yunjie Zhang、Liang Chang、Qiushuang Fan、Yongbiao Zhang、Jiaming Xi、Qiang Zhang

  DOI：10.1039/c7nj02423a

  日期：——

  With an aim to improve the solubility and dissolution rate of tetrahydroberberine (THB) by forming hydrochloride salts, three salts of THB, [HTHB]Cl (1), [HTHB]Cl•CH3OH (2) and [HTHB]Cl•CH3COOH (3), have been synthesized and characterized. The solubility and dissolution rate suggest the maximum solubility values for 1-3 are approximately 98, 47, and 43 times as large as that of THB, and dissolution

  为了通过形成盐酸盐来提高四氢小ber碱（THB）的溶解度和溶解速率，THB的三种盐分别为[HTHB] Cl（1），[HTHB] Cl•CH3OH（2）和[HTHB] Cl•CH3COOH（ 3），已合成并表征。溶解度和溶解度表明1-3的最大溶解度值约为THB的98、47和43倍，并且相对于THB，三种化合物的溶解度也得到了有效提高。令人惊讶的是，2和3的吸湿性已经比1的有效降低了，这表明通过将溶剂引入结构中可以成功地避免形成盐酸盐的吸湿性。对结构与性能之间关系的初步分析表明，由于2和3中存在溶剂，氯离子吸收水分子的能力（主要是通过氢键相互作用）降低了。避免吸湿性而不损害吸湿性API溶解度的一种鼓舞人心的方法。另外，与它们相应的母体化合物相比，这三种化合物在抗菌性能方面显示出优势。
• COMPOUNDS AND METHODS FOR MODULATING RHO GTPASES
  申请人：Leblond Bertrand

  公开号：US20100120810A1

  公开（公告）日：2010-05-13

  The present invention relates to methods and compositions that affect the GTP-binding activity of members of the Rho family GTPases, preferably Rac GTPases (Rac1, Rac1b, Rac2 and/or Rac3).

  本发明涉及影响Rho家族GTP酶成员的GTP结合活性的方法和组合物，优选是Rac GTP酶（Rac1，Rac1b，Rac2和/或Rac3）。
• Structure–activity relationship of isoform selective inhibitors of Rac1/1b GTPase nucleotide binding
  作者：Eric Beausoleil、Cédric Chauvignac、Thierry Taverne、Sandrine Lacombe、Laure Pognante、Bertrand Leblond、Diego Pallares、Catherine De Oliveira、Florence Bachelot、Rachel Carton、Hélène Peillon、Séverine Coutadeur、Virginie Picard、Nathalie Lambeng、Laurent Désiré、Fabien Schweighoffer

  DOI：10.1016/j.bmcl.2009.08.037

  日期：2009.10

  The synthesis of a series of berberine, phenantridine and isoquinoline derivatives was realized to explore their Rho GTPase nucleotide inhibitory activity. The compounds were evaluated in a nucleotide binding competition assay against Rac1, Rac1b, Cdc42 and in a cellular Rac GTPase activation assay. The insertion of 19 AA in the splice variant Rac1b is shown to be sufficient to introduce a conformational difference that allows compounds 4, 21, 22, and 26 to exhibit selective inhibition of Rac 1b over Rac1. (C) 2009 Elsevier Ltd. All rights reserved.
• [EN] COMPOUNDS AND METHODS FOR MODULATING RHO GTPASES<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR MODULER LES GTPASES RHO
  申请人：EXONHIT THERAPEUTICS SA

  公开号：WO2009007457A2

  公开（公告）日：2009-01-15

  The present invention relates to methods and compositions that affect the GTP-binding activity of members of the Rho family GTPases, preferably Rac GTPases (Rac1, Rac1b, Rac2 and/or Rac3).